A multicenter randomised controlled trial of hydroxyurea (hydroxycarbamide) in very young children with sickle cell anaemia

PubMed Central

Wang, Winfred C; Ware, Russell E; Miller, Scott T; Iyer, Rathi V; Casella, James F; Minniti, Caterina P; Rana, Sohail; Thornburg, Courtney D; Rogers, Zora R; Kalpatthi, Ram V; Barredo, Julio C; Brown, R Clark; Sarnaik, Sharada A; Howard, Thomas H; Wynn, Lynn W; Kutlar, Abdullah; Armstrong, F Daniel; Files, Beatrice A; Goldsmith, Jonathan C; Waclawiw, Myron A; Huang, Xiangke; Thompson, Bruce W

2011-01-01

Background Sickle cell anaemia (SCA) is associated with significant morbidity from acute complications and organ dysfunction beginning in the first year of life. In the first multicenter randomised double-blinded trial in very young children with SCA, the impact of hydroxyurea (hydroxycarbamide) therapy on organ dysfunction, clinical complications, and laboratory findings, and its toxicity, were examined. Methods Eligible subjects had HbSS or Sβ0thalassaemia, were age 9–18 months at randomisation, and were not selected for clinical severity. Subjects received liquid hydroxyurea, 20 mg/kg/day, or placebo for two years. Primary study endpoints were splenic function (qualitative uptake on 99Tc spleen scan) and renal function (glomerular filtration rate by 99mTc-DTPA clearance). Additional evaluations included: blood counts, HbF, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every two to four weeks. Findings Ninety-six subjects received hydroxyurea and 97 placebo; 86% completed the study. Significant differences were not seen for the primary endpoints, but suggestive benefit was noted in quantitative measures of spleen function. Hydroxyurea significantly decreased pain and dactylitis with trends for decreased acute chest syndrome, hospitalisation and transfusion. Hydroxyurea increased haemoglobin and HbF and decreased WBC count. Toxicity was limited to mild-moderate neutropaenia. Interpretation Although hydroxyurea treatment did not reduce splenic and renal dysfunction assessed by primary endpoint measures, it resulted in major clinical benefit because of diminished acute complications, favorable haematologic results, and a lack of unexpected toxicities. Based on the safety and efficacy data from this trial, hydroxyurea can now be considered for all very young children with SCA. PMID:21571150

CE verbal episodic memory impairment in schizophrenia: a comparison with frontal lobe lesion patients.

PubMed

Christensen, Bruce K; Patrick, Regan E; Stuss, Donald T; Gillingham, Susan; Zipursky, Robert B

2013-01-01

Schizophrenia (SCZ)-related verbal memory impairment is hypothesized to be mediated, in part, by frontal lobe (FTL) dysfunction. However, little research has contrasted the performance of SCZ patients with that of patients exhibiting circumscribed frontal lesions. The current study compared verbal episodic memory in patients with SCZ and focal FTL lesions (left frontal, LF; right frontal, RF; and bi-frontal, BF) on a four-trial list learning task consisting of three lists of varying semantic organizational structure. Each dependent variable was examined at two levels: scores collapsed across all four trials and learning scores (i.e., trial 4-trial 1). Performance deficits were observed in each patient group across most dependent measures at both levels. Regarding patient group differences, SCZ patients outperformed LF/BF patients (i.e., either learning scores or scores collapsed across trial) on free recall, primacy, primary memory, secondary memory, and subjective organization, whereas they only outperformed RF patients on the semantically blocked list on recency and primary memory. Collectively, these results indicate that the pattern of memory performance is largely similar between patients with SCZ and those with RF lesions. These data support tentative arguments that verbal episodic memory deficits in SCZ may be mediated by frontal dysfunction in the right hemisphere.

Sexual counselling for treating or preventing sexual dysfunction in women living with female genital mutilation: A systematic review.

PubMed

Okomo, Uduak; Ogugbue, Miriam; Inyang, Elizabeth; Meremikwu, Martin M

2017-02-01

Female sexual dysfunction is the persistent or recurring decrease in sexual desire or arousal, the difficulty or inability to achieve an orgasm, and/or the feeling of pain during sexual intercourse. Impaired sexual function can occur with all types of female genital mutilation (FGM) owing to the structural changes, pain, or traumatic memories associated with the procedure. To conduct a systematic review of randomized and nonrandomized studies into the effects of sexual counseling with or without genital lubricants on the sexual function of women living with FGM. Cochrane Central Register of Controlled Trials, MEDLINE, African Index Medicus, SCOPUS, LILACS, CINAHL, ClinicalTrials.gov, Pan African Clinical Trials Registry, and other databases were searched to August 2015. The reference lists of retrieved studies were checked for reports of additional studies, and lead authors contacted for additional data. Studies of girls and women living with any type of FGM who received counselling interventions for sexual dysfunction were included. No relevant studies that addressed the objective of the review were identified. Despite a comprehensive search, the authors could not find evidence of the effects of sexual counseling on the sexual function of women living with FGM. Studies assessing this intervention are needed. CRD42015024593. © 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

Transfusion Requirement in Burn Care Evaluation (TRIBE): A Multicenter Randomized Prospective Trial of Blood Transfusion in Major Burn Injury.

PubMed

Palmieri, Tina L; Holmes, James H; Arnoldo, Brett; Peck, Michael; Potenza, Bruce; Cochran, Amalia; King, Booker T; Dominic, William; Cartotto, Robert; Bhavsar, Dhaval; Kemalyan, Nathan; Tredget, Edward; Stapelberg, Francois; Mozingo, David; Friedman, Bruce; Greenhalgh, David G; Taylor, Sandra L; Pollock, Brad H

2017-10-01

Our objective was to compare outcomes of a restrictive to a liberal red cell transfusion strategy in 20% or more total body surface area (TBSA) burn patients. We hypothesized that the restrictive group would have less blood stream infection (BSI), organ dysfunction, and mortality. Patients with major burns have major (>1 blood volume) transfusion requirements. Studies suggest that a restrictive blood transfusion strategy is equivalent to a liberal strategy. However, major burn injury is precluded from these studies. The optimal transfusion strategy in major burn injury is thus needed but remains unknown. This prospective randomized multicenter trial block randomized patients to a restrictive (hemoglobin 7-8 g/dL) or liberal (hemoglobin 10-11 g/dL) transfusion strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. Eighteen burn centers enrolled 345 patients with 20% or more TBSA burn similar in age, TBSA burn, and inhalation injury. A total of 7054 units blood were transfused. The restrictive group received fewer blood transfusions: mean 20.3 ± 32.7 units, median = 8 (interquartile range: 3, 24) versus mean 31.8 ± 44.3 units, median = 16 (interquartile range: 7, 40) in the liberal group (P < 0.0001, Wilcoxon rank sum). BSI incidence, organ dysfunction, ventilator days, and time to wound healing (P > 0.05) were similar. In addition, there was no 30-day mortality difference: 9.5% restrictive versus 8.5% liberal (P = 0.892, χ test). A restrictive transfusion strategy halved blood product utilization. Although the restrictive strategy did not decrease BSI, mortality, or organ dysfunction in major burn injury, these outcomes were no worse than the liberal strategy (Clinicaltrials.gov identifier NCT01079247).

Oral disease profiles in chronic graft versus host disease.

PubMed

Bassim, C W; Fassil, H; Mays, J W; Edwards, D; Baird, K; Steinberg, S M; Cowen, E W; Naik, H; Datiles, M; Stratton, P; Gress, R E; Pavletic, S Z

2015-04-01

At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials. © International & American Associations for Dental Research 2015.

Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial.

PubMed

de Azevedo, Rodrigo Palacio; Freitas, Flávio Geraldo Resende; Ferreira, Elaine Maria; Pontes de Azevedo, Luciano Cesar; Machado, Flávia Ribeiro

2015-09-16

Constipation is a common problem in intensive care units. We assessed the efficacy and safety of laxative therapy aiming to promote daily defecation in reducing organ dysfunction in mechanically ventilated patients. We conducted a prospective, randomized, controlled, nonblinded phase II clinical trial at two general intensive care units. Patients expected to remain ventilated for over 3 days were randomly assigned to daily defecation or control groups. The intervention group received lactulose and enemas to produce 1-2 defecations per day. In the control group, absence of defecation was tolerated up to 5 days. Primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score between the date of enrollment and intensive care unit discharge, death or day 14. We included 88 patients. Patients in the treatment group had a higher number of defecations per day (1.3 ± 0.42 versus 0.7 ± 0.56, p < 0.0001) and lower percentage of days without defecation (33.1 ± 15.7% versus 62.3 ± 24.5%, p < 0.0001). Patients in the intervention group had a greater reduction in SOFA score (-4.0 (-6.0 to 0) versus -1.0 (-4.0 to 1.0), p = 0.036) with no difference in mortality rates or in survival time. Adverse events were more frequent in the treatment group (4.5 (3.0-8.0) versus 3.0 (1.0-5.7), p = 0.016), including more days with diarrhea (2.0 (1.0-4.0) versus 1.0 (0-2.0) days, p < 0.0001). Serious adverse events were rare and did not significantly differ between groups. Laxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score. Clinical Trials.gov NCT01607060, registered 24 May 2012.

Systemic Inflammatory Response Syndrome, Quick Sequential Organ Function Assessment, and Organ Dysfunction: Insights From a Prospective Database of ED Patients With Infection.

PubMed

Williams, Julian M; Greenslade, Jaimi H; McKenzie, Juliet V; Chu, Kevin; Brown, Anthony F T; Lipman, Jeffrey

2017-03-01

A proposed revision of sepsis definitions has abandoned the systemic inflammatory response syndrome (SIRS), defined organ dysfunction as an increase in total Sequential Organ Function Assessment (SOFA) score of ≥ 2, and conceived "qSOFA" (quick SOFA) as a bedside indicator of organ dysfunction. We aimed to (1) determine the prognostic impact of SIRS, (2) compare the diagnostic accuracy of SIRS and qSOFA for organ dysfunction, and (3) compare standard (Sepsis-2) and revised (Sepsis-3) definitions for organ dysfunction in ED patients with infection. Consecutive ED patients admitted with presumed infection were prospectively enrolled over 3 years. Sufficient observational data were collected to calculate SIRS, qSOFA, SOFA, comorbidity, and mortality. We enrolled 8,871 patients, with SIRS present in 4,176 (47.1%). SIRS was associated with increased risk of organ dysfunction (relative risk [RR] 3.5) and mortality in patients without organ dysfunction (OR 3.2). SIRS and qSOFA showed similar discrimination for organ dysfunction (area under the receiver operating characteristic curve, 0.72 vs 0.73). qSOFA was specific but poorly sensitive for organ dysfunction (96.1% and 29.7%, respectively). Mortality for patients with organ dysfunction was similar for Sepsis-2 and Sepsis-3 (12.5% and 11.4%, respectively), although 29% of patients with Sepsis-3 organ dysfunction did not meet Sepsis-2 criteria. Increasing numbers of Sepsis-2 organ system dysfunctions were associated with greater mortality. SIRS was associated with organ dysfunction and mortality, and abandoning the concept appears premature. A qSOFA score ≥ 2 showed high specificity, but poor sensitivity may limit utility as a bedside screening method. Although mortality for organ dysfunction was comparable between Sepsis-2 and Sepsis-3, more prognostic and clinical information is conveyed using Sepsis-2 regarding number and type of organ dysfunctions. The SOFA score may require recalibration. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Role of the microbiome, probiotics, and 'dysbiosis therapy' in critical illness.

PubMed

Wischmeyer, Paul E; McDonald, Daniel; Knight, Rob

2016-08-01

Loss of 'health-promoting' microbes and overgrowth of pathogenic bacteria (dysbiosis) in ICU is believed to contribute to nosocomial infections, sepsis, and organ failure (multiple organ dysfunction syndrome). This review discusses new understanding of ICU dysbiosis, new data for probiotics and fecal transplantation in ICU, and new data characterizing the ICU microbiome. ICU dysbiosis results from many factors, including ubiquitous antibiotic use and overuse. Despite advances in antibiotic therapy, infections and mortality from often multidrug-resistant organisms (i.e., Clostridium difficile) are increasing. This raises the question of whether restoration of a healthy microbiome via probiotics or other 'dysbiosis therapies' would be an optimal alternative, or parallel treatment option, to antibiotics. Recent clinical data demonstrate probiotics can reduce ICU infections and probiotics or fecal microbial transplant (FMT) can treat Clostridium difficile. This contributes to recommendations that probiotics should be considered to prevent infection in ICU. Unfortunately, significant clinical variability limits the strength of current recommendations and further large clinical trials of probiotics and FMT are needed. Before larger trials of 'dysbiosis therapy' can be thoughtfully undertaken, further characterization of ICU dysbiosis is needed. To addressing this, we conducted an initial analysis demonstrating a rapid and marked change from a 'healthy' microbiome to an often pathogen-dominant microbiota (dysbiosis) in a broad ICU population. A growing body of evidence suggests critical illness and ubiquitous antibiotic use leads to ICU dysbiosis that is associated with increased ICU infection, sepsis, and multiple organ dysfunction syndrome. Probiotics and FMT show promise as ICU therapies for infection. We hope future-targeted therapies using microbiome signatures can be developed to correct 'illness-promoting' dysbiosis to restore a healthy microbiome post-ICU to improve patient outcomes.

Milrinone for cardiac dysfunction in critically ill adult patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.

PubMed

Koster, Geert; Bekema, Hanneke J; Wetterslev, Jørn; Gluud, Christian; Keus, Frederik; van der Horst, Iwan C C

2016-09-01

Milrinone is an inotrope widely used for treatment of cardiac failure. Because previous meta-analyses had methodological flaws, we decided to conduct a systematic review of the effect of milrinone in critically ill adult patients with cardiac dysfunction. This systematic review was performed according to The Cochrane Handbook for Systematic Reviews of Interventions. Searches were conducted until November 2015. Patients with cardiac dysfunction were included. The primary outcome was serious adverse events (SAE) including mortality at maximum follow-up. The risk of bias was evaluated and trial sequential analyses were conducted. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation criteria. A total of 31 randomised clinical trials fulfilled the inclusion criteria, of which 16 provided data for our analyses. All trials were at high risk of bias, and none reported the primary composite outcome SAE. Fourteen trials with 1611 randomised patients reported mortality data at maximum follow-up (RR 0.96; 95% confidence interval 0.76-1.21). Milrinone did not significantly affect other patient-centred outcomes. All analyses displayed statistical and/or clinical heterogeneity of patients, interventions, comparators, outcomes, and/or settings and all featured missing data. The current evidence on the use of milrinone in critically ill adult patients with cardiac dysfunction suffers from considerable risks of both bias and random error and demonstrates no benefits. The use of milrinone for the treatment of critically ill patients with cardiac dysfunction can be neither recommended nor refuted. Future randomised clinical trials need to be sufficiently large and designed to have low risk of bias.

Pirfenidone: an anti-fibrotic and cytoprotective agent as therapy for progressive kidney disease

PubMed Central

Cho, Monique E; Kopp, Jeffrey B

2010-01-01

Importance of the field Many chronic diseases of various etiologies universally lead to fibrosis and organ dysfunction. Despite many advances in medicine in recent years, options to slow the progression of fibrotic diseases have remained limited. The recent availability of pirfenidone, an anti-fibrotic and anti-inflammatory investigational agent, thus offers a new hope for treating progressive fibrotic diseases. Areas covered in this review This review provides concise review of the available data regarding mechanism and pharmacokinetics of pirfenidone and preclinical and clinical data regarding efficacy and safety in fibrotic diseases of the kidney. It also reviews results of clinical trials involving pirfenidone in other fibrotic diseases. What the reader will gain The review will provide in-depth review of pirfenidone with a renal focus. Take home message Because many of the available clinical trials have been small and/or uncontrolled, conclusive evidence regarding efficacy and safety of pirfenidone is lacking, particularly in patients with renal or hepatic dysfunction. Larger studies are needed both to better understand long-term efficacy and safety of this medication in various patient populations. PMID:20050822

Psychogenic erectile dysfunction.

PubMed

Bodie, Joshua A; Beeman, William W; Monga, Manoj

2003-01-01

To educate healthcare professionals on the historical aspects, clinical diagnosis, and current treatment methods of psychogenic erectile dysfunction. A topic review of current literature was performed. Chief sources included primarily mainstream journals in the fields of urology, psychiatry/psychology, impotence/erectile dysfunction, epidemiology, and internal medicine. MEDLINE and PsycINFO databases were utilized. Data from clinical studies, trials, and review articles concerned primarily with psychological aspects of the arousal (erectile function) phase of the male sexual response cycle were collected, analyzed, and summarized in this review article. There has been a shift in how erectile dysfunction has been perceived and treated over the past 30 years. With the current focus now on the very prevalent organic causes of ED, psychological factors are increasingly overlooked, though they remain important to the treatment of the patient as a whole. This article provides a complete, concise review of the interplay between psychological components and erectile function, reviews the work-up and diagnosis of psychogenic ED, and discusses treatment methods. Erectile dysfunction is a prevalent problem that can affect, and can be affected by, psychosocial aspects of a man's life. Medical or pharmacological interventions are often appropriate to treat ED, but the psychosocial aspects should not be ignored. It has become easier for practitioners to put aside patients' psychosocial and interpersonal concerns regarding sexual health. Clinicians provide the best possible treatment if they recognize that erectile dysfunction is a complex, multifactorial disorder, and treat accordingly.

Number of organ dysfunctions predicts mortality in emergency department patients with suspected infection: a multicenter validation study.

PubMed

Jessen, Marie K; Skibsted, Simon; Shapiro, Nathan I

2017-06-01

The aim of this study was to validate the association between number of organ dysfunctions and mortality in emergency department (ED) patients with suspected infection. This study was conducted at two medical care center EDs. The internal validation set was a prospective cohort study conducted in Boston, USA. The external validation set was a retrospective case-control study conducted in Aarhus, Denmark. The study included adult patients (>18 years) with clinically suspected infection. Laboratory results and clinical data were used to assess organ dysfunctions. Inhospital mortality was the outcome measure. Multivariate logistic regression was used to determine the independent mortality odds for number and types of organ dysfunctions. We enrolled 4952 (internal) and 483 (external) patients. The mortality rate significantly increased with increasing number of organ dysfunctions: internal validation: 0 organ dysfunctions: 0.5% mortality, 1: 3.6%, 2: 9.5%, 3: 17%, and 4 or more: 37%; external validation: 2.2, 6.7, 17, 41, and 57% mortality (both P<0.001 for trend). Age-adjusted and comorbidity-adjusted number of organ dysfunctions remained an independent predictor. The effect of specific types of organ dysfunction on mortality was most pronounced for hematologic [odds ratio (OR) 3.3 (95% confidence interval (CI) 2.0-5.4)], metabolic [OR 3.3 (95% CI 2.4-4.6); internal validation], and cardiovascular dysfunctions [OR 14 (95% CI 3.7-50); external validation]. The number of organ dysfunctions predicts sepsis mortality.

Comparing the effects of treatment with sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women: a randomized controlled clinical trial

PubMed Central

Omidi, Abdollah; Ahmadvand, Afshin; Najarzadegan, Mohammad Reza; Mehrzad, Fateme

2016-01-01

Background Sexual dysfunction in women is prevalent and common in women after menopause. Many attempts to treat patients with sexual dysfunction by cognitive-behavioral therapy (CBT) methods. But to the best of our knowledge, there has been no study that compared these two methods. Objective The aim of this study was to assess and compare the effects of sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women. Methods In this randomized, controlled, clinical trial, 86 women with arousal and orgasm dysfunction were surveyed. The patients were divided into two groups, i.e., sildenafil and CBT groups. The patients in the sildenafil group were treated by 50 mg of oral sildenafil one hour before intercourse, and the other group had weekly sessions of CBT for eight weeks. Sexual dysfunctions were evaluated by the Female Sexual Function Index (FSFI), a sexual satisfaction questionnaire, and the Enrich marital satisfaction scale. Results The mean age of the participants was 33.14 ± 7.34 years. The mean scores for female sexual function index, sexual satisfaction, and the Enrich marital satisfaction scale were increased in both groups during treatment (p < 0.001). It was found that cognitive-behavioral therapy compared to treatment with sildenafil increased all subscales, except arousal, orgasm, and lubrication. Conclusion Cognitive-behavioral therapy is more effective than treatment with sildenafil for improving female sexual function. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2014070318338N1. Funding The authors received no financial support for the research, authorship, and/or publication of this article. PMID:27382439

Lactate Clearance and Normalization and Prolonged Organ Dysfunction in Pediatric Sepsis.

PubMed

Scott, Halden F; Brou, Lina; Deakyne, Sara J; Fairclough, Diane L; Kempe, Allison; Bajaj, Lalit

2016-03-01

To evaluate whether lactate clearance and normalization during emergency care of pediatric sepsis is associated with lower rates of persistent organ dysfunction. This was a prospective cohort study of 77 children <18 years of age in the emergency department with infection and acute organ dysfunction per consensus definitions. In consented patients, lactate was measured 2 and/or 4 hours after an initial lactate; persistent organ dysfunction was assessed through laboratory and physician evaluation at 48 hours. A decrease of ≥ 10% from initial to final level was considered lactate clearance; a final level < 2 mmol/L was considered lactate normalization. Relative risk (RR) with 95% CIs, adjusted in a log-binomial model, was used to evaluate associations between lactate clearance/normalization and organ dysfunction. Lactate normalized in 62 (81%) patients and cleared in 70 (91%). The primary outcome, persistent 48-hour organ dysfunction, was present in 32 (42%). Lactate normalization was associated with decreased risk of persistent organ dysfunction (RR 0.46, 0.29-0.73; adjusted RR 0.47, 0.29-0.78); lactate clearance was not (RR 0.70, 0.35-1.41; adjusted RR 0.75, 0.38-1.50). The association between lactate normalization and decreased risk of persistent organ dysfunction was retained in the subgroups with initial lactate ≥ 2 mmol/L and hypotension. In children with sepsis and organ dysfunction, lactate normalization within 4 hours was associated with decreased persistent organ dysfunction. Serial lactate level measurement may provide a useful prognostic tool during the first hours of resuscitation in pediatric sepsis. Copyright © 2016 Elsevier Inc. All rights reserved.

Specific Etiologies Associated With the Multiple Organ Dysfunction Syndrome in Children: Part 2.

PubMed

Upperman, Jeffrey S; Bucuvalas, John C; Williams, Felicia N; Cairns, Bruce A; Cox, Charles S; Doctor, Allan; Tamburro, Robert F

2017-03-01

To describe a number of conditions and therapies associated with multiple organ dysfunction syndrome presented as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Multiple Organ Dysfunction Workshop (March 26-27, 2015). In addition, the relationship between burn injuries and multiple organ dysfunction syndrome is also included although it was not discussed at the workshop. Literature review, research data, and expert opinion. Not applicable. Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions and therapies were presented, discussed, and debated with a focus on identifying knowledge gaps and the research priorities. Summary of presentations and discussion supported and supplemented by relevant literature. Sepsis and trauma are the two conditions most commonly associated with multiple organ dysfunction syndrome both in children and adults. However, many other pathophysiologic processes may result in multiple organ dysfunction syndrome. In this article, we discuss conditions such as liver failure and pancreatitis, pathophysiologic processes such as ischemia and hypoxia, and injuries such as trauma and burns. Additionally, therapeutic interventions such as medications, blood transfusions, transplantation may also precipitate and contribute to multiple organ dysfunction syndrome. The purpose of this article is to describe the association of multiple organ dysfunction syndrome with a variety of conditions and therapies in an attempt to identify similarities, differences, and opportunities for therapeutic intervention.

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.

The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial.

PubMed

Stevanovic, Ana; Coburn, Mark; Menon, Ares; Rossaint, Rolf; Heyland, Daren; Schälte, Gereon; Werker, Thilo; Wonisch, Willibald; Kiehntopf, Michael; Goetzenich, Andreas; Rex, Steffen; Stoppe, Christian

2014-01-01

Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress. In this prospective randomised, interventional trial, 40 patients scheduled for elective coronary artery bypass grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if both techniques were feasible for the single patient. Clinical data, myocardial damage assessed by myocard specific creatine kinase isoenzyme (CK-MB), circulating whole blood levels of selenium, oxidative stress assessed by asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by glutathionperoxidase (GPx) levels and perioperative inflammation represented by interleukin-6 (IL-6) levels were measured at predefined perioperative time points. At end of surgery, both groups showed a comparable decrease of circulating selenium concentrations. Likewise, levels of oxidative stress and IL-6 were comparable in both groups. Selenium levels correlated with antioxidant capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to myocardial damage (CK-MB: r =  -0.571, p<0.001). Low postoperative selenium levels had a high predictive value for the occurrence of any postoperative complication. OPCAB surgery is not associated with less oxidative stress and a better preservation of the circulating selenium pool than on-pump surgery. Low postoperative selenium levels are predictive for the development of complications. ClinicalTrials.gov NCT01409057.

Ezetimibe in Combination With Statins Ameliorates Endothelial Dysfunction in Coronary Arteries After Stenting: The CuVIC Trial (Effect of Cholesterol Absorption Inhibitor Usage on Target Vessel Dysfunction After Coronary Stenting), a Multicenter Randomized Controlled Trial.

PubMed

Takase, Susumu; Matoba, Tetsuya; Nakashiro, Soichi; Mukai, Yasushi; Inoue, Shujiro; Oi, Keiji; Higo, Taiki; Katsuki, Shunsuke; Takemoto, Masao; Suematsu, Nobuhiro; Eshima, Kenichi; Miyata, Kenji; Yamamoto, Mitsutaka; Usui, Makoto; Sadamatsu, Kenji; Satoh, Shinji; Kadokami, Toshiaki; Hironaga, Kiyoshi; Ichi, Ikuyo; Todaka, Koji; Kishimoto, Junji; Egashira, Kensuke; Sunagawa, Kenji

2017-02-01

We sought to investigate whether treatment with ezetimibe in combination with statins improves coronary endothelial function in target vessels in coronary artery disease patients after coronary stenting. We conducted a multicenter, prospective, randomized, open-label, blinded-end point trial among 11 cardiovascular treatment centers. From 2011 to 2013, 260 coronary artery disease patients who underwent coronary stenting were randomly allocated to 2 arms (statin monotherapy, S versus ezetimibe [10 mg/d]+statin combinational therapy, E+S). We defined target vessel dysfunction as the primary composite outcome, which comprised target vessel failure during treatment and at the 6- to 8-month follow-up coronary angiography and coronary endothelial dysfunction determined via intracoronary acetylcholine testing performed in cases without target vessel failure at the follow-up coronary angiography. Coadministration of ezetimibe with statins further lowered low-density lipoprotein cholesterol levels (83±23 mg/dL in S versus 67±23 mg/dL in E+S; P<0.0001), with significant decreases in oxidized low-density lipoprotein and oxysterol levels. Among patients without target vessel failure, 46 out of 89 patients (52%) in the S arm and 34 out of 96 patients (35%) in the E+S arm were found to have coronary endothelial dysfunction (P=0.0256), and the incidence of target vessel dysfunction at follow-up was significantly decreased in the E+S arm (69/112 (62%) in S versus 47/109 (43%) in E+S; P=0.0059). A post hoc analysis of post-treatment low-density lipoprotein cholesterol-matched subgroups revealed that the incidence of both target vessel dysfunction and coronary endothelial dysfunction significantly decreased in the E+S arm, with significant reductions in oxysterol levels. The CuVIC trial (Effect of Cholesterol Absorption Inhibitor Usage on Target Vessel Dysfunction after Coronary Stenting) has shown that ezetimibe with statins, compared with statin monotherapy, improves functional prognoses, ameliorating endothelial dysfunction in stented coronary arteries, and was associated with larger decreases in oxysterol levels. © 2016 American Heart Association, Inc.

The effects of aging on conflict detection.

PubMed

Lucci, Giuliana; Berchicci, Marika; Spinelli, Donatella; Taddei, Francesco; Di Russo, Francesco

2013-01-01

Several cognitive changes characterize normal aging; one change regards inhibitory processing and includes both conflict monitoring and response suppression. We attempted to segregate these two aspects within a Go/No-go task, investigating three age categories. Accuracy, response times and event-related potentials (ERPs) were recorded. The ERP data were analyzed, and the Go and No-go trials were separated; in addition, the trials were organized in repeat trials (in which the subjects repeated the action delivered in the previous trial) and switch trials (in which the subjects produced a response opposite to the previous response). We assumed that the switch trials conveyed more conflict than the repeat trials. In general, the behavioral data and slower P3 latencies confirmed the well-known age-related speed/accuracy trade-off. The novel analyses of the repeat vs. switch trials indicated that the age-related P3 slowing was significant only for the high conflict condition; the switch-P3 amplitude increased only in the two older groups. The 'aging switch effect' on the P3 component suggests a failure in the conflict conditions and likely contributes to a generalized dysfunction. The absence of either a switch effect in the young group and the P3 slowing in middle-aged group indicate that switching was not particularly demanding for these participants. The N2 component was less sensitive to the repeat/switch manipulation; however, the subtractive waves also enhanced the age effects in this earlier time window. The topographic maps showed other notable age effects: the frontal No-go N2 was nearly undetectable in the elderly; in the identical time window, a large activity in the posterior and prefrontal scalp regions was observed. Moreover, the prefrontal activity showed a negative correlation with false alarms. These results suggest that the frontal involvement during action suppression becomes progressively dysfunctional with aging, and additional activity was required to reach a good level of accuracy.

Stabilisation splint therapy for temporomandibular pain dysfunction syndrome.

PubMed

Al-Ani, M Z; Davies, S J; Gray, R J M; Sloan, P; Glenny, A M

2004-01-01

Pain dysfunction syndrome (PDS) is the most common temporomandibular disorder (TMD). There are many synonyms for this condition including facial arthromylagia, TMJ dysfunction syndrome, myofacial pain dysfunction syndrome, craniomandibular dysfunction and myofacial pain dysfunction. The aetiology of PDS is multifactorial and many different therapies have been advocated. To establish the effectiveness of stabilisation splint therapy in reducing symptoms in patients with pain dysfunction syndrome. Electronic databases (including the Cochrane Oral Health Group's Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); The Cochrane Library Issue 2, 2003; MEDLINE (1966 to June 2001); EMBASE (1966 to June 2001)) were searched. Handsearching of relevant journals was undertaken and reference lists of included studies screened. Experts in the field were contacted to identify unpublished articles. There was no language restriction. Randomised or quasi-randomised controlled trials (RCTs), in which splint therapy was compared concurrently to no treatment, other occlusal appliances, or any other active intervention. Data extraction was carried out independently and in duplicate. Validity assessment of the included trials was carried out at the same time as data extraction. Discrepancies were discussed and a third reviewer consulted. The author of the primary study was contacted where necessary. The studies were grouped according to treatment type and duration of follow up. Twenty potentially relevant RCTs were identified. Eight trials were excluded leaving 12 RCTs for analysis. Stabilisation splint therapy was compared to: acupuncture, bite plates, biofeedback/stress management, visual feedback, relaxation, jaw exercises, non-occluding appliance and minimal/no treatment. There was no evidence of a statistically significant difference in the effectiveness of stabilisation splint therapy (SS) in reducing symptoms in patients with pain dysfunction syndrome compared with other active treatments. There is weak evidence to suggest that the use of SS for the treatment of PDS may be beneficial for reducing pain severity, at rest and on palpation, when compared to no treatment. There is insufficient evidence either for or against the use of stabilisation splint therapy for the treatment of temporomandibular pain dysfunction syndrome. This review suggests the need for further, well conducted RCTs that pay attention to method of allocation, outcome assessment, large sample size, and enough duration of follow up. A standardisation of the outcomes of the treatment of PDS should be established in the RCTs.

Standards for Clinical Trials in Male and Female Sexual Dysfunction: II. Patient-Reported Outcome Measures.

PubMed

Fisher, William A; Gruenwald, Ilan; Jannini, Emmanuele A; Lev-Sagie, Ahinoam; Lowenstein, Lior; Pyke, Robert E; Reisman, Yakov; Revicki, Dennis A; Rubio-Aurioles, Eusebio

2016-12-01

The second article in this series, Standards for Clinical Trials in Male and Female Sexual Dysfunction, focuses on measurement of patient-reported outcomes (PROs). Together with the design of appropriate phase I to phase IV clinical trials, the development, validation, choice, and implementation of valid PRO measurements-the focus of the present article-form the foundation of research on treatments for male and female sexual dysfunctions. PRO measurements are assessments of any aspect of a patient's health status that come directly from the patient (ie, without the interpretation of the patient's responses by a physician or anyone else). PROs are essential for assessing male and female sexual dysfunction and treatment response, including symptom frequency and severity, personal distress, satisfaction, and other measurements of sexual and general health-related quality of life. Although there are some relatively objective measurements of sexual dysfunction (ie, intravaginal ejaculatory latency time, frequency of sexual activity, etc), these measurements do not comprehensively assess the occurrence and extent of sexual dysfunction or treatment on the patient's symptoms, functioning, and well-being. Data generated by a PRO instrument can provide evidence of a treatment benefit from the patient's perspective. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up.

PubMed

Meybohm, Patrick; Kohlhaas, Madeline; Stoppe, Christian; Gruenewald, Matthias; Renner, Jochen; Bein, Berthold; Albrecht, Martin; Cremer, Jochen; Coburn, Mark; Schaelte, Gereon; Boening, Andreas; Niemann, Bernd; Sander, Michael; Roesner, Jan; Kletzin, Frank; Mutlak, Haitham; Westphal, Sabine; Laufenberg-Feldmann, Rita; Ferner, Marion; Brandes, Ivo F; Bauer, Martin; Stehr, Sebastian N; Kortgen, Andreas; Wittmann, Maria; Baumgarten, Georg; Meyer-Treschan, Tanja; Kienbaum, Peter; Heringlake, Matthias; Schoen, Julika; Treskatsch, Sascha; Smul, Thorsten; Wolwender, Ewa; Schilling, Thomas; Fuernau, Georg; Bogatsch, Holger; Brosteanu, Oana; Hasenclever, Dirk; Zacharowski, Kai

2018-03-26

Remote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham-RIPC. In this follow-up paper, we present 1-year follow-up of the composite primary end point and its individual components (all-cause mortality, myocardial infarction, stroke and acute renal failure), in a sub-group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1-year composite primary end point (RIPC versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively. Similar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long-term outcome in cardiac surgery patients undergoing propofol anesthesia. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Associations of Body Mass Index and Physical Activity With Sexual Dysfunction in Breast Cancer Survivors.

PubMed

Paiva, Carlos Eduardo; Rezende, Fabiana Faria; Paiva, Bianca Sakamoto Ribeiro; Mauad, Edmundo Carvalho; Zucca-Matthes, Gustavo; Carneseca, Estela Cristina; Syrjänen, Kari Juhani; Schover, Leslie R

2016-11-01

Sexual dysfunction is a common and distressing consequence of breast cancer (BC) treatment. In the present study, we investigated the sexual functioning of BC patients and its association with women's personal characteristics and cancer treatments. In this cross-sectional study, sexual function was assessed using the Female Sexual Function Index (FSFI). The health-related quality of life (HRQOL) was measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and its breast module BR-23. Of the 235 participants approached, 216 participants were included in the study. Of these, 63 patients reported no sexual activity in the last month and thus were analyzed only in relation to the sexual desire domain of FSFI. A total of 154 (71.3 %) patients were classified with hypoactive sexual desire disorder (HSDD). From those patients reporting sexual activity in the last month, 63.3 % (97 out of 153) were classified with sexual dysfunction. Using hierarchical logistic regression, the variance explained (change in R 2 ) by the addition of body mass index (BMI) and mild to moderate physical activity in the prediction models of sexual dysfunction and HSDD were 6.8 and 7.2 %, respectively. Age, BMI, and physical activity were independently associated with sexual dysfunction and HSDD. Additionally, BC patients with sexual dysfunction reported lower scores on global HRQOL, role functioning, and fatigue. Based on our findings, BC survivors should be encouraged to practice regular physical activity and to lose weight in order to avoid sexual dysfunction. However, future clinical trials are needed to confirm these findings.

Clinical trial tests drug for tumors associated with Krebs-cycle dysfunction | Center for Cancer Research

Cancer.gov

The Krebs cycle is part of the complex process where cells turn food into energy. One of the elements of the Krebs cycle is succinate dehydrogenase (SDH). Loss of SDH activity in cells has been linked to tumor formation. This new trial is studying guadecitabine for tumors associated with Krebs cycle dysfunction. Learn more...

Cabozantinib-induced thyroid dysfunction: a review of two ongoing trials for metastatic bladder cancer and sarcoma.

PubMed

Yavuz, Sahzene; Apolo, Andrea B; Kummar, Shivaani; del Rivero, Jaydira; Madan, Ravi A; Shawker, Thomas; Reynolds, James; Celi, Francesco S

2014-08-01

Thyroid dysfunction is a common adverse event associated with tyrosine kinase inhibitors (TKI), but its underlying pathophysiology is unclear. Cabozantinib is a novel TKI currently Food and Drug Administration approved for advanced medullary thyroid cancer and tested in clinical trials on solid tumors including prostate, liver, bladder, breast, and ovarian cancer. We analyzed the thyroid function of patients enrolled in two phase 2 clinical trials using cabozantinib at the National Institutes of Health Clinical Center. Two cases of thyroiditis associated with cabozantinib therapy are presented in detail, and a systematic review of the literature on TKI-associated thyroid dysfunction is also discussed. Between September 2012 and September 2013, 33 patients were treated with cabozantinib, and follow-up thyroid function tests were available for 31 (20 males, 11 females; age 59±1 years). Thyroid dysfunction was recorded in the majority of patients (93.1%), with a predominance of subclinical hypothyroidism. Two cases showed a biphasic pattern of thyroid dysfunction characterized by a transient thyrotoxicosis followed by hypothyroidism. Color Doppler demonstrated an increase in vascularization during the thyrotoxic phase, but no uptake was visualized on nuclear medicine imaging. A systematic review of the literature resulted in the identification of 40 original manuscripts, of which 13 were case series and 6 were case reports describing TKI-associated thyroid dysfunction. TKI therapy often results in clinically significant thyroid dysfunction. Cabozantinib treatment commonly results in thyroid dysfunction varying from subclinical hypothyroidism to symptomatic thyrotoxicosis. Early detection and characterization of cabozantinib-associated thyroid dysfunction and close follow-up are essential to provide adequate management of this common adverse event.

Cabozantinib-Induced Thyroid Dysfunction: A Review of Two Ongoing Trials for Metastatic Bladder Cancer and Sarcoma

PubMed Central

Yavuz, Sahzene; Apolo, Andrea B.; Kummar, Shivaani; del Rivero, Jaydira; Madan, Ravi A.; Shawker, Thomas; Reynolds, James

2014-01-01

Background: Thyroid dysfunction is a common adverse event associated with tyrosine kinase inhibitors (TKI), but its underlying pathophysiology is unclear. Cabozantinib is a novel TKI currently Food and Drug Administration approved for advanced medullary thyroid cancer and tested in clinical trials on solid tumors including prostate, liver, bladder, breast, and ovarian cancer. Methods: We analyzed the thyroid function of patients enrolled in two phase 2 clinical trials using cabozantinib at the National Institutes of Health Clinical Center. Two cases of thyroiditis associated with cabozantinib therapy are presented in detail, and a systematic review of the literature on TKI-associated thyroid dysfunction is also discussed. Results: Between September 2012 and September 2013, 33 patients were treated with cabozantinib, and follow-up thyroid function tests were available for 31 (20 males, 11 females; age 59±1 years). Thyroid dysfunction was recorded in the majority of patients (93.1%), with a predominance of subclinical hypothyroidism. Two cases showed a biphasic pattern of thyroid dysfunction characterized by a transient thyrotoxicosis followed by hypothyroidism. Color Doppler demonstrated an increase in vascularization during the thyrotoxic phase, but no uptake was visualized on nuclear medicine imaging. A systematic review of the literature resulted in the identification of 40 original manuscripts, of which 13 were case series and 6 were case reports describing TKI-associated thyroid dysfunction. Conclusion: TKI therapy often results in clinically significant thyroid dysfunction. Cabozantinib treatment commonly results in thyroid dysfunction varying from subclinical hypothyroidism to symptomatic thyrotoxicosis. Early detection and characterization of cabozantinib-associated thyroid dysfunction and close follow-up are essential to provide adequate management of this common adverse event. PMID:24724719

Performance of the PEdiatric Logistic Organ Dysfunction-2 score in critically ill children requiring plasma transfusions.

PubMed

Karam, Oliver; Demaret, Pierre; Duhamel, Alain; Shefler, Alison; Spinella, Philip C; Stanworth, Simon J; Tucci, Marisa; Leteurtre, Stéphane

2016-12-01

Organ dysfunction scores, based on physiological parameters, have been created to describe organ failure. In a general pediatric intensive care unit (PICU) population, the PEdiatric Logistic Organ Dysfunction-2 score (PELOD-2) score had both a good discrimination and calibration, allowing to describe the clinical outcome of critically ill children throughout their stay. This score is increasingly used in clinical trials in specific subpopulation. Our objective was to assess the performance of the PELOD-2 score in a subpopulation of critically ill children requiring plasma transfusions. This was an ancillary study of a prospective observational study on plasma transfusions over a 6-week period, in 101 PICUs in 21 countries. All critically ill children who received at least one plasma transfusion during the observation period were included. PELOD-2 scores were measured on days 1, 2, 5, 8, and 12 after plasma transfusion. Performance of the score was assessed by the determination of the discrimination (area under the ROC curve: AUC) and the calibration (Hosmer-Lemeshow test). Four hundred and forty-three patients were enrolled in the study (median age and weight: 1 year and 9.1 kg, respectively). Observed mortality rate was 26.9 % (119/443). For PELOD-2 on day 1, the AUC was 0.76 (95 % CI 0.71-0.81) and the Hosmer-Lemeshow test was p = 0.76. The serial evaluation of the changes in the daily PELOD-2 scores from day 1 demonstrated a significant association with death, adjusted for the PELOD-2 score on day 1. In a subpopulation of critically ill children requiring plasma transfusion, the PELOD-2 score has a lower but acceptable discrimination than in an entire population. This score should therefore be used cautiously in this specific subpopulation.

Psychological correlates of sexual dysfunction in female rectal and anal cancer survivors: analysis of baseline intervention data.

PubMed

Philip, Errol J; Nelson, Christian; Temple, Larissa; Carter, Jeanne; Schover, Leslie; Jennings, Sabrina; Jandorf, Lina; Starr, Tatiana; Baser, Ray; DuHamel, Katherine

2013-10-01

Sexual dysfunction represents a complex and multifactorial construct that can affect both men and women and has been noted to often deteriorate significantly after treatment for rectal and anal cancer. Despite this, it remains an understudied, underreported, and undertreated issue in the field of cancer survivorship. This study examined the characteristics of women enrolled in an intervention trial to treat sexual dysfunction, and explored the relationship between sexual functioning and psychological well-being. There were 70 female posttreatment anal or rectal cancer survivors assessed as part of the current study. Participants were enrolled in a randomized intervention trial to treat sexual dysfunction and completed outcome measures prior to randomization. The main outcome measures are quality of life (QOL) (European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire [EORTC-QLQ-C30] and Colorectal Cancer-Specific Module [QLQ-CR38]), sexual functioning (Female Sexual Functioning Index), and psychological well-being (Brief Symptom Inventory Depression/Anxiety, Impact of Events Scale-Revised, CR-38 Body Image). Women enrolled in the study intervention were on average 55 years old, predominantly Caucasian (79%), married (57%), and a median of 4 years postprimary treatment. For those reporting sexual activity at baseline (N=41), sexual dysfunction was associated with a range of specific measures of psychological well-being, all in the hypothesized direction. The Sexual/Relationship Satisfaction subscale was associated with all measures of psychological well-being (r=-0.45 to -0.70, all P<0.01). Body image, anxiety, and cancer-specific posttraumatic distress were notable in their association with subscales of sexual functioning, while a global QOL measure was largely unrelated. For sexually active female rectal and anal cancer survivors enrolled in a sexual health intervention, sexual dysfunction was significantly and consistently associated with specific measures of psychological well-being, most notably Sexual/Relationship Satisfaction. These results suggest that sexual functioning may require focused assessment by providers, beyond broad QOL assessments, and that attention to Sexual/Relationship Satisfaction may be critical in the development and implementation of interventions for this cohort of patients. © 2013 International Society for Sexual Medicine.

Defibrotide sodium for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome.

PubMed

Richardson, Paul G; Triplett, Brandon M; Ho, Vincent T; Chao, Nelson; Dignan, Fiona L; Maglio, Michelle; Mohty, Mohamad

2018-02-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is an unpredictable condition associated with endothelial-cell damage due to conditioning for hematopoietic stem-cell transplantation (HSCT) or chemotherapy without HSCT. Mortality in patients with VOD/SOS and multi-organ dysfunction (MOD) may be >80%. Areas covered: Defibrotide is the only approved drug for the treatment of severe hepatic VOD/SOS after HSCT in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction in the United States. Its efficacy in patients with VOD/SOS with MOD post-HSCT was demonstrated in a clinical-trial program that included a historically controlled treatment study, a phase 2 trial, and a large T-IND expanded-access program that also included patients without MOD and who received chemotherapy without HSCT. Expert commentary: Defibrotide appears to protect endothelial cells and restore the thrombolytic-fibrinolytic balance. It addresses a significant clinical need and has demonstrated favorable Day +100 survival and overall adverse-event rates that seem similar to control groups receiving supportive care alone. Currently, defibrotide is under investigation for the prevention of VOD/SOS in high-risk pediatric and adult patients.

Prevalence of multiple organ dysfunction in the pediatric intensive care unit: Pediatric Risk of Mortality III versus Pediatric Logistic Organ Dysfunction scores for mortality prediction

PubMed Central

Hamshary, Azza Abd Elkader El; Sherbini, Seham Awad El; Elgebaly, HebatAllah Fadel; Amin, Samah Abdelkrim

2017-01-01

Objectives To assess the frequency of primary multiple organ failure and the role of sepsis as a causative agent in critically ill pediatric patients; and calculate and evaluate the accuracy of the Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD) scores to predict the outcomes of critically ill children. Methods Retrospective study, which evaluated data from patients admitted from January to December 2011 in the pediatric intensive care unit of the Children's Hospital of the University of Cairo. Results Out of 237 patients in the study, 72% had multiple organ dysfunctions, and 45% had sepsis with multiple organ dysfunctions. The mortality rate in patients with multiple organ dysfunction was 73%. Independent risk factors for death were mechanical ventilation and neurological failure [OR: 36 and 3.3, respectively]. The PRISM III score was more accurate than the PELOD score in predicting death, with a Hosmer-Lemeshow X2 (Chi-square value) of 7.3 (df = 8, p = 0.5). The area under the curve was 0.723 for PRISM III and 0.78 for PELOD. Conclusion A multiple organ dysfunctions was associated with high mortality. Sepsis was the major cause. Pneumonia, diarrhea and central nervous system infections were the major causes of sepsis. PRISM III had a better calibration than the PELOD for prognosis of the patients, despite the high frequency of the multiple organ dysfunction syndrome. PMID:28977260

Impact on the Quality of Erections after Completing a Low-Intensity Extracorporeal Shock Wave Treatment Cycle on a Group of 710 Patients.

PubMed

Ayala, Héctor A Corredor; Cuartas, José Pablo Saffon; Cleves, Diana Cerquera

2017-01-01

The aim of this study is to evaluate the response to low-intensity extracorporeal shock wave therapy in a group of patients with organic vascular erectile dysfunction. This is an observational retrospective study. The researchers reviewed 710 patients with a clinical diagnosis of organic vascular erectile dysfunction (ED) of more than 3-month duration from male sexual health clinics of the Boston Medical Group from 12 cities in Spain and 4 in Mexico. Patients received 5 outpatient shock wave therapy sessions. They were evaluated with the erection hardness score (EHS) before the first session ( n  = 710), at the end of the last session ( n  = 710), and one month after the last session ( n  = 412). In the first examination, the EHS improved in 43.1% (306/710) of subjects compared to the baseline measurement and ability to penetrate increased from 26.8% to 44% ( p < 0.0001). In the second examination, the ability to penetrate was 37.9%, lower than in the first ( p =0.042) but higher than the baseline ( p =0.0001). The results suggest that the shock wave therapy with or without concomitant treatments improved the quality of erections in patients with erectile dysfunction treated in specialised male sexual health clinics. This trial is registered with NCT03237143.

The impact of duration of organ dysfunction on the outcome of patients with severe sepsis and septic shock.

PubMed

Freitas, Flávio G R; Salomão, Reinaldo; Tereran, Nathalia; Mazza, Bruno Franco; Assunção, Murillo; Jackiu, Mirian; Fernandes, Haggeas; Machado, Flávia Ribeiro

2008-08-01

This study aimed to assess the impact of the duration of organ dysfunction on the outcome of patients with severe sepsis or septic shock. Clinical data were collected from hospital charts of patients with severe sepsis and septic shock admitted to a mixed intensive care unit from November 2003 to February 2004. The duration of organ dysfunction prior to diagnosis was correlated with mortality. Results were considered significant if p<0.05. Fifty-six patients were enrolled. Mean age was 55.6+/-20.7 years, mean APACHE II score was 20.6+/-6.9, and mean SOFA score was 7.9+/-3.7. Thirty-six patients (64.3%) had septic shock. The mean duration of organ dysfunction was 1.9+/-1.9 days. Within the univariate analysis, the variables correlated with hospital mortality were: age (p=0.015), APACHE II (p=0.008), onset outside the intensive care unit (p=0.05), blood glucose control (p=0.05) and duration of organ dysfunction (p=0.0004). In the multivariate analysis, only a duration of organ dysfunction persisting longer than 48 hours correlated with mortality (p=0.004, OR: 8.73 (2.37-32.14)), whereas the APACHE II score remained only a slightly significant factor (p=0.049, OR: 1.11 (1.00-1.23)). Patients who received therapeutic interventions within the first 48 hours after the onset of organ dysfunction exhibited lower mortality (32.1% vs. 82.1%, p=0.0001). These findings suggest that the diagnosis of organ dysfunction is not being made in a timely manner. The time elapsed between the onset of organ dysfunction and initiation of therapeutic intervention can be quite long, and this represents an important determinant of survival in cases of severe sepsis and septic shock.

Sildenafil citrate for the management of antidepressant-associated erectile dysfunction.

PubMed

Nurnberg, H George; Hensley, Paula L

2003-01-01

Sexual side effects of serotonin reuptake inhibitors, such as antidepressant-associated erectile dysfunction, are common and negatively impact treatment compliance. Current management approaches have important limitations, and most lack clear and meaningful efficacy in double-blind, placebo-controlled trials. A MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sildenafil. Emphasis was placed on studies that used specific sexual function measurements and were placebo controlled. Sildenafil citrate, a selective and competitive inhibitor of phosphodiesterase type 5, enhances the cyclic guanosine monophosphate-mediated relaxation of cavernosal smooth muscles in response to sexual stimulation, permitting vascular engorgement and penile erection. The efficacy and tolerability of sildenafil in the treatment of antidepressant-associated erectile dysfunction have been confirmed in double-blind, placebo-controlled trials.

Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials.

PubMed

Danchin, Nicolas; Cucherat, Michel; Thuillez, Christian; Durand, Eric; Kadri, Zena; Steg, Philippe G

2006-04-10

Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction. We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced. Angiotensin-converting enzyme inhibitors reduce total mortality and major cardiovascular end points in patients who have CAD and no left ventricular systolic dysfunction or heart failure.

Clinical and billing review of extracorporeal membrane oxygenation.

PubMed

Blum, James M; Lynch, William R; Coopersmith, Craig M

2015-06-01

Extracorporeal membrane oxygenation (ECMO) is a temporary technique for providing life support for cardiac dysfunction, pulmonary dysfunction, or both. The two forms of ECMO, veno-arterial (VA) and veno-venous (VV), are used to support cardiopulmonary and pulmonary dysfunction, respectively. Historically, ECMO was predominantly used in the neonatal and pediatric populations, as early adult studies failed to improve outcomes. ECMO has become far more common in the adult population because of positive results in published case series and clinical trials during the 2009 influenza A(H1N1) pandemic in 2009 to 2010. Advances in technology that make the technique much easier to implement likely fueled the renewed interest. Although exact criteria for ECMO are not available, patients who are good candidates are generally considered to be relatively young and suffering from acute illness that is believed to be reversible or organ dysfunction that is otherwise treatable. With the increase in the use in the adult population, a number of different codes have been generated to better identify the method of support with distinctly different relative value units assigned to each code from a very simple prior coding scheme. To effectively be reimbursed for use of the technique, it is imperative that the clinician understands the new coding scheme and works with payers to determine what is incorporated into each specific code.

Non-operative management of posterior tibialis tendon dysfunction: design of a randomized clinical trial [NCT00279630

PubMed Central

Kulig, Kornelia; Pomrantz, Amy B; Burnfield, Judith M; Reischl, Stephen F; Mais-Requejo, Susan; Thordarson, David B; Smith, Ronald W

2006-01-01

Background Posterior tibialis tendon dysfunction (PTTD) is a common cause of foot pain and dysfunction in adults. Clinical observations strongly suggest that the condition is progressive. There are currently no controlled studies evaluating the effectiveness of exercise, orthoses, or orthoses and exercise on Stage I or IIA PTTD. Our study will explore the effectiveness of an eccentric versus concentric strengthening intervention to results obtained with the use of orthoses alone. Findings from this study will guide the development of more efficacious PTTD intervention programs and contribute to enhanced function and quality of life in persons with posterior tibialis tendon dysfunction. Methods/design This paper presents the rationale and design for a randomized clinical trial evaluating the effectiveness of a treatment regime for the non-operative management of Stage I or IIA PTTD. Discussion We have presented the rationale and design for an RCT evaluating the effectiveness of a treatment regimen for the non-operative management of Stage I or IIA PTTD. The results of this trial will be presented as soon as they are available. PMID:16756656

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

PubMed Central

Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier

2014-01-01

Sepsis — severe life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease. PMID:24232462

Deciphering the complexity of acute inflammation using mathematical models.

PubMed

Vodovotz, Yoram

2006-01-01

Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.

[New Concept for Surviving Sepsis: from Phenomenon to Essence].

PubMed

Liao, Xue-Lian; Xie, Zhi-Chao; Kang, Yan

2016-07-01

Sepsis is a critical clinical syndrome which keep puzzling the medical profession for many years. Recently, the results from several large-scale trials challenged the necessity of early goal directed therapy (EGDT) in surviving sepsis bundle, These trials were not opposed to EGDT but bring new concept that it is essential to utilize therapy with multiple monitoring measures in order to minimize injury while guarantee the safety . Deeper understanding in the pathogenesis of sepsis gives rise to the update of its definition based on vital organ dysfunction. The importance of dynamic monitoring in defining sepsis also need to be emphasized. Developing more effective monitoring measures could provide better treatments, thus improve the prognosis of septic patients. Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).

The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die.

PubMed

Weiss, Scott L; Balamuth, Fran; Hensley, Josey; Fitzgerald, Julie C; Bush, Jenny; Nadkarni, Vinay M; Thomas, Neal J; Hall, Mark; Muszynski, Jennifer

2017-09-01

The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era. Retrospective observational study. Emergency departments and ICUs at two academic children's hospitals. Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012-2013 who died prior to hospital discharge. None. Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1-12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction. Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies were limited. A pattern of persistent, rather than worsening, organ dysfunction preceded most deaths.

Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage

PubMed Central

2014-01-01

This article reviews current knowledge of the mechanisms underlying the initial hemorrhage and secondary blood–brain barrier (BBB) dysfunction in primary spontaneous intracerebral hemorrhage (ICH) in adults. Multiple etiologies are associated with ICH, for example, hypertension, Alzheimer’s disease, vascular malformations and coagulopathies (genetic or drug-induced). After the initial bleed, there can be continued bleeding over the first 24 hours, so-called hematoma expansion, which is associated with adverse outcomes. A number of clinical trials are focused on trying to limit such expansion. Significant progress has been made on the causes of BBB dysfunction after ICH at the molecular and cell signaling level. Blood components (e.g. thrombin, hemoglobin, iron) and the inflammatory response to those components play a large role in ICH-induced BBB dysfunction. There are current clinical trials of minimally invasive hematoma removal and iron chelation which may limit such dysfunction. Understanding the mechanisms underlying the initial hemorrhage and secondary BBB dysfunction in ICH is vital for developing methods to prevent and treat this devastating form of stroke. PMID:25120903

Bladder, bowel, and sexual dysfunction in Parkinson's disease.

PubMed

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called "pelvic organ" dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and "prokinetic" drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

Botulinum toxin for upper oesophageal sphincter dysfunction in neurological swallowing disorders.

PubMed

Regan, Julie; Murphy, Anne; Chiang, Mindy; McMahon, Barry P; Coughlan, Tara; Walshe, Margaret

2014-05-06

Adequate upper oesophageal sphincter (UOS) opening is critical to safe and efficient swallowing due to the close proximity of the UOS to the airway entrance. Many people with neurological conditions, progressive and non-progressive, present with UOS dysfunction. The consequences for the person include difficulty swallowing food with subsequent choking and aspiration (passage of material into the trachea beyond the level of the true vocal cords). Clinical complications include aspiration pneumonia, weight loss, dehydration and malnutrition. Tube feeding is often indicated but is associated with increased mortality. Quality of life is also frequently impacted. A range of interventions exist that aim to improve UOS function and swallowing. These include compensatory strategies, rehabilitation techniques, pharmacological interventions and surgery. Over the last two decades, botulinum toxin has been gaining popularity as an intervention for UOS dysfunction, with some evidence to suggest that it is successful in improving swallow function. Despite a number of studies investigating its efficacy, there is a lack of consensus regarding whether this intervention is effective in improving swallowing for individuals with UOS dysfunction associated with neurological disease. To establish the efficacy and safety of botulinum toxin use aimed at improving UOS dysfunction in people with swallowing difficulties (dysphagia) associated with non-progressive and progressive neurological disease. We searched the following electronic databases for published trials: the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (1950 to 2013); EMBASE (1980 to 2013); AMED (Allied and Complementary Medicine) (1941 to 2013); CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1937 to 2013). We also searched major clinical trials registers: CCT (http://www.controlled-trials.com); Clinical Trials (http://www.clinicaltrials.gov); Chinese Clinical Trial Register (www.chictr.org); ACTR (http://www.actr.org.au/. We examined the reference lists of all potentially relevant studies to identify further relevant trials. We handsearched published abstracts of conference proceedings from both the Dysphagia Research Society and the European Society of Swallowing Disorders. Digestive Disease Week (published in Gastroenterology) was also handsearched. Additionally, we searched ProQuest Dissertations & Theses for dissertation abstracts. Only randomised controlled trials were sought. Independent searches were completed by JR, AM, MC and MW. Two review authors (JR and MW) independently inspected titles, abstracts and key words identified from the literature search. No randomised controlled studies were retrieved. Twenty-nine studies were excluded, mainly on the basis of trial design. It was not possible to reach a conclusion on the efficacy and safety of botulinum toxin as an intervention for people with UOS dysfunction and neurological disease. There is insufficient evidence to inform clinical practice. Directions for future research are provided.

Improving sexual health in men with prostate cancer: randomised controlled trial of exercise and psychosexual therapies

PubMed Central

2014-01-01

Background Despite being a critical survivorship care issue, there is a clear gap in current knowledge of the optimal treatment of sexual dysfunction in men with prostate cancer. There is sound theoretical rationale and emerging evidence that exercise may be an innovative therapy to counteract sexual dysfunction in men with prostate cancer. Furthermore, despite the multidimensional aetiology of sexual dysfunction, there is a paucity of research investigating the efficacy of integrated treatment models. Therefore, the purpose of this study is to: 1) examine the efficacy of exercise as a therapy to aid in the management of sexual dysfunction in men with prostate cancer; 2) determine if combining exercise and brief psychosexual intervention results in more pronounced improvements in sexual health; and 3) assess if any benefit of exercise and psychosexual intervention on sexual dysfunction is sustained long term. Methods/Design A three-arm, multi-site randomised controlled trial involving 240 prostate cancer survivors will be implemented. Participants will be randomised to: 1) ‘Exercise’ intervention; 2) ‘Exercise + Psychosexual’ intervention; or 3) ‘Usual Care’. The Exercise group will receive a 6-month, group based, supervised resistance and aerobic exercise intervention. The Exercise + Psychosexual group will receive the same exercise intervention plus a brief psychosexual self-management intervention that addresses psychological and sexual well-being. The Usual Care group will maintain standard care for 6 months. Measurements for primary and secondary endpoints will take place at baseline, 6 months (post-intervention) and 1 year follow-up. The primary endpoint is sexual health and secondary endpoints include key factors associated with sexual health in men with prostate cancer. Discussion Sexual dysfunction is one of the most prevalent and distressing consequences of prostate cancer. Despite this, very little is known about the management of sexual dysfunction and current health care services do not adequately meet sexual health needs of survivors. This project will examine the potential role of exercise in the management of sexual dysfunction and evaluate a potential best-practice management approach by integrating pharmacological, physiological and psychological treatment modalities to address the complex and multifaceted aetiology of sexual dysfunction following cancer. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613001179729. PMID:24641777

Taxonomy of segmental myocardial systolic dysfunction

PubMed Central

McDiarmid, Adam K.; Pellicori, Pierpaolo; Cleland, John G.; Plein, Sven

2017-01-01

The terms used to describe different states of myocardial health and disease are poorly defined. Imprecision and inconsistency in nomenclature can lead to difficulty in interpreting and applying trial outcomes to clinical practice. In particular, the terms ‘viable’ and ‘hibernating’ are commonly applied interchangeably and incorrectly to myocardium that exhibits chronic contractile dysfunction in patients with ischaemic heart disease. The range of inherent differences amongst imaging modalities used to define myocardial health and disease add further challenges to consistent definitions. The results of several large trials have led to renewed discussion about the classification of dysfunctional myocardial segments. This article aims to describe the diverse myocardial pathologies that may affect the myocardium in ischaemic heart disease and cardiomyopathy, and how they may be assessed with non-invasive imaging techniques in order to provide a taxonomy of myocardial dysfunction. PMID:27147609

Urgent Chemotherapy in Sepsis-Like Shock Related to Hematologic Malignancies.

PubMed

Cherruault, Marlène; Le Goff, Marielle; Tamburini, Jérôme; Pène, Frédéric

2018-05-01

Hematologic malignancies may result in multiple organ involvement including pulmonary and renal dysfunctions, and the less common acute circulatory failure. We herein addressed the outcome of patients with sepsis-like shock related to aggressive hematologic malignancies. A 10-year (2007-2016) monocenter retrospective study. A medical ICU in a tertiary care center. Patients with circulatory shock requiring vasopressors and who subsequently received chemotherapy. Shock was presumably related to the underlying malignancy after ruling out an ongoing or new-onset infectious process. The extent and time course of organ failures was assessed by a modified Sequential Organ Failure Assessment score devoid of the platelet component. None. Seventeen patients were included, including 13 with non-Hodgkin lymphoma, two with hyperleukocytic acute myeloid leukemia, and two with "Human Herpes virus 8"-associated multicentric Castleman's disease. The following associated conditions prompted urgent administration of chemotherapy: tumor lysis syndrome (n = 10), hemophagocytic lymphohistiocytosis (n = 3), compressive bulky tumor (n = 3), pulmonary involvement (n = 3), and disseminated intravascular coagulation (n = 1). Following the initiation of chemotherapy, a number of patients died rapidly from untractable multiple organ failure. In contrast, chemotherapy led to a fast and dramatic improvement in organ failures in early survivors, as shown by the decrease in the modified Sequential Organ Failure Assessment score. However, the overall outcome was poor since only four and three patients could be discharged alive from the ICU and the hospital, and three and two patients remained alive at 6 months and 1 year. Multiple organ dysfunction syndrome related to hematologic malignancies is associated with a dismal outcome. A chemotherapy trial may provide a fast prognostic assessment of the reversibility of organ failure.

Cognitive computer training in children with attention deficit hyperactivity disorder (ADHD) versus no intervention: study protocol for a randomized controlled trial.

PubMed

Bikic, Aida; Leckman, James F; Lindschou, Jane; Christensen, Torben Ø; Dalsgaard, Søren

2015-10-24

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by symptoms of inattention and impulsivity and/or hyperactivity and a range of cognitive dysfunctions. Pharmacological treatment may be beneficial; however, many affected individuals continue to have difficulties with cognitive functions despite medical treatment, and up to 30 % do not respond to pharmacological treatment. Inadequate medical compliance and the long-term effects of treatment make it necessary to explore nonpharmacological and supplementary treatments for ADHD. Treatment of cognitive dysfunctions may prove particularly important because of the impact of these dysfunctions on the ability to cope with everyday life. Lately, several trials have shown promising results for cognitive computer training, often referred to as cognitive training, which focuses on particular parts of cognition, mostly on the working memory or attention but with poor generalization of training on other cognitive functions and functional outcome. Children with ADHD have a variety of cognitive dysfunctions, and it is important that cognitive training target multiple cognitive functions. This multicenter randomized clinical superiority trial aims to investigate the effect of "ACTIVATE™," a computer program designed to improve a range of cognitive skills and ADHD symptoms. A total of 122 children with ADHD, aged 6 to 13 years, will be randomized to an intervention or a control group. The intervention group will be asked to use ACTIVATE™ at home 40 minutes per day, 6 days per week for 8 weeks. Both intervention and control group will receive treatment as usual. Outcome measures will assess cognitive functions, symptoms, and behavioral and functional measures before and after the 8 weeks of training and in a 12- and 24-week follow-up. Results of this trial will provide useful information on the effectiveness of computer training focusing on several cognitive functions. Cognitive training has the potential to reduce cognitive dysfunctions and to become a new treatment option, which can promote a more normal neural development in young children with ADHD and thus reduce cognitive dysfunctions and symptoms. This could help children with ADHD to perform better in everyday life and school. ClinicalTrials.gov: NCT01752530 , date of registration: 10 December 2012.

Validating the WHO Maternal Near Miss Tool in a high-income country.

PubMed

Witteveen, Tom; de Koning, Ilona; Bezstarosti, Hans; van den Akker, Thomas; van Roosmalen, Jos; Bloemenkamp, Kitty W

2016-01-01

This study was performed to assess the applicability of the WHO Maternal Near Miss Tool (MNM Tool) and the organ dysfunction criteria in a high-income country. The MNM tool was applied to 2552 women who died of pregnancy-related causes or sustained severe acute maternal morbidity between August 2004 and August 2006 in one of the 98 hospitals with a maternity unit in the Netherlands. Fourteen (0.6%) cases had insufficient data for application. Each case was assessed according to the three main "MNM categories" specified in the MNM tool and their subcategory criteria: five disease-, four intervention- and seven organ dysfunction-based criteria. Potentially life-threatening conditions (disease-based inclusions) and life-threatening cases (organ dysfunction-based inclusions) were differentiated according to WHO methodology. Outcomes were incidence of all (sub)categories and case-fatality rates. Of the 2538 cases, 2308 (90.9%) women fulfilled disease-based, 2116 (83.4%) intervention-based and 1024 (40.3%) organ dysfunction-based criteria. Maternal death occurred in 48 women, of whom 23 (47.9%) fulfilled disease-based, 33 (68.8%) intervention-based and 31 (64.6%) organ dysfunction-based criteria. Case-fatality rates were 23/2308 (1.0%) for cases fulfilling the disease-based criteria, 33/2116 (1.6%) for intervention-based criteria and 31/1024 (3.0%) for women fulfilling the organ dysfunction-based criteria. In the Netherlands, where advanced laboratory and clinical monitoring are available, organ dysfunction-based criteria of the MNM tool failed to identify nearly two-thirds of sustained severe acute maternal morbidity cases and more than one-third of maternal deaths. Disease-based criteria remain important, and using only organ dysfunction-based criteria would lead to underestimating severe acute maternal morbidity. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT Study

PubMed Central

2011-01-01

Introduction Enteral nutrition (EN) with eicosapentaenoic acid (EPA)/γ-linolenic acid (GLA) is recommended for mechanically ventilated patients with severe lung injury. EPA/GLA has anti-inflammatory benefits, as evidenced by its association with reduction in pulmonary inflammation, improvement in oxygenation and improved clinical outcomes in patients with severe forms of acute lung injury. This study was a prospective, multicenter, randomized, double-blinded, controlled trial designed to investigate whether EPA/GLA could have an effective role in the treatment of patients with early sepsis (systemic inflammatory response syndrome with confirmed or presumed infection and without any organ dysfunction) by reducing the progression of the disease to severe sepsis (sepsis associated with at least one organ failure) or septic shock (sepsis associated with hypotension despite adequate fluid resuscitation). Secondary outcomes included the development of individual organ failure, increased ICU and hospital length of stay, need for mechanical ventilation and 28-day all-cause mortality. Methods Randomization was concealed, and patients were allocated to receive, for seven days, either an EPA/GLA diet or an isocaloric, isonitrogenous control diet not enhanced with lipids. Patients were continuously tube-fed at a minimum of 75% of basal energy expenditure × 1.3. To evaluate the progression to severe sepsis and/or septic shock, daily screening for individual organ failure was performed. All clinical outcomes were recorded during a 28-day follow-up period. Results A total of 115 patients in the early stages of sepsis requiring EN were included, among whom 106 were considered evaluable. Intention-to-treat (ITT) analysis demonstrated that patients fed the EPA/GLA diet developed less severe sepsis and/or septic shock than patients fed the control diet (26.3% versus 50%, respectively; P = 0.0259), with similar results observed for the evaluable patients (26.4% versus 50.9% respectively; P = 0.0217). The ITT analysis demonstrated that patients in the study group developed cardiovascular failure (36.2% versus 21%, respectively; P = 0.0381) and respiratory failure (39.6% versus 24.6%, respectively; P = 0.0362) less often than the control group. Similarly, when considering only the evaluable patients, fewer patientsdeveloped cardiovascular failure (20.7% versus 37.7%, respectively; P = 0.03) and respiratory failure (26.4% versus 39.6%, respectively; P = 0.04). The percentage of patients fed the EPA/GLA diet requiring invasive mechanical ventilation was reduced compared with controls (ITT patients: 18.9% versus 33.9%, respectively; P = 0.394; evaluable patients: 17.5% versus 34.5%, respectively; P = 0.295). Patients nourished with the EPA/GLA diet remained in the ICU fewer days than the control population (ITT patients: 21.1 ICU-free days versus 14.7 ICU-free days, respectively; P < 0.0001; evaluable patients: 20.8 ICU-free days versus 14.3 ICU-free days, respectively; P < 0.0001) and fewer days at the hospital (ITT patients: 19.5 hospital-free days versus 10.3 hospital-free days, respectively; P < 0.0001; evaluable patients: 19.1 hospital-free days versus 10.2 hospital-free days, respectively; P < 0.001) (all numbers expressed as means). No significant differences in 28-day all-cause mortality were observed (ITT patients: 26.2% EPA/GLA diet versus 27.6% control diet, respectively; P = 0.72; evaluable: 26.4 EPA/GLA diet versus 30.18 control diet, respectively; P = 0.79). Conclusions These data suggest that EPA/GLA may play a beneficial role in the treatment of enterally fed patients in the early stages of sepsis without associated organ dysfunction by contributing to slowing the progression of sepsis-related organ dysfunction, especially with regard to cardiovascular and respiratory dysfunction. Trial Registration ClinicalTrials.gov: NCT00981877 PMID:21658240

Taxonomy of segmental myocardial systolic dysfunction.

PubMed

McDiarmid, Adam K; Pellicori, Pierpaolo; Cleland, John G; Plein, Sven

2017-04-01

The terms used to describe different states of myocardial health and disease are poorly defined. Imprecision and inconsistency in nomenclature can lead to difficulty in interpreting and applying trial outcomes to clinical practice. In particular, the terms 'viable' and 'hibernating' are commonly applied interchangeably and incorrectly to myocardium that exhibits chronic contractile dysfunction in patients with ischaemic heart disease. The range of inherent differences amongst imaging modalities used to define myocardial health and disease add further challenges to consistent definitions. The results of several large trials have led to renewed discussion about the classification of dysfunctional myocardial segments. This article aims to describe the diverse myocardial pathologies that may affect the myocardium in ischaemic heart disease and cardiomyopathy, and how they may be assessed with non-invasive imaging techniques in order to provide a taxonomy of myocardial dysfunction. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Somatic dysfunction and its association with chronic low back pain, back-specific functioning, and general health: results from the OSTEOPATHIC Trial.

PubMed

Licciardone, John C; Kearns, Cathleen M

2012-07-01

Somatic dysfunction is diagnosed by the presence of any of 4 TART criteria: tissue texture abnormality, asymmetry, restriction of motion, or tenderness. To measure the prevalence of somatic dysfunction in patients with chronic low back pain (LBP) and to study the associations of somatic dysfunction with LBP severity, back-specific functioning, and general health. Cross-sectional study nested within a randomized controlled trial. University-based study in Dallas-Fort Worth, Texas. A total of 455 adult research patients with non-specific chronic LBP. Somatic dysfunction in the lumbar, sacrum/pelvis, and pelvis/innominate regions, including key lesions representing severe somatic dysfunction. A 10-cm visual analog scale (VAS), the Roland-Morris Disability Questionnaire (RMDQ), and the Medical Outcomes Study Short Form-36 Health Survey (SF-36) were used to measure LBP severity, back-specific functioning, and general health, respectively. Severe somatic dysfunction was most prevalent in the lumbar (225 [49%]), sacrum/pelvis (129 [28%]), and pelvis/innominate (48 [11%]) regions. Only 30 patients (7%) had no somatic dysfunction in the lumbar, sacrum/pelvis, or pelvis/innominate regions. There were 4 statistically significant pairwise correlations for severe somatic dysfunction: thoracic (T) 10-12 with ribs; T10-12 with lumbar; lumbar with sacrum/pelvis; and sacrum/pelvis with pelvis/innominate. Having a key lesion in the lumbar region (ρ=0.80) or sacrum/pelvis region (ρ=0.71) was strongly correlated with the overall number of key lesions. There were no consistent demographic or clinical predictors of somatic dysfunction. The presence (vs absence) of severe somatic dysfunction in the lumbar region was associated with greater LBP severity (median VAS score, 4.7 vs 3.8, respectively; P=.003) and greater back-specific disability (median RMDQ score, 6 vs 4, respectively; P=.01). The presence (vs absence) of severe somatic dysfunction in the sacrum/pelvis region was associated with greater back-specific disability (median RMDQ score, 6 vs 5, respectively; P=.02) and poorer general health (median SF-36 score, 62 vs 72, respectively; P=.002). An increasing number of key lesions was associated with back-specific disability (P=.009) and poorer general health (P=.02). The present study demonstrates that somatic dysfunction, particularly in the lumbar and sacrum/pelvis regions, is common in patients with chronic LBP. Forthcoming extensions of the OSTEOPATHIC Trial will assess the efficacy of OMT according to baseline levels of somatic dysfunction.

Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies.

PubMed

Pérez-Sánchez, Almudena; Barrajón-Catalán, Enrique; Herranz-López, María; Micol, Vicente

2018-03-24

The skin is the body's largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV) radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin.

Synergistic effect of acupuncture and mirror therapy on post-stroke upper limb dysfunction: a study protocol for a randomized controlled trial.

PubMed

Xu, Ying; Lin, Shufang; Jiang, Cai; Ye, Xiaoqian; Tao, Jing; Wilfried, Schupp; Wong, Alex W K; Chen, Lidian; Yang, Shanli

2018-05-31

Upper limb dysfunction is common after stroke, posing an important challenge for post-stroke rehabilitation. The clinical efficacy of acupuncture for the recovery of post-stroke upper limb function has been previously demonstrated. Mirror therapy (MT) has also been found to be effective. However, the effects of acupuncture and MT have not been systematically compared. This trial aims to elucidate the synergistic effects of acupuncture and MT on upper limb dysfunction after stroke. A 2 × 2 factorial randomized controlled trial will be conducted at the rehabilitation hospitals affiliated with Fujian University of Traditional Chinese Medicine. A total of 136 eligible subjects will be randomly divided into acupuncture treatment (AT), MT, combined treatment, and control groups in a 1:1:1:1 ratio. All subjects will receive conventional treatment. The interventions will be performed 5 days per week for 4 weeks. AT, MT, and combined treatment will be performed for 30 min per day (combined treatment: AT 15 min + MT 15 min). The primary outcomes in this study will be the mean change in scores on both the FMA and WMFT from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The secondary outcomes are the mean change in the scores on the Visual Analogue Scale, Stroke Impact Scale, and modified Barthel index. Medical abstraction of adverse events will be assessed at each visit. The results of this trial will demonstrate the synergistic effect of acupuncture and MT on upper limb motor dysfunction after stroke. In addition, whether AT and MT, either combined or alone, are more effective than the conventional treatment in the management of post-stroke upper limb dysfunction will also be determined. Chinese Clinical Trial Registry: ChiCTR-IOR-17011118 . Registered on April 11, 2017. Version number: 01.2016.09.1.

Randomized Trial of Clitoral Vacuum Suction Versus Vibratory Stimulation in Neurogenic Female Orgasmic Dysfunction.

PubMed

Alexander, Marcalee; Bashir, Khurram; Alexander, Craig; Marson, Lesley; Rosen, Raymond

2018-02-01

To examine the safety and efficacy of using a clitoral vacuum suction device (CVSD) versus vibratory stimulation (V) to treat orgasmic dysfunction in women with multiple sclerosis (MS) or spinal cord injury (SCI). Randomized clinical trial. Two academic medical centers. Women (N=31) including 20 with MS and 11 with SCI. A 12-week trial of the use of a CVSD versus V. Female Sexual Function Inventory (FSFI) and Female Sexual Distress Scale (FSDS). Twenty-three women (18 MS, 5 SCI) completed the study including 13 of 16 randomized to CVSD and 10 of 15 randomized to V. There was a statistically significant increase in total FSFI score (P=.011), desire (P=.009), arousal (P=.009), lubrication (P=.008), orgasm (P=.012), and satisfaction (P=.049), and a significant decrease in distress as measured by FSDS (P=.020) in subjects using the CVSD. In subjects who used V, there was a statistically significant increase in the orgasm subscale of the FSFI (P=.028). Subjects using the CVSD maintained improvements 4 weeks after treatment. CVSD is safe and overall efficacious to treat female neurogenic sexual dysfunction related to MS and SCI. V is also safe and efficacious for female neurogenic orgasmic dysfunction; however, results were limited to the active treatment period. Because of ease of access and cost, clinicians can consider use of V for women with MS or SCI with orgasmic dysfunction. CVSD is recommended for women with multiple sexual dysfunctions or for whom V is ineffective. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Sexual dysfunction in subjects treated with inhibitors of 5α-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysis.

PubMed

Corona, G; Tirabassi, G; Santi, D; Maseroli, E; Gacci, M; Dicuio, M; Sforza, A; Mannucci, E; Maggi, M

2017-07-01

Despite their efficacy in the treatment of benign prostatic hyperplasia, the popularity of inhibitors of 5α-reductase (5ARIs) is limited by their association with adverse sexual side effects. The aim of this study was to review and meta-analyze currently available randomized clinical trials evaluating the rate of sexual side effects in men treated with 5ARIs. An extensive Medline Embase and Cochrane search was performed including the following words: 'finasteride', 'dutasteride', 'benign prostatic hyperplasia'. Only placebo-controlled randomized clinical trials evaluating the effect of 5ARI in subjects with benign prostatic hyperplasia were considered. Of 383 retrieved articles, 17 were included in this study. Randomized clinical trials enrolled 24,463 in the active and 22,270 patients in the placebo arms, respectively, with a mean follow-up of 99 weeks and mean age of 64.0 years. No difference was observed between trials using finasteride or dutasteride as the active arm considering age, trial duration, prostate volume or International Prostatic Symptoms Score at enrollment. Overall, 5ARIs determined an increased risk of hypoactive sexual desire [OR = 1.54 (1.29; 1.82); p < 0.0001] and erectile dysfunction [OR = 1.47 (1.29; 1.68); p < 0.0001]. No difference between finasteride and dutasteride regarding the risk of hypoactive sexual desire and erectile dysfunction was observed. Meta-regression analysis showed that the risk of hypoactive sexual desire and erectile dysfunction was higher in subjects with lower Q max at enrollment and decreased as a function of trial follow-up. Conversely, no effect of age, low urinary tract symptom or prostate volume at enrollment as well as Q max at end-point was observed. In conclusion, present data show that the use of 5ARI significantly increases the risk of erectile dysfunction and hypoactive sexual desire in subjects with benign prostatic hyperplasia. Patients should be adequately informed before 5ARIs are prescribed. © 2017 American Society of Andrology and European Academy of Andrology.

Testing the Nanoparticle-Allostatic Cross Adaptation-Sensitization Model for Homeopathic Remedy Effects

PubMed Central

Bell, Iris R.; Koithan, Mary; Brooks, Audrey J.

2012-01-01

Key concepts of the Nanoparticle-Allostatic Cross-Adaptation-Sensitization (NPCAS) Model for the action of homeopathic remedies in living systems include source nanoparticles as low level environmental stressors, heterotypic hormesis, cross-adaptation, allostasis (stress response network), time-dependent sensitization with endogenous amplification and bidirectional change, and self-organizing complex adaptive systems. The model accommodates the requirement for measurable physical agents in the remedy (source nanoparticles and/or source adsorbed to silica nanoparticles). Hormetic adaptive responses in the organism, triggered by nanoparticles; bipolar, metaplastic change, dependent on the history of the organism. Clinical matching of the patient’s symptom picture, including modalities, to the symptom pattern that the source material can cause (cross-adaptation and cross-sensitization). Evidence for nanoparticle-related quantum macro-entanglement in homeopathic pathogenetic trials. This paper examines research implications of the model, discussing the following hypotheses: Variability in nanoparticle size, morphology, and aggregation affects remedy properties and reproducibility of findings. Homeopathic remedies modulate adaptive allostatic responses, with multiple dynamic short- and long-term effects. Simillimum remedy nanoparticles, as novel mild stressors corresponding to the organism’s dysfunction initiate time-dependent cross-sensitization, reversing the direction of dysfunctional reactivity to environmental stressors. The NPCAS model suggests a way forward for systematic research on homeopathy. The central proposition is that homeopathic treatment is a form of nanomedicine acting by modulation of endogenous adaptation and metaplastic amplification processes in the organism to enhance long-term systemic resilience and health. PMID:23290882

Mental health screening in women with severe pelvic organ prolapse, chronic fourth-degree obstetric tear and genital tract fistula in western Uganda.

PubMed

Krause, Hannah G; Hall, Barbara A; Ng, Shu-Kay; Natukunda, Harriet; Singasi, Isaac; Goh, Judith T W

2017-06-01

High levels of mental health dysfunction have been identified in women with genital tract fistula. The aim of this study was to use the General Health Questionnaire-28 (GHQ-28) to screen women in western Uganda with severe pelvic organ prolapse, chronic fourth-degree obstetric tear and genital tract fistula for risk of mental health dysfunction. Women undergoing surgery for severe pelvic organ prolapse, chronic fourth-degree obstetric tear, and genital tract fistula were interviewed using the GHQ-28 to screen for the risk of mental health dysfunction. A total of 125 women completed the GHQ-28, including 22 with pelvic organ prolapse, 47 with fourth-degree obstetric tear, 21 with genital tract fistula, and 35 controls. Nearly all women with these serious gynaecological conditions were positive for the risk of mental health dysfunction. In the domain assessing symptoms of severe depression, women with fourth-degree obstetric tear and genital tract fistula scored higher than women with pelvic organ prolapse. A significant risk of mental health dysfunction was identified in women with severe pelvic organ prolapse and chronic fourth-degree obstetric tear. These rates are similar to the high rates of mental health dysfunction in women with genital tract fistula. Identification and management of mental health dysfunction in women with these conditions should be a priority.

Amyloidosis: Pathogenesis and New Therapeutic Options

PubMed Central

Merlini, Giampaolo; Seldin, David C.; Gertz, Morie A.

2011-01-01

The systemic amyloidoses are a group of complex diseases caused by tissue deposition of misfolded proteins that results in progressive organ damage. The most common type, immunoglobulin light chain amyloidosis (AL), is caused by clonal plasma cells that produce misfolded light chains. The purpose of this review is to provide up-to-date information on diagnosis and treatment options for AL amyloidosis. Early, accurate diagnosis is the key to effective therapy, and unequivocal identification of the amyloidogenic protein may require advanced technologies and expertise. Prognosis is dominated by the extent of cardiac involvement, and cardiac staging directs the choice of therapy. Treatment for AL amyloidosis is highly individualized, determined on the basis of age, organ dysfunction, and regimen toxicities, and should be guided by biomarkers of hematologic and cardiac response. Alkylator-based chemotherapy is effective in almost two thirds of patients. Novel agents are also active, and trials are ongoing to establish their optimal use. Treatment algorithms will continue to be refined through controlled trials. Advances in basic research have led to the identification of new drug targets and therapeutic approaches, which will be integrated with chemotherapy in the future. PMID:21483018

Can the Pediatric Logistic Organ Dysfunction-2 Score on Day 1 Be Used in Clinical Criteria for Sepsis in Children?

PubMed

Leclerc, Francis; Duhamel, Alain; Deken, Valérie; Grandbastien, Bruno; Leteurtre, Stéphane

2017-08-01

A recent task force has proposed the use of Sequential Organ Failure Assessment in clinical criteria for sepsis in adults. We sought to evaluate the predictive validity for PICU mortality of the Pediatric Logistic Organ Dysfunction-2 and of the "quick" Pediatric Logistic Organ Dysfunction-2 scores on day 1 in children with suspected infection. Secondary analysis of the database used for the development and validation of the Pediatric Logistic Organ Dysfunction-2. Nine university-affiliated PICUs in Europe. Only children with hypotension-low systolic blood pressure or low mean blood pressure using age-adapted cutoffs-and lactatemia greater than 2 mmol/L were considered in shock. We developed the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 including tachycardia, hypotension, and altered mentation (Glasgow < 11): one point for each variable (range, 0-3). Outcome was mortality at PICU discharge. Discrimination (Area under receiver operating characteristic curve-95% CI) and calibration (goodness of fit test) of the scores were studied. This study included 862 children with suspected infection (median age: 12.3 mo; mortality: n = 60 [7.0%]). Area under the curve of the Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.91 (0.86-0.96) in children with suspected infection, 0.88 (0.79-0.96) in those with low systolic blood pressure and hyperlactatemia, and 0.91 (0.85-0.97) in those with low mean blood pressure and hyperlactatemia; calibration p value was 0.03, 0.36, and 0.49, respectively. A Pediatric Logistic Organ Dysfunction-2 score on day 1 greater than or equal to 8 reflected an overall risk of mortality greater than or equal to 9.3% in children with suspected infection. Area under the curve of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.82 (0.76-0.87) with systolic blood pressure or mean blood pressure; calibration p value was 0.89 and 0.72, respectively. A score greater than or equal to 2 reflected a mortality risk greater than or equal to 19.8% with systolic blood pressure and greater than or equal to 15.9% with mean blood pressure. Among children admitted to PICU with suspected infection, Pediatric Logistic Organ Dysfunction-2 score on day 1 was highly predictive of PICU mortality suggesting its use to standardize definitions and diagnostic criteria of pediatric sepsis. Further studies are needed to determine the usefulness of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 outside of the PICU.

Exposure therapy changes dysfunctional evaluations of somatic symptoms in patients with hypochondriasis (health anxiety). A randomized controlled trial.

PubMed

Weck, Florian; Neng, Julia M B; Schwind, Julia; Höfling, Volkmar

2015-08-01

Dysfunctional evaluations of somatic symptoms are considered a central factor in maintaining hypochondriasis. The aim of the current study was to investigate whether exposure therapy (ET) without cognitive restructuring is sufficient to change dysfunctional evaluations of somatic symptoms. The current study was based on a randomized controlled trial and compared patients with hypochondriasis (N=73) receiving ET or cognitive therapy (CT) to a wait list (WL) control group. In both the ET and CT groups, dysfunctional symptom evaluations changed significantly compared with the WL group. No differences between the ET and CT groups emerged. The relationship between the treatment condition (active treatment vs. WL) and reductions in health anxiety was mediated by changes in somatic symptom evaluations only in a specific card sorting procedure. We conclude that addressing dysfunctional symptom evaluations is a necessary precondition for the effective treatment of hypochondriasis. However, the results indicate that ET and CT appear to change those processes to a similar degree. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

PubMed Central

Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

2016-01-01

IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. CONCLUSIONS AND RELEVANCE These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis. PMID:26903338

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

PubMed

Singer, Mervyn; Deutschman, Clifford S; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig M; Hotchkiss, Richard S; Levy, Mitchell M; Marshall, John C; Martin, Greg S; Opal, Steven M; Rubenfeld, Gordon D; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C

2016-02-23

Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. To evaluate and, as needed, update definitions for sepsis and septic shock. A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design.

PubMed

Zangrillo, Alberto; Alvaro, Gabriele; Pisano, Antonio; Guarracino, Fabio; Lobreglio, Rosetta; Bradic, Nikola; Lembo, Rosalba; Gianni, Stefano; Calabrò, Maria Grazia; Likhvantsev, Valery; Grigoryev, Evgeny; Buscaglia, Giuseppe; Pala, Giovanni; Auci, Elisabetta; Amantea, Bruno; Monaco, Fabrizio; De Vuono, Giovanni; Corcione, Antonio; Galdieri, Nicola; Cariello, Claudia; Bove, Tiziana; Fominskiy, Evgeny; Auriemma, Stefano; Baiocchi, Massimo; Bianchi, Alessandro; Frontini, Mario; Paternoster, Gianluca; Sangalli, Fabio; Wang, Chew-Yin; Zucchetti, Maria Chiara; Biondi-Zoccai, Giuseppe; Gemma, Marco; Lipinski, Michael J; Lomivorotov, Vladimir V; Landoni, Giovanni

2016-07-01

Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Double-blind, placebo-controlled, multicenter randomized trial. Tertiary care hospitals. Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours. The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Vardenafil orodispersible tablet.

PubMed

Sanford, Mark

2012-01-01

Vardenafil orodispersible tablet (ODT) is a supralingual formulation of vardenafil that is available for the on-demand treatment of erectile dysfunction. The pharmacokinetics of vardenafil ODT are not equivalent to those of the vardenafil film-coated tablet in that the ODT formulation provides consistently greater vardenafil systemic exposure. Therefore, the two formulations are not interchangeable. The efficacy of on-demand vardenafil ODT 10 mg was established in the POTENT I and II studies, which were 6-week, randomized, double-blind, multinational trials in men with erectile dysfunction of at least 6 months duration. In both trials, vardenafil ODT improved erectile function significantly more than placebo, as indicated by International Index of Erectile Function-Erectile Function subscale scores at week 12 and overall erection success rates during treatment according to responses to questions 2 and 3 of the Sexual Encounter Profile (coprimary endpoints). In a pooled analysis of both trials, vardenafil ODT improved erectile function regardless of age, severity of erectile dysfunction at baseline or the presence or absence of underlying medical conditions. Vardenafil ODT was generally well tolerated in clinical trials, including in men aged ≥65 years, and adverse events were mostly mild or moderate in severity.

Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department

PubMed Central

Arnold, Ryan; Boyd, John H.; Zindovic, Marko; Zindovic, Igor; Lange, Anna; Paulsson, Magnus; Nyberg, Patrik; Russell, James A.; Pritchard, David; Christensson, Bertil; Åkesson, Per

2015-01-01

Objectives: Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. Design: A prospective international multicenter cohort study. Setting: Seven different emergency departments in Sweden, Canada, and the United States. Patients: Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). Intervention: None. Measurements and Main Results: Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12–24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (> 30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve = 0.80). The performance of heparin-binding protein was confirmed in the validation cohort. Conclusion: In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours. PMID:26468696

Early and simple detection of diastolic dysfunction during weaning from mechanical ventilation

PubMed Central

2012-01-01

Weaning from mechanical ventilation imposes additional work on the cardiovascular system and can provoke or unmask left ventricular diastolic dysfunction with consecutive pulmonary edema or systolic dysfunction with inadequate increase of cardiac output and unsuccessful weaning. Echocardiography, which is increasingly used for hemodynamic assessment of critically ill patients, allows differentiation between systolic and diastolic failure. For various reasons, transthoracic echocardiographic assessment was limited to patients with good echo visibility and to those with sinus rhythm without excessive tachycardia. In these patients, often selected after unsuccessful weaning, echocardiographic findings were predictive for weaning failure of cardiac origin. In some studies, patients with various degrees of systolic dysfunction were included, making evaluation of the diastolic dysfunction to the weaning failure even more difficult. The recent study by Moschietto and coworkers included unselected patients and used very simple diastolic variables for assessment of diastolic function. They also included patients with atrial fibrillation and repeated echocardiographic examination only 10 minutes after starting a spontaneous breathing trial. The main finding was that weaning failure was not associated with systolic dysfunction but with diastolic dysfunction. By measuring simple and robust parameters for detection of diastolic dysfunction, the study was able to predict weaning failure in patients with sinus rhythm and atrial fibrillation as early as 10 minutes after beginning a spontaneous breathing trial. Further studies are necessary to determine whether appropriate treatment tailored according to the echocardiographic findings will result in successful weaning. PMID:22770365

Early and simple detection of diastolic dysfunction during weaning from mechanical ventilation.

PubMed

Voga, Gorazd

2012-07-06

Weaning from mechanical ventilation imposes additional work on the cardiovascular system and can provoke or unmask left ventricular diastolic dysfunction with consecutive pulmonary edema or systolic dysfunction with inadequate increase of cardiac output and unsuccessful weaning. Echocardiography, which is increasingly used for hemodynamic assessment of critically ill patients, allows differentiation between systolic and diastolic failure. For various reasons, transthoracic echocardiographic assessment was limited to patients with good echo visibility and to those with sinus rhythm without excessive tachycardia. In these patients, often selected after unsuccessful weaning, echocardiographic findings were predictive for weaning failure of cardiac origin. In some studies, patients with various degrees of systolic dysfunction were included, making evaluation of the diastolic dysfunction to the weaning failure even more difficult. The recent study by Moschietto and coworkers included unselected patients and used very simple diastolic variables for assessment of diastolic function. They also included patients with atrial fibrillation and repeated echocardiographic examination only 10 minutes after starting a spontaneous breathing trial. The main finding was that weaning failure was not associated with systolic dysfunction but with diastolic dysfunction. By measuring simple and robust parameters for detection of diastolic dysfunction, the study was able to predict weaning failure in patients with sinus rhythm and atrial fibrillation as early as 10 minutes after beginning a spontaneous breathing trial. Further studies are necessary to determine whether appropriate treatment tailored according to the echocardiographic findings will result in successful weaning.

Should the patient with coronary artery disease use sildenafil?

PubMed

Cheitlin, Melvin D

2003-01-01

Since the etiology of erectile dysfunction is frequently related to endothelial dysfunction, a problem in common with much vascular disease, erectile dysfunction disproportionately affects patients with cardiovascular disease. With the development of phosphodiesterase 5 inhibitors, the first of which was sildenafil (Viagra), an effective oral medication became available. The question of safety of these drugs, especially in patients with latent or overt coronary artery disease, is of concern. Sildenafil relaxes smooth muscle and therefore lowers systolic and diastolic blood pressure slightly. With organic nitrates, the drop in blood pressure is potentiated, at times dangerously, thereby making it contraindicated to take nitrates within 24 hours of using sildenafil. In double-blind, placebo-controlled trials, there was no difference between sildenafil subjects and control patients in the incidence of myocardial infarction, cardiovascular, and total deaths. Coronary disease patients with stable angina, controlled on medications, were included in the trials. Therefore, sildenafil, as a drug, is safe in such patients. With a patient with coronary artery disease suddenly engaging in the physical exercise associated with sexual intercourse, there is the danger of increased risk of precipitating myocardial infarction or death. The cardiovascular metabolic cost of sexual activity is reviewed and appears to be approximately at the level of 3-5 metabolic equivalents of exercise. Sexual activity occurs within 2 hours of the onset of an acute myocardial infarction in <1.0% of patients. Although sexual intercourse is estimated to increase the risk of myocardial infarction by a factor of 2x, there is still only a very small increase in risk, a risk acceptable to patients who feel their quality of life will be markedly improved by their ability to engage in sexual activity.

Update on argatroban for the prophylaxis and treatment of heparin-induced thrombocytopenia type II

PubMed Central

Grouzi, Elisavet

2014-01-01

Heparin-induced thrombocytopenia (HIT) is a rare but potentially severe complication of heparin therapy that is strongly associated with venous and arterial thrombosis (HIT and thrombosis syndrome, HITTS), which requires urgent detection and treatment with a nonheparin anticoagulant. Argatroban, a synthetic direct thrombin inhibitor, is indicated for the treatment and prophylaxis of thrombosis in patients with HIT, including those undergoing percutaneous coronary intervention. Argatroban has a relatively short elimination half-life of approximately 45 minutes, which is predominantly performed via hepatic metabolism. It is derived from L-arginine that selectively and reversibly inhibits thrombin, both clot-bound and free, at the catalytic site. Argatroban anticoagulation has been systematically studied in patients with HIT and HITTS and proved to be a safe and effective agent for this indication. The current review presents the pharmacology of argatroban, data regarding monitoring of the agent, and an overview of the results of the major clinical trials assessing argatroban anticoagulation in HIT patients. Additionally, data from recent clinical trials with argatroban use in more special indications such as in percutaneous coronary intervention, liver dysfunction, renal replacement therapy, and intensive care medicine, are reviewed. The approved initial dosage of argatroban for adults with HIT or HITTS is 2 μg/kg/minute for patients with normal hepatic function and 0.5 μg/kg/minute for patients with hepatic dysfunction. There is evidence that a reduced initial dose may also be advisable for patients with heart failure, multiple organ dysfunction, severe anasarca, or after cardiac surgery. Given this information, argatroban can be effectively used in treating HIT with monitoring of activated partial thromboplastin time. PMID:25152637

Comparative effectiveness of 30 % trisodium citrate and heparin lock solution in preventing infection and dysfunction of hemodialysis catheters: a randomized controlled trial (CITRIM trial).

PubMed

Correa Barcellos, Franklin; Pereira Nunes, Bruno; Jorge Valle, Luciana; Lopes, Thiago; Orlando, Bianca; Scherer, Cintia; Nunes, Marcia; Araújo Duarte, Gabriela; Böhlke, Maristela

2017-04-01

Central venous catheters (CVC) are the only option when hemodialysis is needed for patients without definitive vascular access. However, CVC is associated with complications, such as infection, thrombosis, and dysfunction, leading to higher mortality and expenditures. The aim of this study was to compare the effectiveness of 30 % trisodium citrate (TSC30 %) with heparin as CVC lock solutions in preventing catheter-related bloodstream infections (CRBSI) and dysfunction in hemodialysis patients. Randomized, double-blind controlled trial comparing the event-free survival of non-tunneled CVC locked with heparin or TSC30 % in adult hemodialysis patients. The study included 464 catheters, 233 in heparin group, and 231 in TSC30 % group. The CRBSI-free survival of TSC30 % group was significantly shorter than that of heparin group. When stratified by insertion site, heparin was better than TSC30 % only in subclavian CVC. The dysfunction-free survival was not different between groups in the main analysis, but there is also a shorter survival among subclavian CVC locked with TSC30 % in stratified analysis. There was no difference on CRBSI-free or dysfunction-free survival between jugular vein CVC locked with heparin or 30 % citrate. However, subclavian CVC locked with 30 % citrate presented shorter event-free survival. This difference may be related to anatomical and positional effects, CVC design, and hydraulic aspects of the lock solution. CLINICALTRIALS. NCT02563041.

A Randomized Trial of the Effects of Nebulized Albuterol on Pulmonary Edema in Brain Dead Organ Donors

PubMed Central

Ware, Lorraine B.; Landeck, Megan; Koyama, Tatsuki; Zhao, Zhiguo; Singer, Jonathan; Kern, Ryan; Neidlinger, Nikole; Nguyen, John; Johnson, Elizabeth; Janz, David R.; Bernard, Gordon R.; Lee, Jae W.; Matthay, Michael A.

2013-01-01

Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5 mg q4h) versus saline placebo during active donor management in 506 organ donors. The primary outcome was change in oxygenation (PaO2/FiO2) from enrollment to organ procurement. The albuterol (n=260) and placebo (n=246) groups were well matched for age, gender, ethnicity, smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p=0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%, p=0.44). Donors in the albuterol vs. placebo group were more likely to have the study drug dose reduced (13% vs. 1%, p<0.001) or stopped (8% vs. 0%, p<0.001) for tachycardia. In summary, treatment with high dose inhaled albuterol during the donor management period did not improve donor oxygenation or increase donor lung utilization but did cause tachycardia. High dose aerosolized albuterol should not be used in donors to enhance the resolution of pulmonary edema. PMID:24730050

Oxidative Stress and Mitochondrial Dysfunction across Broad-Ranging Pathologies: Toward Mitochondria-Targeted Clinical Strategies

PubMed Central

d'Ischia, Marco; Gadaleta, Maria Nicola; Pallardó, Federico V.; Petrović, Sandra; Tiano, Luca; Zatterale, Adriana

2014-01-01

Beyond the disorders recognized as mitochondrial diseases, abnormalities in function and/or ultrastructure of mitochondria have been reported in several unrelated pathologies. These encompass ageing, malformations, and a number of genetic or acquired diseases, as diabetes and cardiologic, haematologic, organ-specific (e.g., eye or liver), neurologic and psychiatric, autoimmune, and dermatologic disorders. The mechanistic grounds for mitochondrial dysfunction (MDF) along with the occurrence of oxidative stress (OS) have been investigated within the pathogenesis of individual disorders or in groups of interrelated disorders. We attempt to review broad-ranging pathologies that involve mitochondrial-specific deficiencies or rely on cytosol-derived prooxidant states or on autoimmune-induced mitochondrial damage. The established knowledge in these subjects warrants studies aimed at elucidating several open questions that are highlighted in the present review. The relevance of OS and MDF in different pathologies may establish the grounds for chemoprevention trials aimed at compensating OS/MDF by means of antioxidants and mitochondrial nutrients. PMID:24876913

Tissue angiotensin-converting enzyme inhibitors for the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure: a pooled meta-analysis of randomized placebo-controlled clinical trials.

PubMed

Saha, S A; Molnar, J; Arora, R R

2008-01-01

The aim of this study was to determine the role of tissue angiotensin-converting enzyme (ACE) inhibitors in the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure in randomized placebo-controlled clinical trials using pooled meta-analysis techniques. Randomized placebo-controlled clinical trials of at least 12 months duration in patients with diabetes mellitus without left ventricular systolic dysfunction or heart failure who had experienced a prior cardiovascular event or were at high cardiovascular risk were selected. A total of 10 328 patients (43 517 patient-years) from four selected trials were used for meta-analysis. Relative risk estimations were made using data pooled from the selected trials and statistical significance was determined using the Chi-squared test (two-sided alpha error <0.05). The number of patients needed to treat was also calculated. Tissue ACE inhibitors significantly reduced the risk of cardiovascular mortality by 14.9% (p = 0.022), myocardial infarction by 20.8% (p = 0.002) and the need for invasive coronary revascularization by 14% (p = 0.015) when compared to placebo. The risk of all-cause mortality also tended to be lower among patients randomized to tissue ACE inhibitors, whereas the risks of stroke and hospitalization for heart failure were not significantly affected. Treating about 65 patients with tissue ACE inhibitors for about 4.2 years would prevent one myocardial infarction, whereas treating about 85 patients would prevent one cardiovascular death. Pooled meta-analysis of randomized placebo-controlled trials suggests that tissue ACE inhibitors modestly reduce the risk of myocardial infarction and cardiovascular death and tend to reduce overall mortality in diabetic patients without left ventricular systolic dysfunction or heart failure.

Cardio-renal syndromes: a systematic approach for consensus definition and classification.

PubMed

Ronco, Claudio; Ronco, Federico

2012-03-01

The "Cardio-Renal Syndrome" (CRS) is a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The general definition has been expanded to five subtypes reflecting the primacy of organ dysfunction and the time-frame of the syndrome: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Different pathophysiological mechanisms are involved in the combined dysfunction of heart and kidney in these five types of the syndrome.

Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia.

PubMed

Fitzhugh, Courtney D; Hsieh, Matthew M; Allen, Darlene; Coles, Wynona A; Seamon, Cassie; Ring, Michael; Zhao, Xiongce; Minniti, Caterina P; Rodgers, Griffin P; Schechter, Alan N; Tisdale, John F; Taylor, James G

2015-01-01

Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea. We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010. An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648. Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00-1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23-4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34-0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15-35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17-0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels. Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings.

Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia

PubMed Central

Fitzhugh, Courtney D.; Hsieh, Matthew M.; Allen, Darlene; Coles, Wynona A.; Seamon, Cassie; Ring, Michael; Zhao, Xiongce; Minniti, Caterina P.; Rodgers, Griffin P.; Schechter, Alan N.; Tisdale, John F.; Taylor, James G.

2015-01-01

Background Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea. Objectives We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010. Methods An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648. Results Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003–1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00–1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23–4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34–0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15–35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17–0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels. Conclusions Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings. PMID:26576059

New Diagnostic Terminology for Minimal Brain Dysfunction.

ERIC Educational Resources Information Center

Shaywitz, Bennett A.; And Others

1979-01-01

Minimal brain dysfunction has been redefined by the American Psychological Association as attention deficit disorder (ADD) and subdivided into categories with and without hyperactivity. The revised 'Diagnostic and Statistical Manual' (DSM III) is now undergoing field trials. Journal Availability: C. V. Mosby Company, 11830 Westline Industrial…

Positive inotropes in heart failure: a review article

PubMed Central

Amin, Ahmad; Maleki, Majid

2012-01-01

Increasing myocardial contractility has long been considered a big help for patients with systolic heart failure, conferring an augmented haemodynamic profile in terms of higher cardiac output, lower cardiac filling pressure and better organ perfusion. Though concerns have been raised over the safety issues regarding the clinical trials of different inotropes in hearts with systolic dysfunction, they still stand as a main therapeutic strategy in many centres dealing with such patients. They must be used as short in duration, low in dose and stopped as early as possible. Evidence-based guidelines have provided clinicians with valuable data for better applying inotropes in heart failure patients. In this paper, the authors address clinical trials with different agents used for increasing cardiac contractility in heart failure patients. Furthermore, the authors focus on recent guidelines on making the most out of inotropes in heart failure patients. PMID:27326019

Sexual dysfunctions in women.

PubMed

Meston, Cindy M; Bradford, Andrea

2007-01-01

In this article, we summarize the definition, etiology, assessment, and treatment of sexual dysfunctions in women. Although the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV-TR) is our guiding framework for classifying and defining women's sexual dysfunctions, we draw special attention to recent discussion in the literature criticizing the DSM-IV-TR diagnostic criteria and their underlying assumptions. Our review of clinical research on sexual dysfunction summarizes psychosocial and biomedical management approaches, with a critical examination of the empirical support for commonly prescribed therapies and limitations of recent clinical trials.

Comparison effect of physiotherapy with surgery on sexual function in patients with pelvic floor disorder: A randomized clinical trial.

PubMed

Eftekhar, Tahereh; Sohrabi, Maryam; Haghollahi, Fedyeh; Shariat, Mamak; Miri, Elahe

2014-01-01

Female sexual dysfunction is a common problem among general population, especially in urogynecological patient, and can lead to a decrease in quality of life and affect martial relationship. This study was compared the effect of surgical methods versus physiotherapy on sexual function in pelvic floor disorder. This randomized controlled trial was performed in Urogynecology clinic since August 2007 to December 2009 on 90 patients aged from 25-55 years with previous delivery, positive history of sexual dysfunction with stage <3 of pelvic organ prolapsed and divided in two groups. Group A (n=45) received standard rectocele repair and prineorrhaphy, group B (n=45) received physiotherapy for eight weeks twice a week (electrical stimulation, Kegel exercises). The female sexual function index (FSFI) used to evaluate the sexual function in cases before and after intervention. Frequency of variable scores (libido, orgasm, dysparunia) included without disorder, frequently good, sometimes good, very much and extreme were compared between two groups. Libido and arousal were improved in both groups (p=0.007, p=0.001 respectively). Orgasm and dyspareunia were improved in group B (p=0.001). Dysparunia was more painful in group A. There was significant difference between two groups (improvement of orgasm and dysparunia in group B) (p=0.001). It seems that physiotherapy is an appropriate method for treatment of sexual disorder in pelvic floor disorder. IRCT2013031112790N1.

Early organ-specific mitochondrial dysfunction of jejunum and lung found in rats with experimental acute pancreatitis

PubMed Central

Mittal, Anubhav; Hickey, Anthony JR; Chai, Chau C; Loveday, Benjamin PT; Thompson, Nichola; Dare, Anna; Delahunt, Brett; Cooper, Garth JS; Windsor, John A; Phillips, Anthony RJ

2011-01-01

Introduction Multiple organ dysfunction is the main cause of death in severe acute pancreatitis. Primary mitochondrial dysfunction plays a central role in the development and progression of organ failure in critical illness. The present study investigated mitochondrial function in seven tissues during early experimental acute pancreatitis. Methods Twenty-eight male Wistar rats (463 ± 2 g; mean ± SEM) were studied. Group 1 (n = 8), saline control; Group 2 (n = 6), caerulein-induced mild acute pancreatitis; Group 3 (n = 7) sham surgical controls; and Group 4 (n = 7), taurocholate-induced severe acute pancreatitis. Animals were euthanased at 6 h from the induction of acute pancreatitis and mitochondrial function was assessed in the heart, lung, liver, kidney, pancreas, duodenum and jejunum by mitochondrial respirometry. Results Significant early mitochondrial dysfunction was present in the pancreas, lung and jejunum in both models of acute pancreatitis, however, the Heart, liver, kidney and duodenal mitochondria were unaffected. Conclusions The present study provides the first description of early organ-selective mitochondrial dysfunction in the lung and jejunum during acute pancreatitis. Research is now needed to identify the underlying pathophysiology behind the organ selective mitochondrial dysfunction, and the potential benefits of early mitochondrial-specific therapies in acute pancreatitis. PMID:21492333

The synergistic effect of acupuncture and computer-based cognitive training on post-stroke cognitive dysfunction: a study protocol for a randomized controlled trial of 2 × 2 factorial design.

PubMed

Yang, Shanli; Ye, Haicheng; Huang, Jia; Tao, Jing; Jiang, Cai; Lin, Zhicheng; Zheng, Guohua; Chen, Lidian

2014-08-07

Stroke is one of the most common causes of cognitive impairment. Up to 75% of stroke survivors may be considered to have cognitive impairment, which severely limit individual autonomy for successful reintegration into family, work and social life. The clinical efficacy of acupuncture with Baihui (DU20) and Shenting (DU24) in stroke and post-stroke cognitive impairment has been previously demonstrated. Computer-assisted cognitive training is part of conventional cognitive rehabilitation and has also shown to be effective in improvement of cognitive function of affected patients. However, the cognitive impairment after stroke is so complexity that one single treatment cannot resolve effectively. Besides, the effects of acupuncture and RehaCom cognitive training have not been systematically compared, nor has the possibility of a synergistic effect of combination of the two therapeutic modalities been evaluated. Our primary aim of this trial is to evaluate the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. A randomized controlled trial of 2 × 2 factorial design will be conducted in the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine. A total of 240 patients with cognitive dysfunction after stroke who meet the eligibility criteria will be recruited and randomized into RehaCom training group, acupuncture group, a combination of both or control group in a 1:1:1:1 ratio. All patients will receive conventional treatment. The interventions will last for 12 weeks (30 min per day, Monday to Friday every week). Evaluations will be conducted by blinded assessors at baseline and again at 4, 8 and 12 weeks. Outcome measurements include mini-mental state examination (MMSE), Montreal cognitive assessments (MoCA), functional independence measure scale (FIM) and adverse events. The results of this trial are expected to clarify the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. Furthermore, to confirm whether combined or alone of acupuncture and RehaCom cognitive training, is more effective than conventional treatment in the management of post-stroke cognitive dysfunction. Chinese Clinical Trial Registry: ChiCTR-TRC-13003704.

Neutrophils in critical illness.

PubMed

McDonald, Braedon

2018-03-01

During critical illness, dramatic alterations in neutrophil biology are observed including abnormalities of granulopoeisis and lifespan, cell trafficking and antimicrobial effector functions. As a result, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. In this article, the role of neutrophils in the pathogenesis of critical illness (sepsis, trauma, burns and others) will be explored, including pathological changes to neutrophil function during critical illness and the utility of monitoring aspects of the neutrophil phenotype as biomarkers for diagnosis and prognostication. Lastly, we review findings from clinical trials of therapies that target the harmful effects of neutrophils, providing a bench-to-bedside perspective on neutrophils in critical illness.

Cardiovascular risk and sildenafil.

PubMed

Kloner, R A

2000-07-20

Sildenafil citrate is the first oral agent approved for the treatment of erectile dysfunction (ED); other oral agents are in the process of development. Because the mechanism of action of many of these agents involves vasodilation, there is a potential for interaction with the cardiovascular system. Sildenafil inhibits phosphodiesterase-5 (PDE-5) which is found in the corpus cavernosum and in the systemic vasculature. Sildenafil causes a mild decrease in systemic arterial pressure ( approximately -8/-5.5 mm Hg); it causes a synergistic and often major decrease in systemic arterial pressure in the presence of organic nitrates (nitric oxide donors). Sildenafil is therefore contraindicated in patients taking organic nitrates. A review was made of clinical trials in populations of men with (1) erectile dysfunction; (2) chronic stable ischemic heart disease and erectile dysfunction; and (3) hypertension and erectile dysfunction. This review showed that sildenafil was effective and not associated with an increase in serious cardiovascular adverse events, myocardial infarction (MI), or death compared with placebo. Although there have been spontaneous reports of death among men using sildenafil, there are limitations to spontaneous-event reporting. In addition. the numbers of such reports are well below the expected numbers of deaths when considering the number of men who have received prescriptions for sildenafil and their age and cardiovascular risk factor profile. Because there is a small but finite risk of having a cardiac event with sexual activity, physicians should discuss with their cardiac patients the risks of sexual activity before prescribing any treatment for ED. In addition, they should evaluate their patients' cardiac status when considering the safety of administering any ED treatment that may have systemic vasodilatory properties and can potentially lower blood pressure. In some cases, exercise treadmill testing may be warranted to determine whether ED patients with coronary artery disease can achieve the physiologic workload (4-6 metabolic equivalents) associated with sexual intercourse.

Risk of Erectile Dysfunction in Transfusion-naive Thalassemia Men

PubMed Central

Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

2015-01-01

Abstract Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities. PMID:25837766

Risk of erectile dysfunction in transfusion-naive thalassemia men: a nationwide population-based retrospective cohort study.

PubMed

Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

2015-04-01

Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction. This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities.

Alzheimer's disease, cerebrovascular dysfunction and the benefits of exercise: from vessels to neurons.

PubMed

Lange-Asschenfeldt, Christian; Kojda, Georg

2008-06-01

Exercise training promotes extensive cardiovascular changes and adaptive mechanisms in both the peripheral and cerebral vasculature, such as improved organ blood flow, induction of antioxidant pathways, and enhanced angiogenesis and vascular regeneration. Clinical studies have demonstrated a reduction of morbidity and mortality from cardiovascular disease among exercising individuals. However, evidence from recent large clinical trials also suggests a substantial reduction of dementia risk - particularly regarding Alzheimer's disease (AD) - with regular exercise. Enhanced neurogenesis and improved synaptic plasticity have been implicated in this beneficial effect. However, recent research has revealed that vascular and specifically endothelial dysfunction is essentially involved in the disease process and profoundly aggravates underlying neurodegeneration. Moreover, vascular risk factors (VRFs) are probably determinants of incidence and course of AD. In this review, we emphasize the interconnection between AD and VRFs and the impact of cerebrovascular and endothelial dysfunction on AD pathophysiology. Furthermore, we describe the molecular mechanisms of the beneficial effects of exercise on the vasculature such as activation of the vascular nitric oxide (NO)/endothelial NO synthase (eNOS) pathway, upregulation of antioxidant enzymes, and angiogenesis. Finally, recent prospective clinical studies dealing with the effect of exercise on the risk of incident AD are briefly reviewed. We conclude that, next to upholding neuronal plasticity, regular exercise may counteract AD pathophysiology by building a vascular reserve.

[Dysfunctional workplace organization and mobbing. 4 representative cases].

PubMed

Albini, Elisa; Benedetti, Laura; Giordano, S; Punzi, Silvia; Cassitto, Maria Grazia

2003-01-01

Stress and psychological harassment at work are increasing worldwide, according to International Agencies (European Community, NIOSH) and to most authors. To describe typical working situations responsible for distress and mobbing, with the aim of early diagnosis and effectiveness of therapy and rehabilitation. Four cases are reported as representative of dysfunctional organization producing distress and pathology or inducing mobbing behavior or mobbing without clear organization responsibilities. In all cases dysfunctional organization appeared to have played a significant role even though not always a direct one. Also, common characteristics were highlighted in the three cases where mobbing was recognized.

Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK-a randomized controlled trial.

PubMed

Hernández, Glenn; Cavalcanti, Alexandre Biasi; Ospina-Tascón, Gustavo; Zampieri, Fernando Godinho; Dubin, Arnaldo; Hurtado, F Javier; Friedman, Gilberto; Castro, Ricardo; Alegría, Leyla; Cecconi, Maurizio; Teboul, Jean-Louis; Bakker, Jan

2018-04-23

Septic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate-targeted resuscitation is the gold-standard under current guidelines, although it has several pitfalls including that non-hypoxic sources of lactate might predominate in an unknown proportion of patients. Peripheral perfusion-targeted resuscitation might provide a real-time response to increases in flow that could lead to a more timely decision to stop resuscitation, thus avoiding fluid overload and the risks of over-resuscitation. This article reports the rationale, study design and analysis plan of the ANDROMEDA-SHOCK Study. ANDROMEDA-SHOCK is a randomized controlled trial which aims to determine if a peripheral perfusion-targeted resuscitation is associated with lower 28-day mortality compared to a lactate-targeted resuscitation in patients with septic shock with less than 4 h of diagnosis. Both groups will be treated with the same sequential approach during the 8-hour study period pursuing normalization of capillary refill time versus normalization or a decrease of more than 20% of lactate every 2 h. The common protocol starts with fluid responsiveness assessment and fluid loading in responders, followed by a vasopressor and an inodilator test if necessary. The primary outcome is 28-day mortality, and the secondary outcomes are: free days of mechanical ventilation, renal replacement therapy and vasopressor support during the first 28 days after randomization; multiple organ dysfunction during the first 72 h after randomization; intensive care unit and hospital lengths of stay; and all-cause mortality at 90-day. A sample size of 422 patients was calculated to detect a 15% absolute reduction in mortality in the peripheral perfusion group with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. If peripheral perfusion-targeted resuscitation improves 28-day mortality, this could lead to simplified algorithms, assessing almost in real-time the reperfusion process, and pursuing more physiologically sound objectives. At the end, it might prevent the risk of over-resuscitation and lead to a better utilization of intensive care unit resources. Trial registration ClinicalTrials.gov Identifier: NCT03078712 (registered retrospectively March 13th, 2017).

Sleep-Related Safety Behaviors and Dysfunctional Beliefs Mediate the Efficacy of Online CBT for Insomnia: A Randomized Controlled Trial.

PubMed

Lancee, Jaap; Eisma, Maarten C; van Straten, Annemieke; Kamphuis, Jan H

2015-01-01

Several trials have demonstrated the efficacy of online cognitive behavioral therapy (CBT) for insomnia. However, few studies have examined putative mechanisms of change based on the cognitive model of insomnia. Identification of modifiable mechanisms by which the treatment works may guide efforts to further improve the efficacy of insomnia treatment. The current study therefore has two aims: (1) to replicate the finding that online CBT is effective for insomnia and (2) to test putative mechanism of change (i.e., safety behaviors and dysfunctional beliefs). Accordingly, we conducted a randomized controlled trial in which individuals with insomnia were randomized to either online CBT for insomnia (n = 36) or a waiting-list control group (n = 27). Baseline and posttest assessments included questionnaires assessing insomnia severity, safety behaviors, dysfunctional beliefs, anxiety and depression, and a sleep diary. Three- and six-month assessments were administered to the CBT group only. Results show moderate to large statistically significant effects of the online treatment compared to the waiting list on insomnia severity, sleep measures, sleep safety behaviors, and dysfunctional beliefs. Furthermore, dysfunctional beliefs and safety behaviors mediated the effects of treatment on insomnia severity and sleep efficiency. Together, these findings corroborate the efficacy of online CBT for insomnia, and suggest that these effects were produced by changing maladaptive beliefs, as well as safety behaviors. Treatment protocols for insomnia may specifically be enhanced by more focused attention on the comprehensive fading of sleep safety behaviors, for instance through behavioral experiments.

Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men.

PubMed

Ruige, Johannes B; Bekaert, Marlies; Lapauw, Bruno; Fiers, Tom; Lehr, Stefan; Hartwig, Sonja; Herzfeld de Wiza, Daniella; Schiller, Martina; Passlack, Waltraud; Van Nieuwenhove, Yves; Pattyn, Piet; Cuvelier, Claude; Taes, Youri E; Sell, Henrike; Eckel, Juergen; Kaufman, Jean-Marc; Ouwens, D Margriet

2012-07-01

Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men. The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines. Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches. Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1α, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo. Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.

Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies

PubMed Central

Pérez-Sánchez, Almudena; Micol, Vicente

2018-01-01

The skin is the body’s largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV) radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin. PMID:29587342

Impact of a pure reduction in heart rate for the treatment of left ventricular dysfunction: clinical benefits of ivabradine in the BEAUTIFUL trial.

PubMed

Danchin, Nicolas

2009-01-01

Ivabradine is an I(f) current inhibitor, that has documented antianginal efficacy. The BEAUTIFUL trial tested ivabradine against placebo in a large population of 10,917 patients in sinus rhythm, with coronary artery disease and left ventricular dysfunction, defined as left ventricular ejection fraction < or =35%. Overall, there was no impact of ivabradine on the primary end-point of the trial (cardiovascular mortality, hospitalisation for myocardial infarction, new onset or worsening heart failure). In the placebo arm of the trial, baseline heart rate > or = 70 bpm was associated with an increased risk of cardiovascular mortality, myocardial infarction, heart failure and coronary revascularisation. In the subgroup of patients with a baseline heart rate > or =70 bpm, treatment with ivabradine resulted in a significant, 36% reduction in the risk of myocardial infarction and a 20% reduction in the need for coronary revascularisation. Ivabradine was well tolerated, with an increased rate of treatment discontinuation, mainly due to bradycardia, compared with placebo. Because of its safety and efficacy to control angina, ivabradine should be considered first-line antianginal treatment in coronary artery disease patients with left ventricular dysfunction and increased heart rate, already receiving beta-blocker therapy or in whom these medications are not tolerated.

Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

PubMed Central

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called “pelvic organ” dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:21918729

Prior exercise and standing as strategies to circumvent sitting-induced leg endothelial dysfunction.

PubMed

Morishima, Takuma; Restaino, Robert M; Walsh, Lauren K; Kanaley, Jill A; Padilla, Jaume

2017-06-01

We have previously shown that local heating or leg fidgeting can prevent prolonged sitting-induced leg endothelial dysfunction. However, whether physical activity prevents subsequent sitting-induced leg endothelial dysfunction remains unknown. Herein, we tested the hypothesis that sitting-induced leg endothelial dysfunction would be prevented by prior exercise. We also examined if, in the absence of exercise, standing is an effective alternative strategy to sitting for conserving leg endothelial function. Fifteen young healthy subjects completed three randomized experimental trials: (1) sitting without prior exercise; (2) sitting with prior exercise; and (3) standing without prior exercise. Following baseline popliteal artery flow-mediated dilation (FMD) measurements, subjects maintained a supine position for 45 min in the sitting and standing trials, without prior exercise, or performed 45 min of leg cycling before sitting (i.e. sitting with prior exercise trial). Thereafter, subjects were positioned into a seated or standing position, according to the trial, for 3 h. Popliteal artery FMD measures were then repeated. Three hours of sitting without prior exercise caused a significant impairment in popliteal artery FMD (baseline: 3.8±0.5%, post-sitting: 1.5±0.5%, P <0.05), which was prevented when sitting was preceded by a bout of cycling exercise (baseline: 3.8±0.5%, post-sitting: 3.6±0.7%, P >0.05). Three hours of standing did not significantly alter popliteal artery FMD (baseline: 4.1±0.4%, post-standing: 4.3±0.4%, P >0.05). In conclusion, prolonged sitting-induced leg endothelial dysfunction can be prevented by prior aerobic exercise. In addition, in the absence of exercise, standing represents an effective substitute to sitting for preserving leg conduit artery endothelial function. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Qualitative study of sexual functioning in couples with erectile dysfunction: prospective evaluation of the thermography diagnostic system.

PubMed

Ng, Wan Kee; Ng, Yin Kwee; Tan, Yung Khan

2009-01-01

To evaluate the prospective use of the thermography diagnostic system in assessing sexual function in patients with erectile dysfunction (ED). Thermographs were taken on 14 subjects in a clinical trial conducted at Tan Tock Seng Hospital. After a thorough clinical interview with a standardized questionnaire, patients were scanned for baseline temperature profile before being given an oral dose of sildenafil 100 mg. Subjects were scanned again in the same setting an hour later. If so desired, subjects were given visual stimulation and were allowed minimum direct stimulation, excluding the penis, to elicit erection. Temperature profiles were analyzed using the thermography analysis software in the VarioCAM camera. Three representative cases are presented to illustrate the potential for using the Infrared thermography (IR) diagnostic system in differentiating psychogenic ED. IR was able to capture a significant difference in blood flow to the corpus cavernosum. Subjects with psychogenic ED have higher surface temperatures (34.3 degrees C +/- 0.71 in the flaccid state and 35.3 degrees C +/- 0.2 during erection) compared to subjects with organic ED (33.64 degrees C +/- 0.4 in flaccid and 33.55 degrees C +/- 0.91 during erection). The difference in surface temperature between flaccid and erected states in subjects with organic ED was not significant. The proposed diagnostic test based on IR has tremendous clinical potential in differentiating psychogenic ED from organic ED. IR could potentially be a portable, noninvasive and convenient adjunct in the diagnosis and management of ED.

Fibromyalgia Syndrome Module at OMERACT 9

PubMed Central

Mease, Philip; Arnold, Lesley M; Choy, Ernest H; Clauw, Daniel J.; Crofford, Leslie; Glass, Jennifer M; Martin, Susan A; Morea, Jessica; Simon, Lee; Strand, Vibeke; Williams, David A

2012-01-01

Objectives (1) Establish a core domain set for fibromyalgia (FM) assessment in clinical trials and practice, (2) review outcome measures’ performance characteristics, (3) discuss development of a responder index for the assessment of FM in clinical trials, (4) review objective markers, (5) review the domain of cognitive dysfunction, (6) establish a research agenda for work regarding outcomes research. Methods (1) Results of univariate and multivariate analysis of 10 different FM clinical trials of four different drugs, mapping key domains identified in previously presented patient focus group: Delphi exercises and a clinician/researcher Delphi exercise, breakout discussions to vote on possible essential domains and reliable measures. (2) Updates presented regarding outcome measures’ status. (3) Presented update on objective markers to measure FM disease state. 4) The issue of cognitive dysfunction (dyscognition) in FM was reviewed. Results (1) Greater than 70% of OMERACT participants agreed that pain, tenderness, fatigue, patient global, multidimensional function and sleep disturbance domains should be measured in all FM clinical trials, dyscognition and depression in some trial, and domains of research interest include stiffness, anxiety, functional imaging, and cerebrospinal fluid biomarkers. (2) FM domains’ outcome measures have generally proven to be reliable, discriminative, and feasible. More sophisticated and comprehensive measures are in development, as is a responder index for FM. (3) Increasing number of objective markers are being developed for FM assessment. (4) Cognitive dysfunction assessment by self-assessed and applied outcome measures is being developed. Conclusions A multidimensional symptom core set is proposed for the evaluation of FM in clinical trials. There is ongoing research on improved measures of single domains and composite measures. PMID:19820221

Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies.

PubMed

Doctor, Allan; Zimmerman, Jerry; Agus, Michael; Rajasekaran, Surender; Bubeck Wardenburg, Juliane; Fortenberry, James; Zajicek, Anne; Mairson, Emma; Typpo, Katri

2017-03-01

To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). Literature review, research data, and expert opinion. Not applicable. Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities. Summary of presentations and discussion supported and supplemented by relevant literature. Among critically ill children, multiple organ dysfunction syndrome is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this article, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of multiple organ dysfunction syndrome. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anticytokine therapies, antitoxin treatments, antioxidant approaches, and multiple forms of exogenous steroids. For the field to advance, promising therapies and other therapies must be assessed in rigorous manner and implemented accordingly.

A double-blind placebo-controlled trial of maca root as treatment for antidepressant-induced sexual dysfunction in women.

PubMed

Dording, Christina M; Schettler, Pamela J; Dalton, Elizabeth D; Parkin, Susannah R; Walker, Rosemary S W; Fehling, Kara B; Fava, Maurizio; Mischoulon, David

2015-01-01

Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD) in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) in 45 female outpatients (mean age of 41.5 ± 12.5 years) with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women) were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score ≤ 10 (9.5% for maca versus 4.8% for placebo), attaining an MGH-SFQ score ≤ 12 (30.0% for maca versus 20.0% for placebo) and reaching an MGH-SFQ score ≤ 8 (9.5% for maca versus 5.0% for placebo). Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126.

A Double-Blind Placebo-Controlled Trial of Maca Root as Treatment for Antidepressant-Induced Sexual Dysfunction in Women

PubMed Central

Dording, Christina M.; Schettler, Pamela J.; Dalton, Elizabeth D.; Parkin, Susannah R.; Walker, Rosemary S. W.; Fehling, Kara B.; Fava, Maurizio

2015-01-01

Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD) in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) in 45 female outpatients (mean age of 41.5 ± 12.5 years) with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women) were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score ≤ 10 (9.5% for maca versus 4.8% for placebo), attaining an MGH-SFQ score ≤ 12 (30.0% for maca versus 20.0% for placebo) and reaching an MGH-SFQ score ≤ 8 (9.5% for maca versus 5.0% for placebo). Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126. PMID:25954318

Pharmacotherapy of Sexual Dysfunctions : Current Status

PubMed Central

Avasthi, Ajith; Biswas, Parthasarathy

2004-01-01

The sexual dysfunctions are one of the most prevalent conditions. Sexual dysfunctions can have profound effect on the psychological well-being of an individual and the psychosexual relationship of a couple. Management of the sexual dysfunction should be preceded by an accurate diagnosis reached after a complete medical and sexual history and physical examination. Current focus of researchers has been on understanding the pathophysiology of erectile dysfunction, premature ejaculation and other sexual dysfunctions that can help in developing newer pharmacological cures for these conditions. Recently, a number of clinical trials have studied the potential effectiveness of the phosphodiesterase (PDE)-5 inhibitor sildenafil in the treatment of Erectile Dysfunction (ED) and Premature Ejaculation (PME). The introduction of PDE-5 inhibitors like sildenafil, vardenafil and tadalafil has revolutionized the treatment of sexual dysfunctions. This review focuses on the recent pharmacological advances in the treatment of common sexual dysfunctions like ED and PME with special focus on the role of PDE-5 inhibitors. Also discussed is the pharmacological treatment of other less prevalent and recognized disorders like female sexual dysfunction, drug induced sexual dysfunction etc. PMID:21224902

Lactoferrin and lysozyme to reduce environmental enteric dysfunction and stunting in Malawian children: Study protocol for a randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Chronic childhood malnutrition, as manifested by stunted linear growth, remains a persistent barrier to optimal child growth and societal development. Environmental enteric dysfunction (EED) is a significant underlying factor in the causal pathway to stunting, delayed cognitive development, and ulti...

[Organ damage and cardiorenal syndrome in acute heart failure].

PubMed

Casado Cerrada, Jesús; Pérez Calvo, Juan Ignacio

2014-03-01

Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this syndrome. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Polycystic Ovary Syndrome: Effect and Mechanisms of Acupuncture for Ovulation Induction

PubMed Central

Johansson, Julia; Stener-Victorin, Elisabet

2013-01-01

Polycystic ovary syndrome (PCOS), the most common endocrine disorder among women of reproductive age, is characterized by the coexistence of hyperandrogenism, ovulatory dysfunction, and polycystic ovaries (PCO). PCOS also represents the largest part of female oligoovulatory infertility, and the management of ovulatory and menstrual dysfunction, comprises a third of the high costs of PCOS treatment. Current pharmacological and surgical treatments for reproductive symptoms are effective, however, associated with negative side effects, such as cardiovascular complications and multiple pregnancies. For menstrual irregularities and ovulation induction in women with PCOS, acupuncture has indicated beneficial effects. This review will focus on the results from randomized controlled acupuncture trials for regulation of menstrual dysfunction and for inducing ovulation in women with PCOS although there are uncontrolled trials with nonetheless interesting results. Animal experimental studies will be further discussed when they can provide a more mechanistic explanatory view. PMID:24073009

Effects of auto-servo ventilation on patients with sleep-disordered breathing, stable systolic heart failure and concomitant diastolic dysfunction: subanalysis of a randomized controlled trial.

PubMed

Birner, Christoph; Series, Frederic; Lewis, Keir; Benjamin, Amit; Wunderlich, Silke; Escourrou, Pierre; Zeman, Florian; Luigart, Ruth; Pfeifer, Michael; Arzt, Michael

2014-01-01

Systolic heart failure (HF) is frequently accompanied by diastolic dysfunction and sleep-disordered breathing (SDB). The objective of this subset analysis was to determine effect sizes of auto-servo ventilation (ASV and biphasic positive airway pressure ASV) on echocardiographic measures of diastolic function in patients with systolic HF and SDB. Thirty-two patients with stable systolic HF, concomitant diastolic dysfunction [age 66 ± 9 years old, left ventricular (LV) ejection fraction: 30 ± 7% and New York Heart Association class II: 72%] and SDB (apnea-hypopnea index, AHI: 48 ± 19/h; 53% had predominantly obstructive sleep apnea) receiving either ASV (n = 19) or optimal medical treatment (control, n = 13) were analyzed in a randomized controlled clinical trial. Polysomnographic and echocardiographic measurements were obtained at baseline and after 12 weeks. AHI significantly improved in the ASV group compared to the control group (-39 ± 18 vs. -0.2 ± 13.2/h, p < 0.001). At baseline, 24 (75%) patients had impaired LV relaxation, and 8 (25%) had a pseudo-normalized filling pattern. At the 12-week control visit, diastolic function assessed by the isovolumetric relaxation time (-10.3 ± 26.1 vs. 9.3 ± 49.1, p = 0.48) and deceleration time (-43.9 ± 88.8 vs. 12.4 ± 68.8, p = 0.40) tended to improve after ASV treatment, but did not reach statistical significance. Likewise, the proportion of patients whose diastolic dysfunction improved was nonsignificantly higher in the ASV than in the control group, respectively (37 vs. 15%, p = 0.25). ASV treatment efficiently abolishes SDB in patients with stable systolic HF and concomitant diastolic dysfunction, and was associated with a statistically nonsignificant improvement in measures of diastolic dysfunction. Thus, these data provide estimates of effect size and justify the evaluation of the effects of ASV on diastolic function in larger randomized controlled trials. Copyright © 2013 S. Karger AG, Basel.

Early Immune Function and Duration of Organ Dysfunction in Critically Ill Septic Children.

PubMed

Muszynski, Jennifer A; Nofziger, Ryan; Moore-Clingenpeel, Melissa; Greathouse, Kristin; Anglim, Larissa; Steele, Lisa; Hensley, Josey; Hanson-Huber, Lisa; Nateri, Jyotsna; Ramilo, Octavio; Hall, Mark W

2018-02-22

Late immune suppression is associated with nosocomial infection and mortality in septic adults and children. Relationships between early immune suppression and outcomes in septic children remain unclear. Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis/septic shock. Methods, Measurements and Main Results: Children aged < 18 years meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy controls were sampled once. Innate immune function was quantified by whole blood ex vivo lipopolysaccharide-induced TNFα production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFNγ production capacity. 102 septic children and 35 healthy children were enrolled. Compared to healthy children, septic children demonstrated lower LPS-induced TNFα production (p < 0.0001) and lower PHA-induced IFNγ production (p<0.0001). Among septic children, early innate and adaptive immune suppression were associated with greater number of days with multiple organ dysfunction (MODS) and greater number of days with any organ dysfunction. On multivariable analyses, early innate immune suppression remained independently associated with increased MODS days [aRR 1.2 (1.03, 1.5)] and organ dysfunction days [aRR 1.2 (1.1, 1.3)]. Critically ill children with severe sepsis or septic shock demonstrate early innate and adaptive immune suppression. Early suppression of both innate and adaptive immunity are associated with longer duration of organ dysfunction and may be useful markers to guide investigations of immunomodulatory therapies in septic children.

Protocolized Treatment Is Associated With Decreased Organ Dysfunction in Pediatric Severe Sepsis.

PubMed

Balamuth, Fran; Weiss, Scott L; Fitzgerald, Julie C; Hayes, Katie; Centkowski, Sierra; Chilutti, Marianne; Grundmeier, Robert W; Lavelle, Jane; Alpern, Elizabeth R

2016-09-01

To determine whether treatment with a protocolized sepsis guideline in the emergency department was associated with a lower burden of organ dysfunction by hospital day 2 compared to nonprotocolized usual care in pediatric patients with severe sepsis. Retrospective cohort study. Tertiary care children's hospital from January 1, 2012, to March 31, 2014. Patients older than 56 days old and younger than 18 years old with international consensus defined severe sepsis and who required PICU admission within 24 hours of emergency department arrival were included. The exposure was the use of a protocolized emergency department sepsis guideline. The primary outcome was complete resolution of organ dysfunction by hospital day 2. One hundred eighty nine subjects were identified during the study period. Of these, 121 (64%) were treated with the protocolized emergency department guideline and 68 were not. There were no significant differences between the groups in age, sex, race, number of comorbid conditions, emergency department triage level, or organ dysfunction on arrival to the emergency department. Patients treated with protocolized emergency department care were more likely to be free of organ dysfunction on hospital day 2 after controlling for sex, comorbid condition, indwelling central venous catheter, Pediatric Index of Mortality-2 score, and timing of antibiotics and IV fluids (adjusted odds ratio, 4.2; 95% CI, 1.7-10.4). Use of a protocolized emergency department sepsis guideline was independently associated with resolution of organ dysfunction by hospital day 2 compared to nonprotocolized usual care. These data indicate that morbidity outcomes in children can be improved with the use of protocolized care.

Corticosteroids and ARDS: A review of treatment and prevention evidence

PubMed Central

Khilnani, G.C.; Hadda, Vijay

2011-01-01

To systematically review the role of corticosteroids in prevention of acute respiratory distress syndrome (ARDS) in high-risk patients, and in treatment of established ARDS. Primary articles were identified by English-language Pubmed/MEDLINE, Cochrane central register of controlled trials, and Cochrane systemic review database search (1960–June 2009) using the MeSH headings: ARDS, adult respiratory distress syndrome, ARDS, corticosteroids, and methylprednisolone (MP). The identified studies were reviewed and information regarding role of corticosteroids in prevention and treatment of ARDS was evaluated. Nine trials have evaluated the role of corticosteroid drugs in management of ARDS at various stages. Of the 9, 4 trials evaluated role of corticosteroids in prevention of ARDS, while other 5 trials were focused on treatment after variable periods of onset of ARDS. Trials with preventive corticosteroids, mostly using high doses of MP, showed negative results with patients in treatment arm, showing higher mortality and rate of ARDS development. While trials of corticosteroids in early ARDS showed variable results, somewhat, favoring use of these agents to reduce associated morbidities. In late stage of ARDS, these drugs have no benefits and are associated with adverse outcome. Use of corticosteroids in patients with early ARDS showed equivocal results in decreasing mortality; however, there is evidence that these drugs reduce organ dysfunction score, lung injury score, ventilator requirement, and intensive care unit stay. However, most of these trials are small, having a significant heterogeneity regarding study design, etiology of ARDS, and dosage of corticosteroids. Further research involving large-scale trials on relatively homogeneous cohort is necessary to establish the role of corticosteroids for this condition. PMID:21712921

Control groups in recent septic shock trials: a systematic review.

PubMed

Pettilä, Ville; Hjortrup, Peter Buhl; Jakob, Stephan M; Wilkman, Erika; Perner, Anders; Takala, Jukka

2016-12-01

The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.

Fibromyalgia syndrome module at OMERACT 9: domain construct.

PubMed

Mease, Philip; Arnold, Lesley M; Choy, Ernest H; Clauw, Daniel J; Crofford, Leslie J; Glass, Jennifer M; Martin, Susan A; Morea, Jessica; Simon, Lee; Strand, C Vibeke; Williams, David A

2009-10-01

The objective of the module was to (1) establish a core domain set for fibromyalgia (FM) assessment in clinical trials and practice, (2) review outcome measure performance characteristics, (3) discuss development of a responder index for assessment of FM in clinical trials, (4) review objective markers, (5) review the domain of cognitive dysfunction, and (6) establish a research agenda for outcomes research. Presentations at the module included: (1) Results of univariate and multivariate analysis of 10 FM clinical trials of 4 drugs, mapping key domains identified in previous patient focus group: Delphi exercises and a clinician/researcher Delphi exercise, and breakout discussions to vote on possible essential domains and reliable measures; (2) Updates regarding outcome measure status; (3) Update on objective markers to measure FM disease state; and (4) Review of the issue of cognitive dysfunction (dyscognition) in FM. Consensus was reached as follows: (1) Greater than 70% of OMERACT participants agreed that pain, tenderness, fatigue, patient global, multidimensional function and sleep disturbance domains should be measured in all FM clinical trials; dyscognition and depression should be measured in some trials; and stiffness, anxiety, functional imaging, and cerebrospinal fluid biomarkers were identified as domains of research interest. (2) FM domain outcome measures have generally proven to be reliable, discriminative, and feasible. More sophisticated and comprehensive measures are in development, as is a responder index for FM. (3) Increasing numbers of objective markers are being developed for FM assessment. (4) Cognitive dysfunction assessment by self-assessed and applied outcome measures is being developed. In conclusion, a multidimensional symptom core set is proposed for evaluation of FM in clinical trials. Research on improved measures of single domains and composite measures is ongoing.

Increased intra-individual reaction time variability in cocaine-dependent subjects: role of cocaine-related cues.

PubMed

Liu, Shijing; Lane, Scott D; Schmitz, Joy M; Green, Charles E; Cunningham, Kathryn A; Moeller, F Gerard

2012-02-01

Neuroimaging data suggest that impaired performance on response inhibition and information processing tests in cocaine-dependent subjects is related to prefrontal and frontal cortical dysfunction and that dysfunction in these brain areas may underlie some aspects of cocaine addiction. In subjects with attention-deficit hyperactivity disorder and other psychiatric disorders, the Intra-Individual Reaction Time Variability (IIRTV) has been associated with frontal cortical dysfunction. In the present study, we evaluated IIRTV parameters in cocaine-dependent subjects vs. controls using a cocaine Stroop task. Fifty control and 123 cocaine-dependent subjects compiled from three studies completed a cocaine Stroop task. Standard deviation (SD) and coefficient of variation (CV) for reaction times (RT) were calculated for both trials with neutral and trials with cocaine-related words. The parameters mu, sigma, and tau were calculated using an ex-Gaussian analysis employed to characterize variability in RTs. The ex-Gaussian analysis divides the RTs into normal (mu, sigma) and exponential (tau) components. Using robust regression analysis, cocaine-dependent subjects showed greater SD, CV and Tau on trials with cocaine-related words compared to controls (p<0.05). However, in trials with neutral words, there was no evidence of group differences in any IIRTV parameters (p>0.05). The Wilcoxon matched-pairs signed-rank test showed that for cocaine-dependent subjects, both SD and tau were larger in trials with cocaine-related words than in trials with neutral words (p<0.05). The observation that only cocaine-related words increased IIRTV in cocaine-dependent subjects suggests that cocaine-related stimuli might disrupt information processing subserved by prefrontal and frontal cortical circuits. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials

PubMed Central

Marzetti, Emanuele; Calvani, Riccardo; Cesari, Matteo; Buford, Thomas W.; Lorenzi, Maria; Behnke, Bradley J.; Leeuwenburgh, Christiaan

2013-01-01

Sarcopenia, the age-related loss of muscle mass and function, imposes a dramatic burden on individuals and society. The development of preventive and therapeutic strategies against sarcopenia is therefore perceived as an urgent need by health professionals and has instigated intensive research on the pathophysiology of this syndrome. The pathogenesis of sarcopenia is multifaceted and encompasses lifestyle habits, systemic factors (e.g., chronic inflammation and hormonal alterations), local environment perturbations (e.g., vascular dysfunction), and intramuscular specific processes. In this scenario, derangements in skeletal myocyte mitochondrial function are recognized as major factors contributing to the age-dependent muscle degeneration. In this review, we summarize prominent findings and controversial issues on the contribution of specific mitochondrial processes – including oxidative stress, quality control mechanisms and apoptotic signaling – on the development of sarcopenia. Extramuscular alterations accompanying the aging process with a potential impact on myocyte mitochondrial function are also discussed. We conclude with presenting methodological and safety considerations for the design of clinical trials targeting mitochondrial dysfunction to treat sarcopenia. Special emphasis is placed on the importance of monitoring the effects of an intervention on muscle mitochondrial function and identifying the optimal target population for the trial. PMID:23845738

Early initiation of beta blockade in heart failure: issues and evidence.

PubMed

Williams, Randall E

2005-09-01

Despite clinical trials demonstrating that inhibitors of the renin-angiotensin and sympathetic nervous systems can reduce the mortality and morbidity risk associated with heart failure, these drugs have remained underutilized in general clinical practice. In particular, many patients with heart failure due to left ventricular systolic dysfunction fail to receive beta blockers, although this class of drugs, as well as other antihypertensive agents such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, are recommended as part of routine heart failure therapy by national expert consensus guidelines. In-hospital initiation of beta-blocker therapy may improve long-term utilization by physicians and compliance by patients through obviating many of the misperceived dangers associated with beta blockade. The following review of the clinical trial data from the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, the Metoprolol Controlled-Release Randomized Intervention Trial in Heart Failure (MERIT-HF), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial, and the Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) trial on the efficacy, safety, and tolerability of beta blockers indicates that early initiation can be safely achieved and can improve patient outcomes.

Common beans and cowpeas as complementary foods to reduce environmental enteric dysfunction and stunting in Malawian children: Study protocol for two randomized controlled trials

USDA-ARS?s Scientific Manuscript database

Interventions to decrease the burden of childhood malnutrition are urgently needed, as millions of children die annually owing to undernutrition and hundreds of millions more are left cognitively and physically stunted. Environmental enteric dysfunction (EED), a pervasive chronic subclinical inflamm...

The diagnosis and management of progressive dysfunction of health care organizations.

PubMed

Chervenak, Frank A; McCullough, Laurence B

2005-04-01

This paper presents an ethically justified approach to the diagnosis and management of progressive dysfunction of health care organizational cultures. We explain the concept of professional integrity in terms of the ethical concept of the cofiduciary responsibility of physicians and health care organizations. We identify the ethical features of a healthy health care organization and the spectrum of progressive dysfunction of organizational cultures from cynical through wonderland and Kafkaesque to postmodern. Physicians should respond to cynical health care organizations by creating moral enclaves of professional integrity for the main purpose of confrontation and reform, to wonderland organizations by strengthening moral enclaves for the main purpose of resisting self-deception, to Kafkaesque organizations by strengthening moral enclaves still further for the main purpose of defending professional integrity (adopting a Machiavellian appearance of virtue as necessary), and to postmodern organizations by creating moral fortresses and, should these fail, quitting.

Cognitive dysfunction in depression - pathophysiology and novel targets.

PubMed

Carvalho, Andre F; Miskowiak, Kamilla K; Hyphantis, Thomas N; Kohler, Cristiano A; Alves, Gilberto S; Bortolato, Beatrice; G Sales, Paulo Marcelo; Machado-Vieira, Rodrigo; Berk, Michael; McIntyre, Roger S

2014-01-01

Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

Frankenswine, or bringing home the bacon

PubMed Central

2008-01-01

Xenotransplantation—specifically from pig into human—could resolve the critical shortage of organs, tissues and cells for clinical transplantation. Genetic engineering techniques in pigs are relatively well-developed and to date have largely been aimed at producing pigs that either (1) express high levels of one or more human complement-regulatory protein(s), such as decay-accelerating factor or membrane cofactor protein, or (2) have deletion of the gene responsible for the expression of the oligosaccharide, Galα1,3Gal (Gal), the major target for human anti-pig antibodies, or (3) have both manipulations. Currently the transplantation of pig organs in adequately-immunosuppressed baboons results in graft function for periods of 2–6 months (auxiliary hearts) and 2–3 months (life-supporting kidneys). Pig islets have maintained normoglycemia in diabetic monkeys for >6 months. The remaining immunologic barriers to successful xenotransplantation are discussed, and brief reviews made of (1) the potential risk of the transmission of an infectious microorganism from pig to patient and possibly to the public at large, (2) the potential physiologic incompatibilities between a pig organ and its human counterpart, (3) the major ethical considerations of clinical xenotransplantation, and (4) the possible alternatives that compete with xenotransplantation in the field of organ or cell replacement, such as mechanical devices, tissue engineering, stem cell biology and organogenesis. Finally, the proximity of clinical trials is discussed. Islet xenotransplantation is already at the stage where clinical trials are actively being considered, but the transplantation of pig organs will probably require further genetic modifications to be made to the organ-source pigs to protect their tissues from the coagulation/anticoagulation dysfunction that plays a significant role in pig graft failure after transplantation in primates. PMID:19279708

Bioactivation of organic nitrates and the mechanism of nitrate tolerance.

PubMed

Klemenska, Emila; Beresewicz, Andrzej

2009-01-01

Organic nitrates, such as nitroglycerin, are commonly used in the therapy of cardiovascular disease. Long-term therapy with these drugs, however, results in the rapid development of nitrate tolerance, limiting their hemodynamic and anti-ischemic efficacy. In addition, nitrate tolerance is associated with the expression of potentially deleterious modifications such as increased oxidative stress, endothelial dysfunction, and sympathetic activation. In this review we discuss current concepts regarding the mechanisms of organic nitrate bioactivation, nitrate tolerance, and nitrate-mediated oxidative stress and endothelial dysfunction. We also examine how hydralazine may prevent nitrate tolerance and related endothelial dysfunction.

Comparison effect of physiotherapy with surgery on sexual function in patients with pelvic floor disorder: A randomized clinical trial

PubMed Central

Eftekhar, Tahereh; Sohrabi, Maryam; Haghollahi, Fedyeh; Shariat, Mamak; Miri, Elahe

2014-01-01

Background: Female sexual dysfunction is a common problem among general population, especially in urogynecological patient, and can lead to a decrease in quality of life and affect martial relationship. Objective: This study was compared the effect of surgical methods versus physiotherapy on sexual function in pelvic floor disorder. Materials and Methods: This randomized controlled trial was performed in Urogynecology clinic since August 2007 to December 2009 on 90 patients aged from 25-55 years with previous delivery, positive history of sexual dysfunction with stage <3 of pelvic organ prolapsed and divided in two groups. Group A (n=45) received standard rectocele repair and prineorrhaphy, group B (n=45) received physiotherapy for eight weeks twice a week (electrical stimulation, Kegel exercises). The female sexual function index (FSFI) used to evaluate the sexual function in cases before and after intervention. Frequency of variable scores (libido, orgasm, dysparunia) included without disorder, frequently good, sometimes good, very much and extreme were compared between two groups. Results: Libido and arousal were improved in both groups (p=0.007, p=0.001 respectively). Orgasm and dyspareunia were improved in group B (p=0.001). Dysparunia was more painful in group A. There was significant difference between two groups (improvement of orgasm and dysparunia in group B) (p=0.001). Conclusion: It seems that physiotherapy is an appropriate method for treatment of sexual disorder in pelvic floor disorder. Registration ID in IRCT: IRCT2013031112790N1. PMID:24799856

Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis.

PubMed

Maestraggi, Quentin; Lebas, Benjamin; Clere-Jehl, Raphaël; Ludes, Pierre-Olivier; Chamaraux-Tran, Thiên-Nga; Schneider, Francis; Diemunsch, Pierre; Geny, Bernard; Pottecher, Julien

2017-01-01

Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF) at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called "cytopathic hypoxia," perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs). In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system ("immunoparalysis") translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

Quality in Acute Stroke Care (QASC): process evaluation of an intervention to improve the management of fever, hyperglycemia, and swallowing dysfunction following acute stroke.

PubMed

Drury, Peta; Levi, Christopher; D'Este, Catherine; McElduff, Patrick; McInnes, Elizabeth; Hardy, Jennifer; Dale, Simeon; Cheung, N Wah; Grimshaw, Jeremy M; Quinn, Clare; Ward, Jeanette; Evans, Malcolm; Cadilhac, Dominique; Griffiths, Rhonda; Middleton, Sandy

2014-08-01

Our randomized controlled trial of a multifaceted evidence-based intervention for improving the inpatient management of fever, hyperglycemia, and swallowing dysfunction in the first three-days following stroke improved outcomes at 90 days by 15%. We designed a quantitative process evaluation to further explain and illuminate this finding. Blinded retrospective medical record audits were undertaken for patients from 19 stroke units prior to and following the implementation of three multidisciplinary evidence-based protocols (supported by team-building workshops, and site-based education and support) for the management of fever (temperature ≥37·5°C), hyperglycemia (glucose >11 mmol/l), and swallowing dysfunction in intervention stroke units. Data from 1804 patients (718 preintervention; 1086 postintervention) showed that significantly more patients admitted to hospitals allocated to the intervention group received care according to the fever (n = 186 of 603, 31% vs. n = 74 of 483, 15%, P < 0·001), hyperglycemia (n = 22 of 603, 3·7% vs. n = 3 of 483, 0·6%, P = 0·01), and swallowing dysfunction protocols (n = 241 of 603, 40% vs. n = 19 of 483, 4·0%, P ≤ 0·001). Significantly more patients in these intervention stroke units received four-hourly temperature monitoring (n = 222 of 603, 37% vs. n = 90 of 483, 19%, P < 0·001) and six-hourly glucose monitoring (194 of 603, 32% vs. 46 of 483, 9·5%, P < 0·001) within 72 hours of admission to a stroke unit, and a swallowing screen (242 of 522, 46% vs. 24 of 350, 6·8%, P ≤ 0·0001) within the first 24 hours of admission to hospital. There was no difference between the groups in the treatment of patients with fever with paracetamol (22 of 105, 21% vs. 38 of 131, 29%, P = 0·78) or their hyperglycemia with insulin (40 of 100, 40% vs. 17 of 57, 30%, P = 0·49). Our intervention resulted in better protocol adherence in intervention stroke units, which explains our main trial findings of improved patient 90-day outcomes. Although monitoring practices significantly improved, there was no difference between the groups in the treatment of fever and hyperglycemia following acute stroke. A significant link between improved treatment practices and improved outcomes would have explained further the success of our intervention, and we are still unable to explain definitively the large improvements in death and dependency found in the main trial results. One potential explanation is that improved monitoring may have led to better overall surveillance of deteriorating patients and faster initiation of treatments not measured as part of the main trial. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

The ICU trial: a new admission policy for cancer patients requiring mechanical ventilation.

PubMed

Lecuyer, Lucien; Chevret, Sylvie; Thiery, Guillaume; Darmon, Michael; Schlemmer, Benoît; Azoulay, Elie

2007-03-01

Cancer patients requiring mechanical ventilation are widely viewed as poor candidates for intensive care unit (ICU) admission. We designed a prospective study evaluating a new admission policy titled The ICU Trial. Prospective study. Intensive care unit. One hundred eighty-eight patients requiring mechanical ventilation and having at least one other organ failure. Over a 3-yr period, all patients with hematologic malignancies or solid tumors proposed for ICU admission underwent a triage procedure. Bedridden patients and patients in whom palliative care was the only cancer treatment option were not admitted to the ICU. Patients at earliest phase of the malignancy (diagnosis < 30 days) were admitted without any restriction. All other patients were prospectively included in The ICU Trial, consisting of a full-code ICU admission followed by reappraisal of the level of care on day 5. Among the 188 patients, 103 survived the first 4 ICU days and 85 died from the acute illness. Hospital survival was 21.8% overall. Among the 103 survivors on day 5, none of the characteristics of the malignancy were significantly different between the 62 patients who died and the 41 who survived. Time course of organ dysfunction over the first 6 ICU days differed significantly between survivors and nonsurvivors. Organ failure scores were more accurate on day 6 than at admission or on day 3 for predicting survival. All patients who required initiation of mechanical ventilation, vasopressors, or dialysis after 3 days in the ICU died. Survival was 40% in mechanically ventilated cancer patients who survived to day 5 and 21.8% overall. If these results are confirmed in future interventional studies, we recommend ICU admission with full-code management followed by reappraisal on day 6 in all nonbedridden cancer patients for whom lifespan-extending cancer treatment is available.

Effectiveness of physical exam signs for early detection of critical illness in pediatric systemic inflammatory response syndrome.

PubMed

Scott, Halden F; Donoghue, Aaron J; Gaieski, David F; Marchese, Ronald F; Mistry, Rakesh D

2014-11-19

Early detection of compensated pediatric septic shock requires diagnostic tests that are sensitive and specific. Four physical exam signs are recommended for detecting pediatric septic shock prior to hypotension (cold extremities, mental status, capillary refill, peripheral pulse quality); this study tested their ability to detect patients who develop organ dysfunction among a cohort of undifferentiated pediatric systemic inflammatory response syndrome patients. A prospective cohort of 239 pediatric emergency department patients <19 years with fever and tachycardia and undergoing phlebotomy were enrolled. Physicians recorded initial physical exams on a standardized form. Abstraction of the medical record determined outcomes including organ dysfunction, intensive care unit stay, serious bacterial infection, and therapies. Organ dysfunction occurred in 13/239 (5.4%) patients. Presence of at least one sign was significantly associated with organ dysfunction (Relative Risk: 2.71, 95% CI: 1.05-6.99), and presence of at least two signs had a Relative Risk = 4.98 (95% CI: 1.82-13.58). The sensitivity of exam findings ranged from 8-54%, specificity from 84-98%. Signs were associated with increased risk of intensive care and fluid bolus, but not with serious bacterial infection, intravenous antibiotics or admission. Altered mental status and peripheral pulse quality were significantly associated with organ dysfunction, while abnormal capillary refill time and presence of cold, mottled extremities were not. Certain recommended physical exam signs were associated with increased risk of organ dysfunction, a rare outcome in this undifferentiated pediatric population with fever and tachycardia. Sensitivity was low, while specificity was high. Additional research into optimally sensitive and specific diagnostic strategies is needed.

Immune thrombocytopenia with multi-organ dysfunction syndrome as a rare presentation of scrub typhus: a case report.

PubMed

Ittyachen, Abraham M; Abraham, Saramma P; Krishnamoorthy, Smitha; Vijayan, Anuroopa; Kokkat, Jayamohan

2017-10-06

Scrub typhus is an acute infectious illness caused by Orientia tsutsugamushi. It is endemic to a part of the world known as the "tsutsugamushi triangle". Humans are accidental hosts in this zoonotic disease. About a third of patients admitted with scrub typhus have evidence of multi-organ dysfunction. Multi-organ dysfunction secondary to scrub typhus carries a high mortality rate. We report a 65-year old lady who was admitted in a Tertiary Care Center in the state of Kerala in India, with 7 day history of fever, myalgia and reduced urine output. Head to foot examination revealed the presence of an eschar on her chest. One week prior to the onset of her illness she had gone trekking through a hilly forest area. She was clinically suspected to have scrub typhus, which was later confirmed with laboratory tests. She developed multi-organ dysfunction syndrome secondary to this illness. Though there was an improvement in the multi-organ dysfunction, thrombocytopenia alone failed to improve. Bone marrow study was done which was suggestive of immune thrombocytopenia. Patient was given a course of steroids with which the thrombocytopenia improved. Failure of platelet count to normalize even after there has been a general improvement of other markers of multi-organ dysfunction in scrub typhus should prompt the clinician to consider other potential causes of thrombocytopenia. An unusual finding as this calls for further research to understand the molecular mechanisms behind such an event. Further, considering the close similarity in clinical presentation of several tropical illnesses, meticulous history taking and a detailed physical examination needs to be emphasized.

A comparison of three organ dysfunction scores: MODS, SOFA and LOD for predicting ICU mortality in critically ill patients.

PubMed

Khwannimit, Bodin

2007-06-01

To compare the validity of the Multiple Organ Dysfunction Score (MODS), Sequential Organ Failure Assessment (SOFA), and Logistic Organ Dysfunction Score (LOD) for predicting ICU mortality of Thai critically ill patients. A retrospective study was made of prospective data collected between the 1st July 2004 and 31st March 2006 at Songklanagarind Hospital. One thousand seven hundred and eighty two patients were enrolled in the present study. Two hundred and ninety three (16.4%) deaths were recorded in the ICU. The areas under the Receiver Operating Curves (A UC) for the prediction of ICU mortality the results were 0.861 for MODS, 0.879 for SOFA and 0.880 for LOD. The AUC of SOFA and LOD showed a statistical significance higher than the MODS score (p = 0.014 and p = 0.042, respectively). Of all the models, the neurological failure score showed the best correlation with ICU mortality. All three organ dysfunction scores satisfactorily predicted ICU mortality. The LOD and neurological failure had the best correlation with ICU outcome.

Continuous hemoadsorption with a cytokine adsorber during sepsis - a review of the literature.

PubMed

Houschyar, Khosrow S; Pyles, Malcolm N; Rein, Susanne; Nietzschmann, Ina; Duscher, Dominik; Maan, Zeshaan N; Weissenberg, Kristian; Philipps, Hubertus M; Strauss, Catharina; Reichelt, Beate; Siemers, Frank

2017-05-29

Sepsis is a well-recognized healthcare issue worldwide, ultimately resulting in significant mortality, morbidity and resource utilization during and after critical illness. In its most severe form, sepsis causes multi-organ dysfunction that produces a state of critical illness characterized by severe immune dysfunction and catabolism. Sepsis induces the activation of complement factor via 3 pathways and the release of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β), resulting in a systemic inflammatory response. The inflammatory cytokines and nitric oxide release induced by sepsis decrease systemic vascular resistance, resulting in profound hypotension. The combination of hypotension and microvascular occlusion results in tissue ischemia and ultimately leads to multiple organ failure. Several clinical and experimental studies have reported that treatment using adsorption of cytokines is beneficial during endotoxemia and sepsis. This review article analyzes the efficacy of CytoSorb® adsorber in reducing the inflammatory response during sepsis. The CytoSorb® adsorber is known to have excellent adsorption rates for inflammatory cytokines such as IL-1β, IL-6, IL-8, IL-10, and TNF-α. Studies have demonstrated that treatment with cytokine adsorbing columns has beneficial effects on the survival rate and inflammatory responses in animal septic models. Additionally, several cases have been reported in which treatment with cytokine adsorbing columns is very effective in hemodynamic stabilization and in preventing organ failure in critically ill patients. Although further investigations and clinical trials are needed, treatment with cytokine adsorbing columns may play an important role in the treatment of sepsis in the near future.

Quantification of Postmembrane Gaseous Microembolization During Venoarterial Extracorporeal Membrane Oxygenation.

PubMed

Jiao, York; Gipson, Keith E; Bonde, Pramod; Mangi, Abeel; Hagberg, Robert; Rosinski, David J; Gross, Jeffrey B; Schonberger, Robert B

Prolonged use of venoarterial extracorporeal membrane oxygenation (VA ECMO) may be complicated by end-organ dysfunction. Although gaseous microemboli (GME) are thought to damage end organs during cardiopulmonary bypass, patient exposures to GME have not been well characterized during VA ECMO. We therefore performed an observational study of GME in adult VA ECMO patients, with correlation to clinical events during routine patient care. After institutional review board (IRB) approval, we used two Doppler probes to detect GME noninvasively in extracorporeal membrane oxygenation (ECMO) circuits on four patients for 15 hours total while also recording patient care events. We then conducted in vitro trials to compare Doppler signals with gold-standard measurements using an Emboli Detection and Classification EDAC quantifier (Luna Innnovations, Inc. Roanoke, VA) (Terumo Cardiovascular, Ann Arbor, MI) during simulated clinical interventions. Correlations between Doppler and EDAC data were used to estimate GME counts and volumes represented by clinical Doppler data. A total of 503 groups of Doppler peaks representing GME showers were observed, including 194 statistically larger showers during patient care activities containing 92% of total Doppler peaks. Intravenous injections accounted for an estimated 68% of GME and 88% of GME volume, whereas care involving movement accounted for an estimated 6% of GME and 3% of volume. Overall estimated embolic rates of 24,000 GME totaling 4 μl/hr rivals reported GME rates during cardiopulmonary bypass. Numerous GME are present in the postmembrane circuit during VA ECMO, raising concern for effects on microcirculation and organ dysfunction. Strategies to detect and minimize GME may be warranted to limit embolic exposures experienced by VA ECMO patients.

Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma

PubMed Central

Denk, Stephanie; Wiegner, Rebecca; Hönes, Felix M.; Messerer, David A. C.; Radermacher, Peter; Kalbitz, Miriam; Braumüller, Sonja; McCook, Oscar; Gebhard, Florian; Weckbach, Sebastian; Huber-Lang, Markus

2015-01-01

Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction. PMID:26556956

Functional Turnover: An Empirical Assessment.

DTIC Science & Technology

1981-08-01

assumption that turnover is invariably dysfunctional to the organization (Dalton & Todor , 1979; Dalton & Todor , in press (a), (b); Jeswald, 1974; Muchinsky...34voluntary" turnover (Dalton, Todor & Krackhardt, in press). Dysfunctional (cell C) - The individual wants to leave the organization but the organization...criticized (Dalton & Todor , 1979; Dalton & Todor . in press (a), (b); Muchinsky & Tuttle, 1979; Muchinsky & Morrow, in press; Staw, in press; Staw

Guidewire exchange vs new site placement for temporary dialysis catheter insertion in ICU patients: is there a greater risk of colonization or dysfunction?

PubMed

Coupez, Elisabeth; Timsit, Jean-François; Ruckly, Stéphane; Schwebel, Carole; Gruson, Didier; Canet, Emmanuel; Klouche, Kada; Argaud, Laurent; Bohe, Julien; Garrouste-Orgeas, Maïté; Mariat, Christophe; Vincent, François; Cayot, Sophie; Cointault, Olivier; Lepape, Alain; Darmon, Michael; Boyer, Alexandre; Azoulay, Elie; Bouadma, Lila; Lautrette, Alexandre; Souweine, Bertrand

2016-07-30

Intensive care unit (ICU) patients require dialysis catheters (DCs) for renal replacement therapy (RRT). They carry a high risk of developing end-stage renal disease, and therefore their vascular access must be preserved. Guidewire exchange (GWE) is often used to avoid venipuncture insertion (VPI) at a new site. However, the impact of GWE on infection and dysfunction of DCs in the ICU is unknown. Our aim was to compare the effect of GWE and VPI on DC colonization and dysfunction in ICU patients. Using data from the ELVIS randomized controlled trial (RCT) (1496 ICU adults requiring DC for RRT or plasma exchange) we performed a matched-cohort analysis. Cases were DCs inserted by GWE (n = 178). They were matched with DCs inserted by VPI. Matching criteria were participating centre, simplified acute physiology score (SAPS) II +/-10, insertion site (jugular or femoral), side for jugular site, and length of ICU stay before DC placement. We used a marginal Cox model to estimate the effect of DC insertion (GWE vs. VPI) on DC colonization and dysfunction. DC colonization rate was not different between GWE-DCs and VPI-DCs (10 (5.6 %) for both groups) but DC dysfunction was more frequent with GWE-DCs (67 (37.6 %) vs. 28 (15.7 %); hazard ratio (HR), 3.67 (2.07-6.49); p < 0.01). Results were similar if analysis was restricted to DCs changed for dysfunction. GWE for DCs in ICU patients, compared with VPI did not contribute to DC colonization or infection but was associated with more than twofold increase in DC dysfunction. This study is registered with ClinicalTrials.gov, number NCT00563342 . Registered 2 April 2009.

Current Experience in Testing Mitochondrial Nutrients in Disorders Featuring Oxidative Stress and Mitochondrial Dysfunction: Rational Design of Chemoprevention Trials

PubMed Central

Pagano, Giovanni; Aiello Talamanca, Annarita; Castello, Giuseppe; Cordero, Mario D.; d’Ischia, Marco; Gadaleta, Maria Nicola; Pallardó, Federico V.; Petrović, Sandra; Tiano, Luca; Zatterale, Adriana

2014-01-01

An extensive number of pathologies are associated with mitochondrial dysfunction (MDF) and oxidative stress (OS). Thus, mitochondrial cofactors termed “mitochondrial nutrients” (MN), such as α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and l-carnitine (CARN) (or its derivatives) have been tested in a number of clinical trials, and this review is focused on the use of MN-based clinical trials. The papers reporting on MN-based clinical trials were retrieved in MedLine up to July 2014, and evaluated for the following endpoints: (a) treated diseases; (b) dosages, number of enrolled patients and duration of treatment; (c) trial success for each MN or MN combinations as reported by authors. The reports satisfying the above endpoints included total numbers of trials and frequencies of randomized, controlled studies, i.e., 81 trials testing ALA, 107 reports testing CoQ10, and 74 reports testing CARN, while only 7 reports were retrieved testing double MN associations, while no report was found testing a triple MN combination. A total of 28 reports tested MN associations with “classical” antioxidants, such as antioxidant nutrients or drugs. Combinations of MN showed better outcomes than individual MN, suggesting forthcoming clinical studies. The criteria in study design and monitoring MN-based clinical trials are discussed. PMID:25380523

Inflammatory response and extracorporeal circulation.

PubMed

Kraft, Florian; Schmidt, Christoph; Van Aken, Hugo; Zarbock, Alexander

2015-06-01

Patients undergoing cardiac surgery with extracorporeal circulation (EC) frequently develop a systemic inflammatory response syndrome. Surgical trauma, ischaemia-reperfusion injury, endotoxaemia and blood contact to nonendothelial circuit compounds promote the activation of coagulation pathways, complement factors and a cellular immune response. This review discusses the multiple pathways leading to endothelial cell activation, neutrophil recruitment and production of reactive oxygen species and nitric oxide. All these factors may induce cellular damage and subsequent organ injury. Multiple organ dysfunction after cardiac surgery with EC is associated with an increased morbidity and mortality. In addition to the pathogenesis of organ dysfunction after EC, this review deals with different therapeutic interventions aiming to alleviate the inflammatory response and consequently multiple organ dysfunction after cardiac surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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 ...

Influence of experimental rat model of multiple organ dysfunction on cefepime and amikacin pharmacokinetics.

PubMed Central

Mimoz, O; Jacolot, A; Padoin, C; Quillard, J; Tod, M; Louchahi, K; Samii, K; Petitjean, O

1996-01-01

We adapted an experimental model of multiple organ dysfunction to study the alterations it induces in the pharmacology of cefepime and amikacin. The half-lives of both antibiotics were significantly prolonged because of nonsignificant enhancement of the volume of distribution and reduced renal elimination. In the presence of multiple organ dysfunction, the concentration of each antibiotic in the lungs, compared with that in the lungs of healthy controls, was significantly decreased, despite similar concentrations in plasma, indicating that the application of a standard antibiotic concentration in plasma could lead to underdosage in tissues during the initial days of therapy. PMID:8851623

Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial.

PubMed

Self, Wesley H; Semler, Matthew W; Bellomo, Rinaldo; Brown, Samuel M; deBoisblanc, Bennett P; Exline, Matthew C; Ginde, Adit A; Grissom, Colin K; Janz, David R; Jones, Alan E; Liu, Kathleen D; Macdonald, Stephen P J; Miller, Chadwick D; Park, Pauline K; Reineck, Lora A; Rice, Todd W; Steingrub, Jay S; Talmor, Daniel; Yealy, Donald M; Douglas, Ivor S; Shapiro, Nathan I

2018-05-09

Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Magnetic resonance imaging correlates of bee sting induced multiple organ dysfunction syndrome: A case report.

PubMed

Das, Sushant K; Zeng, Li-Chuan; Li, Bing; Niu, Xiang-Ke; Wang, Jing-Liang; Bhetuwal, Anup; Yang, Han-Feng

2014-09-28

Occasionally systemic complications with high risk of death, such as multiple organ dysfunction syndrome (MODS), can occur following multiple bee stings. This case study reports a patient who presented with MODS, i.e., acute kidney injury, hepatic and cardiac dysfunction, after multiple bee stings. The standard clinical findings were then correlated with magnetic resonance imaging (MRI) findings, which demonstrates that MRI may be utilized as a simpler tool to use than other multiple diagnostics.

Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG).

PubMed

Wang, Winfred C; Ware, Russell E; Miller, Scott T; Iyer, Rathi V; Casella, James F; Minniti, Caterina P; Rana, Sohail; Thornburg, Courtney D; Rogers, Zora R; Kalpatthi, Ram V; Barredo, Julio C; Brown, R Clark; Sarnaik, Sharada A; Howard, Thomas H; Wynn, Lynn W; Kutlar, Abdullah; Armstrong, F Daniel; Files, Beatrice A; Goldsmith, Jonathan C; Waclawiw, Myron A; Huang, Xiangke; Thompson, Bruce W

2011-05-14

Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects. This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin Sβ(0)thalassaemia, were aged 9-18 months at randomisation, and were not selected for clinical severity. Participants received liquid hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on (99)Tc spleen scan) and renal function (glomerular filtration rate by (99m)Tc-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every 2-4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00006400. 96 patients received hydroxycarbamide and 97 placebo, of whom 83 patients in the hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0·21; and a difference in the mean increase in DTPA glomerular filtration rate in the hydroxycarbamide group versus the placebo group of 2 mL/min per 1·73 m(2), p=0·84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0·002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p<0·0001), with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion. Hydroxyurea increased haemoglobin and fetal haemoglobin, and decreased white blood-cell count. Toxicity was limited to mild-to-moderate neutropenia. On the basis of the safety and efficacy data from this trial, hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia. The US National Heart, Lung, and Blood Institute; and the National Institute of Child Health and Human Development. Copyright © 2011 Elsevier Ltd. All rights reserved.

Low-intensity extracorporeal shock wave therapy for erectile dysfunction after radical prostatectomy: a review of preclinical studies.

PubMed

Zou, Zi-Jun; Liang, Jia-Yu; Liu, Zhi-Hong; Gao, Rui; Lu, Yi-Ping

2018-02-01

Low-intensity extracorporeal shock wave therapy (LI-ESWT) is a novel treatment for erectile dysfunction (ED). Its ability to improve erectile function has been shown in patients with vasculogenic ED by many randomized-controlled trials against sham procedures. However, the role of LI-ESWT in ED caused by radical prostatectomy (RP) is still questionable because this type of ED was excluded from nearly all clinical studies; it has been investigated in only a few small single-arm trials. This review summarizes preclinical studies on mechanisms of action of LI-ESWT for ED and neurological diseases to explore the potential of this treatment for nerve-impaired ED after RP.

Functional outcomes in pediatric severe sepsis: further analysis of the researching severe sepsis and organ dysfunction in children: a global perspective trial.

PubMed

Farris, Reid W D; Weiss, Noel S; Zimmerman, Jerry J

2013-11-01

To evaluate risk factors for poor functional outcome in 28-day survivors after an episode of severe sepsis. Retrospective cohort study examining data from the Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective trial (NCT00049764). One hundred and four pediatric centers in 18 countries. Children with severe sepsis who required both vasoactive-inotropic infusions and mechanical ventilation and who survived to 28 days (n = 384). None. Poor functional outcome was defined as a Pediatric Overall Performance Category score greater than or equal to 3 and an increase from baseline when measured 28 days after trial enrollment. Median Pediatric Overall Performance Category at enrollment was 1 (interquartile range, 1-2). Median Pediatric Overall Performance Category at 28 days was 2 (interquartile range, 1-4). Thirty-four percent of survivors had decline in their functional status at 28 days, and 18% were determined to have a "poor" functional outcome. Hispanic ethnicity was associated with poor functional outcome compared to the white referent group (risk ratio = 1.9; 95% CI: 1.0-3.0). Clinical factors associated with increased risk of poor outcome included CNS and intra-abdominal infection sources compared to the lung infection referent category (risk ratio = 3.3; 95% CI: 1.4-5.6 and 2.4; 95% CI: 1.0-4.5, respectively); a history of recent trauma (risk ratio = 3.9; 95% CI: 1.4-5.4); receipt of cardiopulmonary resuscitation prior to enrollment (risk ratio = 5.1; 95% CI: 2.9-5.7); and baseline Pediatric Risk of Mortality III score of 20-29 (risk ratio = 2.8; 95% CI: 1.2-5.2) and Pediatric Risk of Mortality III greater than or equal to 30 (risk ratio = 4.5; 95% CI: 1.6-8.0) compared to the referent group with Pediatric Risk of Mortality III scores of 0-9. In this sample of 28-day survivors of pediatric severe sepsis diminished functional status was common. This analysis provides evidence that particular patient characteristics and aspects of an individual's clinical course are associated with poor functional outcome 28 days after onset of severe sepsis. These characteristics may provide opportunity for intervention in order to improve functional outcome in pediatric patients with severe sepsis. Decline in functional status 28 days after onset of severe sepsis is a frequent and potentially clinically meaningful event. Utilization of functional status as the primary outcome in future pediatric sepsis clinical trials should be considered.

Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock

PubMed Central

2010-01-01

Background Lactate clearance, a surrogate for the magnitude and duration of global tissue hypoxia, is used diagnostically, therapeutically and prognostically. This study examined the association of early lactate clearance with selected inflammatory, coagulation, apoptosis response biomarkers and organ dysfunction scores in severe sepsis and septic shock. Methods Measurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3), and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment) were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED). Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED. Results Two-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p < 0.01). The mean levels of all biomarkers and organ dysfunction scores over 72 hours were significantly lower with higher lactate clearance quartiles (p < 0.01). There was a significant decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles (p < 0.01). Conclusions Early lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock. PMID:20181046

Validating the WHO maternal near miss tool: comparing high- and low-resource settings.

PubMed

Witteveen, Tom; Bezstarosti, Hans; de Koning, Ilona; Nelissen, Ellen; Bloemenkamp, Kitty W; van Roosmalen, Jos; van den Akker, Thomas

2017-06-19

WHO proposed the WHO Maternal Near Miss (MNM) tool, classifying women according to several (potentially) life-threatening conditions, to monitor and improve quality of obstetric care. The objective of this study is to analyse merged data of one high- and two low-resource settings where this tool was applied and test whether the tool may be suitable for comparing severe maternal outcome (SMO) between these settings. Using three cohort studies that included SMO cases, during two-year time frames in the Netherlands, Tanzania and Malawi we reassessed all SMO cases (as defined by the original studies) with the WHO MNM tool (five disease-, four intervention- and seven organ dysfunction-based criteria). Main outcome measures were prevalence of MNM criteria and case fatality rates (CFR). A total of 3172 women were studied; 2538 (80.0%) from the Netherlands, 248 (7.8%) from Tanzania and 386 (12.2%) from Malawi. Total SMO detection was 2767 (87.2%) for disease-based criteria, 2504 (78.9%) for intervention-based criteria and 1211 (38.2%) for organ dysfunction-based criteria. Including every woman who received ≥1 unit of blood in low-resource settings as life-threatening, as defined by organ dysfunction criteria, led to more equally distributed populations. In one third of all Dutch and Malawian maternal death cases, organ dysfunction criteria could not be identified from medical records. Applying solely organ dysfunction-based criteria may lead to underreporting of SMO. Therefore, a tool based on defining MNM only upon establishing organ failure is of limited use for comparing settings with varying resources. In low-resource settings, lowering the threshold of transfused units of blood leads to a higher detection rate of MNM. We recommend refined disease-based criteria, accompanied by a limited set of intervention- and organ dysfunction-based criteria to set a measure of severity.

Stem Cell Therapy for Erectile Dysfunction.

PubMed

Matz, Ethan L; Terlecki, Ryan; Zhang, Yuanyuan; Jackson, John; Atala, Anthony

2018-04-06

The prevalence of erectile dysfunction (ED) is substantial and continues to rise. Current therapeutics for ED consist of oral medications, intracavernosal injections, vacuum erection devices, and penile implants. While such options may manage the disease state, none of these modalities, however, restore function. Stem cell therapy has been evaluated for erectile restoration in animal models. These cells have been derived from multiple tissues, have varied potential, and may function via local engraftment or paracrine signaling. Bone marrow-derived stem cells (BMSC) and adipose-derived stem cells (ASC) have both been used in these models with noteworthy effects. Herein, we will review the pathophysiology of ED, animal models, current and novel stem-cell based therapeutics, clinical trials and areas for future research. The relevant literature and contemporary data using keywords, "stem cells and erectile dysfunction" was reviewed. Examination of evidence supporting the association between erectile dysfunction and adipose derived stem cells, bone marrow derived stem cells, placental stem cells, urine stem cells and stem cell therapy respectively. Placental-derived stem cells and urine-derived stem cells possess many similar properties as BMSC and ASC, but the methods of acquisition are favorable. Human clinical trials have already demonstrated successful use of stem cells for improvement of erectile function. The future of stem cell research is constantly being evaluated, although, the evidence suggests a place for stem cells in erectile dysfunction therapeutics. Matz EL, Terlecki R, Zhang Y, et al. Stem Cell Therapy for Erectile Dysfunction. Sex Med Rev 2018;XX:XXX-XXX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Identifying and Extinguishing Dysfunctional and Deadly Organizational Practices

ERIC Educational Resources Information Center

Mawhinney, Thomas C.

2009-01-01

It is possible to define an organization's culture in terms of its dominant behavioral practices and their molar consequences, from the shop floor to the executive suite (Redmon & Mason, 2001). Dysfunctional and potentially deadly practices (for the organization as a whole) can be "latent." They often go undetected until their…

Effect of chiropractic manipulation on vertical jump height in young female athletes with talocrural joint dysfunction: a single-blind randomized clinical pilot trial.

PubMed

Hedlund, Sofia; Nilsson, Hans; Lenz, Markus; Sundberg, Tobias

2014-02-01

The main objective of this pilot study was to explore the effect of chiropractic high-velocity, low-amplitude (HVLA) manipulation on vertical jump height in young female athletes with talocrural joint dysfunction. This was a randomized assessor-blind clinical pilot trial. Twenty-two female handball players with talocrural joint dysfunction were randomized to receive either HVLA manipulation (n = 11) or sham treatment (n = 11) once a week during a 3-week period. The main outcome was change in vertical jump height from baseline to follow-up within and between groups after 3 weeks. Nineteen athletes completed the study. After 3 weeks, the group receiving HVLA manipulation (n = 11) had a statistically significant mean (SD) improvement in vertical jump height of 1.07 (1.23) cm (P = .017). The sham treatment group (n = 8) improved their vertical jump height by 0.59 (2.03) cm (P = .436). The between groups' change was 0.47 cm (95% confidence interval, -1.31 to 2.26; P = .571) in favor of the group receiving HVLA manipulation. Blinding and sham procedures were feasible, and there were no reported adverse events. The results of this pilot study show that a larger-scale study is feasible. Preliminary results suggest that chiropractic HVLA manipulation may increase vertical jump height in young female athletes with talocrural joint dysfunction. However, the clinical result in favor of HVLA manipulation compared with sham treatment needs statistical confirmation in a larger randomized clinical trial. Copyright © 2014 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

Three-step management of pneumothorax: time for a re-think on initial management†

PubMed Central

Kaneda, Hiroyuki; Nakano, Takahito; Taniguchi, Yohei; Saito, Tomohito; Konobu, Toshifumi; Saito, Yukihito

2013-01-01

Pneumothorax is a common disease worldwide, but surprisingly, its initial management remains controversial. There are some published guidelines for the management of spontaneous pneumothorax. However, they differ in some respects, particularly in initial management. In published trials, the objective of treatment has not been clarified and it is not possible to compare the treatment strategies between different trials because of inappropriate evaluations of the air leak. Therefore, there is a need to outline the optimal management strategy for pneumothorax. In this report, we systematically review published randomized controlled trials of the different treatments of primary spontaneous pneumothorax, point out controversial issues and finally propose a three-step strategy for the management of pneumothorax. There are three important characteristics of pneumothorax: potentially lethal respiratory dysfunction; air leak, which is the obvious cause of the disease; frequent recurrence. These three characteristics correspond to the three steps. The central idea of the strategy is that the lung should not be expanded rapidly, unless absolutely necessary. The primary objective of both simple aspiration and chest drainage should be the recovery of acute respiratory dysfunction or the avoidance of respiratory dysfunction and subsequent complications. We believe that this management strategy is simple and clinically relevant and not dependent on the classification of pneumothorax. PMID:23117233

Behavior and Symptom Change Among Women Treated with Placebo for Sexual Dysfunction

PubMed Central

Bradford, Andrea; Meston, Cindy M.

2011-01-01

Introduction In clinical trials of drug treatments for women’s sexual dysfunction, placebo responses have often been substantial. However, little is known about the clinical significance, specificity, predictors, and potential mechanisms of placebo response in sexual dysfunction. Aim We aimed to determine the nature and predictors of sexual function outcomes in women treated with placebo for female sexual arousal disorder (FSAD). Methods We conducted a secondary analysis of data from the placebo arm of a 12-week, multisite, randomized controlled pharmaceutical trial for FSAD (N = 50). We analyzed the magnitude, domain specificity, and clinical significance of sexual function scores at baseline, 4, 8, and 12 weeks (post-treatment). We examined longitudinal change in sexual function outcomes as a function of several baseline variables (e.g., age, symptom-related distress) and in relation to changes in sexual behavior frequency during the trial. Main Outcome Measure Female Sexual Function Index total score. Results The magnitude of change at post-treatment was clinically significant in approximately one-third of placebo recipients. Effect sizes were similar across multiple aspects of sexual function. Symptom improvement was strongly related to the frequency of satisfying sexual encounters during treatment. However, the relationship between sexual encounter frequency and outcome varied significantly between participants. Conclusions A substantial number of women experienced clinically significant improvement in sexual function during treatment with placebo. Changes in sexual behavior during the trial, more so than participant age or symptom severity at baseline, appeared to be an important determinant of outcome. Contextual and procedural aspects of the clinical trial may have influenced outcomes in the absence of an active drug treatment. PMID:20849412

Evaluation of Tai Chi Yunshou exercises on community-based stroke patients with balance dysfunction: a study protocol of a cluster randomized controlled trial.

PubMed

Tao, Jing; Rao, Ting; Lin, Lili; Liu, Wei; Wu, Zhenkai; Zheng, Guohua; Su, Yusheng; Huang, Jia; Lin, Zhengkun; Wu, Jinsong; Fang, Yunhua; Chen, Lidian

2015-02-25

Balance dysfunction after stroke limits patients' general function and participation in daily life. Previous researches have suggested that Tai Chi exercise could offer a positive improvement in older individuals' balance function and reduce the risk of falls. But convincing evidence for the effectiveness of enhancing balance function after stroke with Tai Chi exercise is still inadequate. Considering the difficulties for stroke patients to complete the whole exercise, the current trial evaluates the benefit of Tai Chi Yunshou exercise for patients with balance dysfunction after stroke through a cluster randomization, parallel-controlled design. A single-blind, cluster-randomized, parallel-controlled trial will be conducted. A total of 10 community health centers (5 per arm) will be selected and randomly allocated into Tai Chi Yunshou exercise group or balance rehabilitation training group. Each community health centers will be asked to enroll 25 eligible patients into the trial. 60 minutes per each session, 1 session per day, 5 times per week and the total training round is 12 weeks. Primary and secondary outcomes will be measured at baseline and 4-weeks, 8-weeks, 12-weeks, 6-week follow-up, 12-week follow-up after randomization. Safety and economic evaluation will also be assessed. This protocol aims to evaluate the effectiveness of Tai Chi Yunshou exercise for the balance function of patients after stroke. If the outcome is positive, this project will provide an appropriate and economic balance rehabilitation technology for community-based stroke patients. Chinese Clinical Trial Registry: ChiCTR-TRC-13003641. Registration date: 22 August, 2013 http://www.chictr.org/usercenter/project/listbycreater.aspx .

A Network Meta-Analysis Comparing Effects of Various Antidepressant Classes on the Digit Symbol Substitution Test (DSST) as a Measure of Cognitive Dysfunction in Patients with Major Depressive Disorder.

PubMed

Baune, Bernhard T; Brignone, Mélanie; Larsen, Klaus Groes

2018-02-01

Major depressive disorder is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis were carried out to assess the relative effect of antidepressants on cognitive dysfunction in major depressive disorder. MEDLINE, Embase, Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant conference abstracts were searched for randomized controlled trials assessing the effects of antidepressants/placebo on cognition. A network meta-analysis comparing antidepressants was conducted using a random effects model. The database search retrieved 11337 citations, of which 72 randomized controlled trials from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test, which targets multiple domains of cognition and is recognized as being sensitive to change, was the only test that was used across 12 of the included randomized controlled trials and that allowed the construction of a stable network suitable for the network meta-analysis. The interventions assessed included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the Digit Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI = 0.120; 0.529, P=.009}. Compared with other antidepressants, vortioxetine was statistically more efficacious on the Digit Symbol Substitution Test vs escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and tricyclic antidepressant classes. This study highlighted the large variability in measures used to assess cognitive functioning. The findings on the Digit Symbol Substitution Test indicate differential effects of various antidepressants on improving cognitive function in patients with major depressive disorder. © The Author 2017. Published by Oxford University Press on behalf of CINP.

In men with erectile dysfunction, satisfaction with quality of erections correlates with erection hardness, treatment satisfaction, and emotional well-being.

PubMed

Kaminetsky, Jed C; Depko, Andrzej J; Ströberg, Peter; Buvat, Jacques; Tseng, Li-Jung; Stecher, Vera J

2009-03-01

The validated Quality of Erection Questionnaire (QEQ) evaluates satisfaction with erection quality. To collate QEQ data, including correlations between QEQ outcomes and outcomes assessing emotional well-being, treatment satisfaction, and erection hardness after sildenafil citrate treatment. In four trials, men older than 18 years and with erectile dysfunction, a stable sexual partner, and no recent phosphodiesterase type 5 inhibitor use were randomized to double-blind flexible-dose sildenafil or placebo (1:1 ratio) for 6 or 10 weeks (two trials), fixed-dose 50 mg, 100 mg, and placebo (1:1:1 ratio) for 8 weeks (one trial), and 50 mg and 100 mg (1:1 ratio) for 4 weeks after 4 weeks of single-blind sildenafil 50 mg. Exclusion criteria included recent significant cardiovascular disease, use of nitrates, nitric oxide donors, cytochrome P450 3A4 inhibitors, or other erectile dysfunction treatment, and sildenafil hypersensitivity or previous severe or serious treatment-related adverse event. Scores on the QEQ, QEQ Question 5 (satisfaction with erection hardness), the Self-Esteem and Relationship Questionnaire, and the Erectile Dysfunction Inventory of Treatment Satisfaction; the percentage of occasions with Erection Hardness Score 3 (EHS 3, hard enough for penetration but not completely hard) and/or EHS 4 (completely hard and fully rigid); and Pearson correlation coefficients. 1,296 men (18-80 years) were randomized. Except for the percentage of occasions with EHS 3, all outcomes improved in men treated with sildenafil and correlated positively with the change in QEQ scores in all trials. Satisfaction with the quality of erections, which is easily monitored with the QEQ, correlated positively with measures of emotional well-being and treatment satisfaction and with the change in percentage of erections that were completely hard and fully rigid, but not with the change in percentage of erections that were hard enough for penetration but not completely hard.

Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Borgi, Lea; McMullan, Ciaran; Wohlhueter, Ann; Curhan, Gary C; Fisher, Naomi D; Forman, John P

2017-02-01

Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight, or obese individuals with higher serum uric acid (body mass index ≥25 kg/m 2 and serum uric acid ≥5.0 mg/dL), we assigned subjects to probenecid (500-1000 mg/d), allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension. © 2016 American Heart Association, Inc.

Serial evaluation of the MODS, SOFA and LOD scores to predict ICU mortality in mixed critically ill patients.

PubMed

Khwannimit, Bodin

2008-09-01

To perform a serial assessment and compare ability in predicting the intensive care unit (ICU) mortality of the multiple organ dysfunction score (MODS), sequential organ failure assessment (SOFA) and logistic organ dysfunction (LOD) score. The data were collected prospectively on consecutive ICU admissions over a 24-month period at a tertiary referral university hospital. The MODS, SOFA, and LOD scores were calculated on initial and repeated every 24 hrs. Two thousand fifty four patients were enrolled in the present study. The maximum and delta-scores of all the organ dysfunction scores correlated with ICU mortality. The maximum score of all models had better ability for predicting ICU mortality than initial or delta score. The areas under the receiver operating characteristic curve (AUC) for maximum scores was 0.892 for the MODS, 0.907 for the SOFA, and 0.92for the LOD. No statistical difference existed between all maximum scores and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Serial assessment of organ dysfunction during the ICU stay is reliable with ICU mortality. The maximum scores is the best discrimination comparable with APACHE II score in predicting ICU mortality.

The prognostic and risk-stratified value of heart-type fatty acid-binding protein in septic patients in the emergency department.

PubMed

Chen, Yun-Xia; Li, Chun-Sheng

2014-08-01

To evaluate the prognostic and risk-stratified ability of heart-type fatty acid-binding protein (H-FABP) in septic patients in the emergency department (ED). From August to November 2012, 295 consecutive septic patients were enrolled. Circulating H-FABP was measured. The predictive value of H-FABP for 28-day mortality, organ dysfunction on ED arrival, and requirement for mechanical ventilation or a vasopressor within 6 hours after ED arrival was assessed by the receiver operating characteristic curve and logistic regression and was compared with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Mortality in Emergency Department Sepsis (MEDS) score, and Sequential Organ Failure Assessment score. The 28-day mortality, APACHE II, MEDS, and Sequential Organ Failure Assessment scores were much higher in H-FABP-positive patients. The incidence of organ dysfunction at ED arrival and requirement for mechanical ventilation or a vasopressor within 6 hours after ED arrival was higher in H-FABP-positive patients. Heart-type fatty acid-binding protein was an independent predictor of 28-day mortality and organ dysfunction. The area under the receiver operating characteristic curve for H-FABP predicting 28-day mortality and organ dysfunction was 0.784 and 0.755, respectively. Combination of H-FABP and MEDS improved the performance of MEDS in predicting organ dysfunction, and the difference of AUC was statistically significant (P<.05). The combinations of H-FABP and MEDS or H-FABP and APACHE II also improved the prognostic value of MEDS and APACHE II, but the areas under the curve were not statistically different. Heart-type fatty acid-binding protein was helpful for prognosis and risk stratification of septic patients in the ED. Copyright © 2014 Elsevier Inc. All rights reserved.

Targeting NADPH oxidases in vascular pharmacology

PubMed Central

Schramm, Agata; Matusik, Paweł; Osmenda, Grzegorz; Guzik, Tomasz J

2012-01-01

Oxidative stress is a molecular dysregulation in reactive oxygen species (ROS) metabolism, which plays a key role in the pathogenesis of atherosclerosis, vascular inflammation and endothelial dysfunction. It is characterized by a loss of nitric oxide (NO) bioavailability. Large clinical trials such as HOPE and HPS have not shown a clinical benefit of antioxidant vitamin C or vitamin E treatment, putting into question the role of oxidative stress in cardiovascular disease. A change in the understanding of the molecular nature of oxidative stress has been driven by the results of these trials. Oxidative stress is no longer perceived as a simple imbalance between the production and scavenging of ROS, but as a dysfunction of enzymes involved in ROS production. NADPH oxidases are at the center of these events, underlying the dysfunction of other oxidases including eNOS uncoupling, xanthine oxidase and mitochondrial dysfunction. Thus NADPH oxidases are important therapeutic targets. Indeed, HMG-CoA reductase inhibitors (statins) as well as drugs interfering with the renin-angiotensin-aldosterone system inhibit NADPH oxidase activation and expression. Angiotensin-converting enzyme (ACE) inhibitors, AT1 receptor antagonists (sartans) and aliskiren, as well as spironolactone or eplerenone, have been discussed. Molecular aspects of NADPH oxidase regulation must be considered, while thinking about novel pharmacological targeting of this family of enzymes consisting of several homologs Nox1, Nox2, Nox3, Nox4 and Nox5 in humans. In order to properly design trials of antioxidant therapies, we must develop reliable techniques for the assessment of local and systemic oxidative stress. Classical antioxidants could be combined with novel oxidase inhibitors. In this review, we discuss NADPH oxidase inhibitors such as VAS2870, VAS3947, GK-136901, S17834 or plumbagin. Therefore, our efforts must focus on generating small molecular weight inhibitors of NADPH oxidases, allowing the selective inhibition of dysfunctional NADPH oxidase homologs. This appears to be the most reasonable approach, potentially much more efficient than non-selective scavenging of all ROS by the administration of antioxidants. PMID:22405985

Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis

PubMed Central

Lowes, D. A.; Webster, N. R.; Murphy, M. P.; Galley, H. F.

2013-01-01

Background Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage. Methods Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines. Results MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001). Conclusions Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis. PMID:23381720

Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials.

PubMed

Ezekowitz, Justin A; McAlister, Finlay A

2009-02-01

Aldosterone blockade has been used to treat acute myocardial infarction (MI) and chronic heart failure. The aim of this study is to summarize the evidence on the efficacy of spironolactone (SP), eplerenone (EP), or canrenoate (CAN) in patients with left ventricular dysfunction. A search of multiple electronic databases until June 2008 was supplemented by hand searches of reference lists of included studies and review articles, meeting abstracts, FDA reports, and contact with study authors and drug manufacturers. Studies were eligible for inclusion if they included patients with left ventricular systolic or diastolic dysfunction, treatment with SP, EP, or CAN vs. control, and reported clinical outcomes. Nineteen randomized controlled trials (four in acute MI and 15 in heart failure, n = 10 807 patients) were included -- 14 of SP, three of EP, and three of CAN. Analysis was performed using relative risks (RRs) with 95% confidence intervals (CIs) and a random effects model with statistical heterogeneity assessed by I(2). Aldosterone blockade reduced all-cause mortality by 20% (RR 0.80, 95% CI 0.74-0.87). All-cause mortality was reduced in both heart failure (RR = 0.75, 95% CI 0.67-0.84) and post-MI (RR 0.85, 95% CI 0.76-0.95) patients. Only nine trials reported hospitalizations, and the RR reduction was 23% (RR 0.77, 95% CI 0.68-0.87), although 98% of the outcomes came from two trials. Ejection fraction (EF) improved in the seven heart failure trials, which assessed this outcome (weighted mean difference 3.1%, 95% CI 1.6-4.5). We demonstrated a 20% reduction in all-cause mortality with the use of aldosterone blockade in a clinically heterogeneous group of clinical trial participants with heart failure and post-MI. In addition, we found a 3.1% improvement in EF. Further study in those with less severe symptoms or preserved systolic function is warranted.

Maca (L. meyenii) for improving sexual function: a systematic review.

PubMed

Shin, Byung-Cheul; Lee, Myeong Soo; Yang, Eun Jin; Lim, Hyun-Suk; Ernst, Edzard

2010-08-06

Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction. We searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors. Four RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects. The results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted.

Rosa Damascena oil improved sexual function and testosterone in male patients with opium use disorder under methadone maintenance therapy-results from a double-blind, randomized, placebo-controlled clinical trial.

PubMed

Farnia, Vahid; Tatari, Faeze; Alikhani, Mostafa; Shakeri, Jalal; Taghizadeh, Moshen; Karbasizadeh, Hassan; Sadeghi Bahmani, Dena; Holsboer-Trachsler, Edith; Brand, Serge

2017-07-01

Some patients with opioid use disorder (OUD) are treated with methadone maintenance therapy (MMT). However, as with opioids, methadone has major side-effects; sexual dysfunction is a particularly distressing such effect. Rosa Damascena oil has been shown to reduce subjective sexual dysfunction in patients with major depressive disorders, but its influence on testosterone has not so far been tested. The aim of the present study was to investigate the influence of Rosa Damascena oil on sexual dysfunction and testosterone levels among male patients with OUD and undergoing MMT. A total of 50 male patients (mean age: 40 years) diagnosed with OUD and receiving MMT were randomly assigned either to the Rosa Damascena oil (drops) or a placebo condition. At baseline, and four and eight weeks later, patients completed questionnaires covering sexual and erectile function. Blood samples to assess testosterone levels were taken at baseline and eight weeks later on completion of the study. Over time sexual dysfunction decreased, and testosterone increased in the Rosa Damascena oil, but not in the placebo condition. Sexual dysfunction scores and testosterone levels were not consistently related. Results from this double-blind, randomized, and placebo-controlled clinical trial showed that Rosa Damascena oil improved sexual function and testosterone levels among males with OUD and undergoing MMT. Copyright © 2017 Elsevier B.V. All rights reserved.

Trial-unique, delayed nonmatching-to-location (TUNL) touchscreen testing for mice: sensitivity to dorsal hippocampal dysfunction.

PubMed

Kim, Chi Hun; Romberg, Carola; Hvoslef-Eide, Martha; Oomen, Charlotte A; Mar, Adam C; Heath, Christopher J; Berthiaume, Andrée-Anne; Bussey, Timothy J; Saksida, Lisa M

2015-11-01

The hippocampus is implicated in many of the cognitive impairments observed in conditions such as Alzheimer's disease (AD) and schizophrenia (SCZ). Often, mice are the species of choice for models of these diseases and the study of the relationship between brain and behaviour more generally. Thus, automated and efficient hippocampal-sensitive cognitive tests for the mouse are important for developing therapeutic targets for these diseases, and understanding brain-behaviour relationships. One promising option is to adapt the touchscreen-based trial-unique nonmatching-to-location (TUNL) task that has been shown to be sensitive to hippocampal dysfunction in the rat. This study aims to adapt the TUNL task for use in mice and to test for hippocampus-dependency of the task. TUNL training protocols were altered such that C57BL/6 mice were able to acquire the task. Following acquisition, dysfunction of the dorsal hippocampus (dHp) was induced using a fibre-sparing excitotoxin, and the effects of manipulation of several task parameters were examined. Mice could acquire the TUNL task using training optimised for the mouse (experiments 1). TUNL was found to be sensitive to dHp dysfunction in the mouse (experiments 2, 3 and 4). In addition, we observed that performance of dHp dysfunction group was somewhat consistently lower when sample locations were presented in the centre of the screen. This study opens up the possibility of testing both mouse and rat models on this flexible and hippocampus-sensitive touchscreen task.

Sex therapy for female sexual dysfunction

PubMed Central

2013-01-01

Introduction About 45% of women suffer from some form of sexual dysfunction. Despite its high prevalence, there are few studies that have systematically evaluated sex therapy in comparison with other interventions. Objective Review randomized clinical trials that present psychotherapeutic interventions for female sexual dysfunctions. Method Through a search in three databases (Medline, Web of Science and PsycInfo), 1419 references were found. After an analysis of the abstracts, twenty-seven articles met the inclusion criteria and composed this review. Results Sex therapy, as proposed by Masters and Johnson and Heiman and LoPiccolo, is still the most commonly used form of therapy for sexual dysfunctions; although it has shown results, the results do not consistently support that this is the best alternative in the treatment of sexual dysfunctions. Conclusion There is a lack of systematic study of many female sexual dysfunctions. Orgasmic disorder and sexual pain (vaginismus and dyspaurenia) are the most extensively studied disorders and those in which sex therapy seems to have better outcomes. PMID:24066697

The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

PubMed

Eichhorn, Eric J; Bristow, Michael R

2001-01-01

Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of beta-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of beta-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction.

The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial

PubMed Central

Eichhorn, Eric J; Bristow, Michael R

2001-01-01

Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of β-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of β-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction. PMID:11806769

Combining novel technologies with improved logistics to reduce hemodialysis vascular access dysfunction.

PubMed

Roy-Chaudhury, P; Lee, T; Duncan, H; El-Khatib, M

2009-01-01

Hemodialysis (HD) vascular access dysfunction is currently a huge clinical problem for which there are no effective therapies. There are, however, a number of promising technologies that are currently at the experimental or clinical trial stage. We believe that the application of these novel technologies in combination with better clinical protocols for vascular access care could significantly reduce the current problems associated with HD vascular access.

Effectiveness of Phosphodiesterase 5 Inhibitors in the Treatment of Erectile Dysfunction in Patients with Spinal Cord Trauma: Systematic Review and Meta-Analysis.

PubMed

García-Perdomo, Herney Andrés; Echeverría-García, Fernando; Tobías, Aurelio

2017-01-01

To determine the effectiveness of the Phosphodiesterase 5 (PDE5) Inhibitors for the treatment of erectile dysfunction in patients with spinal trauma. A systematic review and meta-analysis comparing PDE5 inhibitors versus placebo were carried out for clinical trials conducted between 1980 and 2014 that evaluated male patients older than 18 years, diagnosed with spinal cord trauma and erectile dysfunction. We designed a search strategy for Medline, CENTRAL, EMBASE and other electronic sources. Two investigators independently and blindly screened the studies for inclusion. A random effect meta-analysis was performed. Six studies involving 963 patients were included. Male patients over 18 years with ED attributable or subsequent to traumatic spinal cord injury (SCI) were included from these studies. In 4 of these studies, patients were randomized to the treatment group receiving sildenafil and the comparison group was placebo. Out of the remaining 2 trials, one compared tadalafil against the placebo and the other vardenafil versus placebo. The improvement on SCIs with PDE5 inhibitors was found to be large (standardized mean difference 0.71; 95% CI 0.39-1.03), with a high heterogeneity (I2 = 74.4%). PDE5 inhibitors are effective for the treatment of erectile dysfunction secondary to SCI. © 2016 S. Karger AG, Basel.

Preconception management of thyroid dysfunction.

PubMed

Okosieme, Onyebuchi E; Khan, Ishrat; Taylor, Peter N

2018-04-29

Uncorrected thyroid dysfunction in pregnancy has well-recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre-empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves' disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy. © 2018 John Wiley & Sons Ltd.

Realizing the promise of personalized medicine.

PubMed

Aspinall, Mara G; Hamermesh, Richard G

2007-10-01

Scientific advances have begun to give doctors the power to customize therapy for individuals. However, adoption of this approach has progressed slowly and unevenly because the trial-and-error treatment model still governs how the health care system develops, regulates, pays for, and delivers therapies. Aspinall, the president of Genzyme Genetics, and Hamermesh, chair of a Harvard Business School initiative to improve leadership in health care organizations, discuss the barriers to personalized medicine and suggest ways to overcome them. The blockbuster model for developing drugs, the authors point out, is still what most major pharmaceutical companies follow, even though its days are numbered. What the industry must embrace in its place is a business model based on a larger portfolio of targeted--and therefore more effective and profitable--treatments, not a limited palette of one-size-fits-all drugs. The current regulatory environment overemphasizes large-scale clinical trials of broad-based therapies. Instead, the focus should be on enrolling subpopulations, based on diagnostic testing, in trials of targeted drug treatments and on monitoring and assessing effectiveness after drugs are approved. A dysfunctional payment system complicates matters by rewarding providers for performance of procedures rather than for accurate diagnosis and effective prevention. Aspinall and Hamermesh call for coordinating regulation and reimbursement so that incentives are provided for the right outcomes. Finally, the authors urge changing physicians' habits through education about genomics, diagnostic testing, and targeted therapies. They say that medical schools and physician organizations must become committed advocates of personalized medicine so that patients and the medical industry can get all the benefits it offers.

Epithelial-Mesenchymal Interactions in Urinary Bladder and Small Intestine and How to Apply Them in Tissue Engineering.

PubMed

Jerman, Urška Dragin; Kreft, Mateja Erdani; Veranič, Peter

2015-12-01

Reciprocal interactions between the epithelium and mesenchyme are essential for the establishment of proper tissue morphology during organogenesis and tissue regeneration as well as for the maintenance of cell differentiation. With this review, we highlight the importance of epithelial-mesenchymal cross talk in healthy tissue and further discuss its significance in engineering functional tissues in vitro. We focus on the urinary bladder and small intestine, organs that are often compromised by disease and are as such in need of research that would advance effective treatment or tissue replacement. To date, the understanding of epithelial-mesenchymal reciprocal interactions has enabled the development of in vitro biomimetic tissue equivalents that have provided many possibilities in treating defective, damaged, or even cancerous tissues. Although research of the past several years has advanced the field of bladder and small intestine tissue engineering, one must be aware of its current limitations in successfully and above all safely introducing tissue-engineered constructs into clinical practice. Special attention is in particular needed when treating cancerous tissues, as initially successful tumor excision and tissue reconstruction may later on result in cancer recurrence due to oncogenic signals originating from an altered stroma. Recent rather poor outcomes in pioneering clinical trials of bladder reconstructions should serve as a reminder that recreating a functional organ to replace a dysfunctional one is an objective far more difficult to reach than initially foreseen. When considering effective tissue engineering approaches for diseased tissues in humans, it is imperative to introduce animal models with dysfunctional or, even more importantly, cancerous organs, which would greatly contribute to predicting possible complications and, hence, reducing risks when translating to the clinic.

Adjunctive treatment with lodenafil carbonate for erectile dysfunction in outpatients with schizophrenia and spectrum: a randomized, double-blind, crossover, placebo-controlled trial.

PubMed

Nunes, Luciana Vargas Alves; Lacaz, Fernando Sargo; Bressan, Rodrigo Affonseca; Nunes, Sandra Odebrecht Vargas Alves; Mari, Jair de Jesus

2013-04-01

INTRODUCTION.: Evidence is accumulating to support the presence of erectile dysfunction in patients with schizophrenia. This dysregulation may be amenable to therapeutic intervention to improve adherence and quality of life of patients who suffer from schizophrenia and schizoaffective disorders. AIM.: We aimed to evaluate the use of adjunctive medication lodenafil for the treatment of erectile dysfunction in outpatients with schizophrenia and spectrum. METHODS.: The design was a randomized, double-blind, crossover, placebo-controlled trial with lodenafil and it was carried at the Schizophrenia Outpatients Program. MAIN OUTCOME MEASURES.: The measures used to assess sexual dysfunction were Arizona Sexual Experiences Scale (ASEX) and International Index of Erectile Function (IIEF). The Positive and Negative Syndrome Scale (PANSS) and the Quality of Life Scale (QLS) were also used. The measures included the levels of prolactin, estradiol, luteinizing hormone, sex hormone-binding globulin, free testosterone, and total testosterone at baseline and end point. Lodenafil and placebo pills were used by the patients for 16 weeks. RESULTS.: Fifty male outpatients fulfilled the criteria and 94% of the participants completed the study. Lodenafil and placebo produced improvement in ASEX, IIEF scale, PANSS, and QLS, and there was no statistical difference between lodenafil and placebo groups in all sexual domains in the results of PANSS and QLS and in the results of hormone levels. CONCLUSION.: These results indicate that both lodenafil and placebo were effective in the treatment of erectile dysfunction for schizophrenia. Placebo effect is very important in patients with schizophrenia and this study showed the importance of discussing sexuality and trying to treat these patients. Further studies designed to test treatments of erectile dysfunction in patients who suffer from schizophrenia are necessary. © 2013 International Society for Sexual Medicine.

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial.

PubMed

Dai, Yuk-Ling; Luk, Ting-Hin; Yiu, Kai-Hang; Wang, Mei; Yip, Pandora M C; Lee, Stephen W L; Li, Sheung-Wai; Tam, Sidney; Fong, Bonnie; Lau, Chu-Pak; Siu, Chung-Wah; Tse, Hung-Fat

2011-06-01

Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 μg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047). In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Balloon dilation of the eustachian tube for dilatory dysfunction: A randomized controlled trial.

PubMed

Poe, Dennis; Anand, Vijay; Dean, Marc; Roberts, William H; Stolovitzky, Jose Pablo; Hoffmann, Karen; Nachlas, Nathan E; Light, Joshua P; Widick, Mark H; Sugrue, John P; Elliott, C Layton; Rosenberg, Seth I; Guillory, Paul; Brown, Neil; Syms, Charles A; Hilton, Christopher W; McElveen, John T; Singh, Ameet; Weiss, Raymond L; Arriaga, Moises A; Leopold, John P

2018-05-01

To assess balloon dilation of the Eustachian tube with Eustachian tube balloon catheter in conjunction with medical management as treatment for Eustachian tube dilatory dysfunction. In this prospective, multicenter, randomized, controlled trial, we assigned, in a 2:1 ratio, patients age 22 years and older with Eustachian tube dilatory dysfunction refractory to medical therapy to undergo balloon dilation of the Eustachian tube with balloon catheter in conjunction with medical management or medical management alone. The primary endpoint was normalization of tympanogram at 6 weeks. Additional endpoints were normalization of Eustachian Tube Dysfunction Questionaire-7 symptom scores, positive Valsalva maneuver, mucosal inflammation, and safety. Primary efficacy results demonstrated superiority of balloon dilation of the Eustachian tube with balloon catheter + medical management compared to medical management alone. Tympanogram normalization at 6-week follow-up was observed in 51.8% (72/139) of investigational patients versus 13.9% (10/72) of controls (P < .0001). Tympanogram normalization in the treatment group was 62.2% after 24 weeks. Normalization of Eustachian Tube Dysfunction Questionaire-7 Symptom scores at 6-week follow-up was observed in 56.2% (77/137) of investigational patients versus 8.5% (6/71) controls (P < .001). The investigational group also demonstrated substantial improvement in both mucosal inflammation and Valsalva maneuver at 6-week follow-up compared to controls. No device- or procedure-related serious adverse events were reported for those who underwent balloon dilation of the Eustachian tube. This study demonstrated superiority of balloon dilation of the Eustachian tube with balloon catheter + medical management compared to medical management alone to treat Eustachian tube dilatory dysfunction in adults. 1b. Laryngoscope, 128:1200-1206, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy.

PubMed

Davies, Andrew N; Thompson, Jo

2015-10-05

This is an updated version of the original Cochrane review on parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (published in Issue 3, 2007). Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition. To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction (specifically radiation-induced xerostomia). For this update, we ran searches of the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 6), MEDLINE, EMBASE, and CINAHL in July 2015. We checked the reference lists of retrieved articles for additional studies, contacted experts in the field for unpublished and ongoing trials, and contacted relevant pharmaceutical companies for unpublished and ongoing trials. The selection criteria for the review were: 1) randomised controlled trials; 2) people suffering from radiation-induced salivary gland dysfunction; 3) people treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measure. The two review authors independently collected data from the full-text version of relevant papers including: 1) citation details; 2) participants; 3) interventions; 4) assessments; 5) outcomes (that is efficacy, tolerability); and 6) quality issues.Due to a lack of appropriate data, we were unable to perform a meta-analysis. In the original review, three studies, including a total of 298 participants, fulfilled the inclusion criteria. All three studies involved the use of pilocarpine hydrochloride. We have included no additional studies in the update of the review; we have excluded eight additional studies.The data suggest that pilocarpine hydrochloride is more effective than placebo and at least as effective as artificial saliva. The response rate was 42% to 51%. The time to response was up to 12 weeks. The overall side effect rate was high, and side effects were the main reason for withdrawal (6% to 15% of participants taking 5 mg three times a day had to withdraw). The side effects were usually the result of generalised parasympathomimetic stimulation (for example sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent. There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation-induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.

Mild Cognitive Dysfunction Does Not Affect Diabetes Mellitus Control in Minority Elderly Adults

PubMed Central

Palta, Priya; Golden, Sherita H.; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S.; Shea, Steven; Manly, Jennifer J.; Luchsinger, Jose A.

2015-01-01

OBJECTIVES To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. DESIGN Prospective cohort study. SETTING A minority cohort in New York City previously recruited for a trial of telemedicine. PARTICIPANTS Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). MEASUREMENTS Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. RESULTS Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. CONCLUSION Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. PMID:25439094

Mild cognitive dysfunction does not affect diabetes mellitus control in minority elderly adults.

PubMed

Palta, Priya; Golden, Sherita H; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S; Shea, Steven; Manly, Jennifer J; Luchsinger, Jose A

2014-12-01

To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. Prospective cohort study. A minority cohort in New York City previously recruited for a trial of telemedicine. Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Cardiovascular alterations and multi organ dysfunction after birth asphyxia

PubMed Central

Polglase, Graeme R.; Ong, Tracey; Hillman, Noah H

2016-01-01

Synopsis The cardiovascular response to asphyxia involves redistribution of cardiac output to maintain oxygen delivery to critical organs such as the adrenal gland, heart and brain, at the expense of other organs such as the gut, kidneys and skin. This results in reduced perfusion and localized hypoxia/ischemia in these organs, which if severe, can result in multi-organ failure. Liver injury, coagulopathy, bleeding, thrombocytopenia, renal dysfunction, pulmonary and gastrointestinal injury all result from hypoxia, under-perfusion or both. Current clinical therapies need to be considered together with therapeutic hypothermia and cardiovascular recovery. PMID:27524448

Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials.

PubMed

Bernardi, Mauro; Caraceni, Paolo; Navickis, Roberta J; Wilkes, Mahlon M

2012-04-01

Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites, as compared with no treatment. Treatment alternatives to albumin, such as artificial colloids and vasoconstrictors, have been widely investigated. The aim of this meta-analysis was to determine whether morbidity and mortality differ between patients receiving albumin versus alternative treatments. The meta-analysis included randomized trials evaluating albumin infusion in patients with tense ascites. Primary endpoints were postparacentesis circulatory dysfunction, hyponatremia, and mortality. Eligible trials were sought by multiple methods, including computer searches of bibliographic and abstract databases and the Cochrane Library. Results were quantitatively combined under a fixed-effects model. Seventeen trials with 1,225 total patients were included. There was no evidence of heterogeneity or publication bias. Compared with alternative treatments, albumin reduced the incidence of postparacentesis circulatory dysfunction (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.27-0.55). Significant reductions in that complication by albumin were also shown in subgroup analyses versus each of the other volume expanders tested (e.g., dextran, gelatin, hydroxyethyl starch, and hypertonic saline). The occurrence of hyponatremia was also decreased by albumin, compared with alternative treatments (OR, 0.58; 95% CI, 0.39-0.87). In addition, mortality was lower in patients receiving albumin than alternative treatments (OR, 0.64; 95% CI, 0.41-0.98). This meta-analysis provides evidence that albumin reduces morbidity and mortality among patients with tense ascites undergoing large-volume paracentesis, as compared with alternative treatments investigated thus far. Copyright © 2011 American Association for the Study of Liver Diseases.

Risk Factors for Sexual Dysfunction Among Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015.

PubMed

McCabe, Marita P; Sharlip, Ira D; Lewis, Ron; Atalla, Elham; Balon, Richard; Fisher, Alessandra D; Laumann, Edward; Lee, Sun Won; Segraves, Robert T

2016-02-01

This article presents a review of previous research concerning risk factors for sexual dysfunction in women and men. The aim is to evaluate past research studies to determine the contribution of all risk factors to the development and maintenance of sexual dysfunction among women and men. Studies were organized under a biopsychosocial framework, with the bulk of studies of women and men having investigated the role of biological factors. The outcome measures were the data on factors for sexual dysfunction. Many more studies investigated risk factors for sexual dysfunction in men than in women. For women and men, diabetes, heart disease, urinary tract disorders, and chronic illness were significant risk factors for sexual dysfunction. Depression and anxiety and the medications used to treat these disorders also were risk factors for sexual dysfunction in women and men. In addition, substance abuse was associated with sexual dysfunction. Many other social and cultural factors were related to sexual dysfunction in women and men. Psychosocial factors are clearly risk factors for sexual dysfunction. Women and men with sexual dysfunction should be offered psychosocial evaluation and treatment, if available, in addition to medical evaluation and treatment. The impact of social and cultural factors on sexual function requires substantially more research. The evidence that erectile dysfunction is a harbinger of other forms of cardiovascular disease is strong enough to recommend that clinical evaluation for occult cardiovascular disease should be undertaken in men who do not have known cardiovascular disease but who develop organic erectile dysfunction, especially in men younger than 70 years. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Legacy Clinical Data from the Epo TBI Trial

DTIC Science & Technology

2016-06-01

investigators through the Federal Interagency Traumatic Brain Injury (FITBIR) Informatics System. This trial was funded by National Institute of Neurological...Effects of Erythropoietin (Epo) on Cerebral Vascular Dysfunction and Anemia in Traumatic Brain Injury (TBI)” which we will share with other...the format required by FITBIR. 2. KEYWORDS: Traumatic brain injury Erythropoietin Anemia Transfusion threshold 3. ACCOMPLISHMENTS: What

Dimensions of dependence and their influence on the outcome of cognitive behaviour therapy for health anxiety: randomized controlled trial.

PubMed

Tyrer, Peter; Wang, Duolao; Tyrer, Helen; Crawford, Mike; Cooper, Sylvia

2016-05-01

The personality trait of dependence is common in health-seeking behaviour. We therefore examined its impact in a large randomized controlled trial of psychological treatment for health anxiety. To test whether dependent personality traits were positive or negative in determining the outcome of an adapted form of cognitive behaviour therapy for health anxiety (CBT-HA) over the course of 5 years and whether dependent personality dysfunction could be viewed dimensionally in a similar way to the new ICD-11 diagnostic system for general personality disorder. Dependent personality dysfunction was assessed using a self-rated questionnaire, the Dependent Personality Questionnaire, at baseline in a randomized controlled trial of 444 patients from medical clinics with pathological health anxiety treated with a modified form of CBT-HA or standard treatment in the medical clinics, with assessment on five occasions over 5 years. Dependent personality dysfunction was assessed using four severity groups. Patients with mild and moderate dependent personality disorder treated with CBT-HA showed the greatest reduction in health anxiety compared with standard care, and those with no dependent dysfunction showed the least benefit. Patients with higher dependent traits received significantly more treatment sessions (8.6) than those with low trait levels (5.4) (p < 0.01). The results suggest that patients treated with cognitive behaviour therapy for health anxiety respond better if they have moderate dependent personality. The reasons for this may be related to better adherence to psychological treatment and greater negative effects of frequent reassurance and excessive consultation in those treated in standard care. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and human studies

PubMed Central

Lewis, Alan S.; van Schalkwyk, Gerrit I.; Bloch, Michael H.

2017-01-01

Cognitive dysfunction in schizophrenia (SCZ) and Alzheimer’s disease (AD) is a major driver of functional disability but is largely unresponsive to current therapeutics. Animal models of cognitive dysfunction relevant to both disorders suggest the α7 nicotinic acetylcholine receptor (nAChR) may be a promising drug development target, with multiple clinical trials subsequently testing this hypothesis in individuals with SCZ and AD. However, the translational value of rodent cognitive tasks for predicting the overall efficacy of this therapeutic target in clinical trials is unknown. To compare effect sizes between rodent and human studies, we searched PubMed and the Cochrane Library for all randomized, placebo-controlled trials of compounds with pharmacological activity at the α7 nAChR for treatment of cognitive dysfunction in SCZ and AD and identified 18 studies comprising 2670 subjects treated with eight different compounds acting as full or partial agonists. Cognitive outcomes were standardized, and random-effects meta-analyses revealed no statistically significant effects of α7 nAChR agonists on overall cognition or any of eight cognitive subdomains when all doses were included (Range of all cognitive outcomes: Cohen’s d = −0.077 to 0.12, negative favoring drug). In contrast, analysis of 29 rodent studies testing the same α7 agonists revealed large effect sizes in multiple commonly used preclinical behavioral tests of cognition (Range: d = −1.18 to −0.73). Our results suggest that targeting the α7 nAChR with agonists is not a robust treatment for cognitive dysfunction in SCZ or AD and necessitate a better understanding of the translational gap for therapeutics targeting the α7 nAChR. PMID:28065843

Immune-directed therapy for type 1 diabetes at the clinical level: the Immune Tolerance Network (ITN) experience.

PubMed

Ehlers, Mario R; Nepom, Gerald T

2012-01-01

Reestablishing immune tolerance in type 1 diabetes (T1D), a chronic autoimmune disease, is a major goal. The Immune Tolerance Network (ITN) has initiated eight clinical trials of immunomodulatory therapies in recent-onset T1D over the past decade. Results have been mixed in terms of clinical efficacy, but the studies have provided valuable mechanistic insight that are enhancing our understanding of the disease and guiding the design of future trials. Trials of non-Fc-binding anti-CD3 mAbs have revealed that modulation of this target leads to partial responses, and ITN's AbATE trial led to identification of a robust responder group that could be distinguished from non-responders by baseline metabolic and immunologic features. A pilot study of the combination of IL-2 and rapamycin gave the first demonstration that frequency and function of regulatory T cells (Tregs) can be enhanced in T1D subjects, although the therapy triggered the activation of effectors with transient β-cell dysfunction. Similarly, therapy with anti-thymocyte globulin led to substantial lymphocyte depletion, but also to the activation of the acute-phase response with no clinical benefit during preliminary analyses. These and other results provide mechanistic tools that can be used as biomarkers for safety and efficacy in future trials. Furthermore, our results, together with those of other organizations, notably TrialNet, delineate the roles of the major components of the immune response in T1D. This information is setting the stage for future combination therapy trials. The development of disease-relevant biomarkers will also enable the implementation of innovative trial designs, notably adaptive trials, which will increase efficiencies in terms of study duration and sample size, and which will expedite the conduct of trials in which there are uncertainties about dose response and effect size.

Ambulatory blood pressure monitoring in solid organ transplantation.

PubMed

Ramesh Prasad, G V

2012-01-01

Solid organ transplant recipients are at an increased risk for hypertension and cardiovascular disease. To assist in their management, 24-h ambulatory blood pressure monitoring (ABPM) has become increasingly used in both clinical research settings and practice. ABPM has been used to better define post-transplant hypertension incidence and prevalence in different solid organ transplantation populations. ABPM provides additional information on cardiovascular risk beyond that obtained by clinic-based readings, based on its ability to assess 24-h blood pressure (BP) load, detect nocturnal non-dipping, and predict target organ damage. It has provided some assurance about the safety of living kidney donation. Information from ABPM can be used to guide living kidney donor selection, and because ABPM-related data has been correlated with clinically important kidney and heart transplant recipient outcomes, it may be a valuable adjunct in their management. Despite these advantages, barriers to wider use of ABPM include expense, clinical inertia in hypertension management, lack of prospective clinical trial data, and clinical problems that compete with hypertension for attention such as acute or chronic allograft dysfunction. The increasing amount of research and clinical use for ABPM may allow for closer assessment and intervention to help address the increased cardiovascular risk faced by many solid organ transplant recipients. © 2011 John Wiley & Sons A/S.

Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction: A subgroup analysis of the PROTECT trial

PubMed Central

Adhikari, Neill K. J.; Ostermann, Marlies; Heels-Ansdell, Diane; Douketis, James D.; Skrobik, Yoanna; Qushmaq, Ismael; Meade, Maureen; Guyatt, Gordon; Geerts, William; Walsh, Michael W.; Crowther, Mark A.; Friedrich, Jan O.; Burry, Lisa; Bellomo, Rinaldo; Brandão da Silva, Nilton; Costa Filho, Rubens; Cox, Michael J.; Alves Silva, Suzana; Cook, Deborah J.

2018-01-01

Introduction There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial. Methods We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance [CrCl] <30 ml/min; post hoc subgroup; n = 590). We compared dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios [HR] were calculated using Cox regression. Results In patients with ESRD, there was no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and dalteparin. In patients with severe renal dysfunction, there was no significant difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were non-significant. Conclusions In critically ill patients with ESRD, or severe renal dysfunction, there was no significant difference in any VTE or major bleeding between UFH and dalteparin. Patients with severe renal dysfunction who received dalteparin had more proximal DVTs than those on UFH; this finding did not hold in patients with ESRD alone. PMID:29856817

Self-reported impulsivity in Huntington's disease patients and relationship to executive dysfunction and reward responsiveness.

PubMed

Johnson, Patricia L; Potts, Geoffrey F; Sanchez-Ramos, Juan; Cimino, Cynthia R

2017-09-01

Few studies have directly investigated impulsivity in Huntington's disease (HD) despite known changes in dopaminergic and frontal functioning, changes that have been associated with impulsivity in other disorders and in the normal population. This study sought to further categorize impulsivity in HD through examining differences in self-reported impulsivity between community controls and HD patients, the relationship between executive dysfunction and impulsivity, and the relationship of a reward/punishment behavioral inhibition task in relation to these self-report measures. It was expected that HD patients would report higher impulsivity and executive dysfunction and that these measures would relate to a reward/punishment behavioral inhibition task. The Barratt Impulsivity Scale (BIS-11) and Behavioral Inhibition/Behavioral Activation Scale (BIS/BAS) were completed, and the Mini-Mental State Examination (MMSE) and a reward-based flanker task with punishing and rewarding conditions were administered to 22 HD patients and 14 control participants. HD patients reported higher trait impulsivity (BIS-11) and executive dysfunction (Frontal Systems Behavior Scale, FrSBE) but not increased impulsivity on the BIS/BAS relative to controls. Higher BIS-11 scores were related to increased self-reported executive dysfunction and the attention/working memory factor of the MMSE. On a reward/punishment behavioral inhibition task, BAS was uniquely related to increased accuracy on rewarding trials of the flanker task, but was not related to punishing trials in HD patients. The relationships found suggest that trait impulsivity is reported higher in HD and may not be driven by altered reward evaluation and the appetitive nature of stimuli but rather by increased executive dysfunction and lack of sensitivity to punishment. Impulsivity in HD may represent a combination of trait impulsivity, altered dopaminergic circuitry, and executive dysfunction. Understanding impulsivity in HD is important as it is related to increased risk to the patient and difficult behaviors for the caregiver, and sheds light on the disease process.

Flavanol-rich cocoa ameliorates lipemia-induced endothelial dysfunction.

PubMed

Westphal, Sabine; Luley, Claus

2011-09-01

Consumption of flavanols improves chronic endothelial dysfunction. We investigated whether it can also improve acute lipemia-induced endothelial dysfunction. In this randomized, placebo-controlled, double-blind, crossover trial, 18 healthy subjects received a fatty meal with cocoa either rich in flavanols (918 mg) or flavanol-poor. Flow-mediated dilation (FMD), triglycerides, and free fatty acids were then determined over 6 h. After the flavanol-poor fat loading, the FMD deteriorated over 4 h. The consumption of flavanol-rich cocoa, in contrast, improved this deterioration in hours 2, 3, and 4 without abolishing it completely. Flavanols did not have any influence on triglycerides or on free fatty acids. Flavanol-rich cocoa can alleviate the lipemia-induced endothelial dysfunction, probably through an improvement in endothelial NO synthase.

Amiodarone therapy in chronic heart failure and myocardial infarction: a review of the mortality trials with special attention to STAT-CHF and the GESICA trials. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina.

PubMed

Pinto, J V; Ramani, K; Neelagaru, S; Kown, M; Gheorghiade, M

1997-01-01

Amiodarone appears to reduce sudden death in patients with left ventricular dysfunction resulting from an acute MI or a primary dilated cardiomyopathy, particularly if complex ventricular arrhythmias are present. Amiodarone's beneficial effect on mortality in these patients could be unrelated to its antiarrhythmic effects. Multiple factors could account for the improvement in mortality such as the drug's antiischemic effects, neuromodulating effects, its effect on left ventricular function and on heart rate. Moreover, patients with LV dysfunction who have survived an episode of sudden death would potentially benefit from amiodarone therapy. Future trials are needed to determine the precise subsets(s) of patients who would benefit from the drug and the most efficacious dosing regimen for the drug. Based on available data, amiodarone is the only antiarrhythmic agent which has not been shown to increase mortality in patients with chronic heart failure.

Feasibility study of cytokine removal by hemoadsorption in brain-dead humans.

PubMed

Kellum, John A; Venkataraman, Ramesh; Powner, David; Elder, Michele; Hergenroeder, Georgene; Carter, Melinda

2008-01-01

Inflammatory cytokines occur in the circulation and in the tissues after brain death and have been associated with dysfunction of donor organs before and after transplantation. To determine the feasibility of removing cytokines using a hemoadsorption device. Two-center, randomized, open-label, feasibility study in which brain-dead subjects were randomized to two treatment groups. Two U.S. academic hospitals. Eight brain-dead subjects deemed unsuitable for organ donation by respective organ procurement organizations. After obtaining consent from families, subjects were treated with hemoadsorption for 4 hrs using CytoSorb. Effects on cytokines (tumor necrosis factor, interleukin [IL]-6, and IL-10) were assessed both across the device and in the plasma over time. Feasibility for cytokine removal was assessed using objective criteria. Cytokine removal across the CytoSorb device ranged from 4% to 30% and was not significantly different from 1 hr to 4 hrs. Overall removal was greatest for IL-6, 28% (p = .006), and least for tumor necrosis factor, 8.5% (p = .13). Plasma concentrations of both IL-6 and tumor necrosis factor, but not IL-10, were significantly reduced after the first hour of therapy; mean differences were -13% +/- 7% for IL-6 (p = .039), -23% +/- 9% for tumor necrosis factor (p = .02), and -2% +/- 7% of IL-10 (p = 23). However, plasma concentrations for all three cytokines increased over time and were above baseline by the end of the intervention. No adverse effects of therapy were observed. However, removal of cortisol and triiodothyronine was similar to removal of cytokines. Hemoadsorption for removal of cytokines in brain-dead subjects is feasible. Evaluation of possible clinical benefit will require controlled trials in actual donors. However, the significant capacity for cytokine removal and absence of adverse events suggest that such trials are warranted.

Long term verbal memory recall deficits in fragile X premutation females.

PubMed

Shelton, Annie L; Cornish, Kim; Fielding, Joanne

2017-10-01

Carriers of a FMR1 premutation allele (between 55 and 199 CGG repeats) are at risk of developing a wide range of medical, psychiatric and cognitive disorders, including executive dysfunction. These cognitive deficits are often less severe for female premutation carriers compared to male premutation carriers, albeit similar in nature. However, it remains unclear whether female premutation carriers who exhibit executive dysfunction also report verbal learning and memory deficits like those of their male counterparts. Here we employed the CVLT to assess verbal learning and memory function in 19 female premutation carriers, contrasting performance with 19 age- and IQ-matched controls. Group comparisons revealed similar performance during the learning and short delay recall phases of the CVLT. However, after a long delay period, female premutation carriers remembered fewer words for both free and cued recall trials, but not during recognition trials. These findings are consistent with reports for male premutation carriers, and suggest that aspects of long term memory may be adversely affect in a subgroup of premutation carriers with signs of executive dysfunction. Copyright © 2017. Published by Elsevier Inc.

Colloids Versus Albumin in Large Volume Paracentesis to Prevent Circulatory Dysfunction: Evidence-based Case Report.

PubMed

Widjaja, Felix F; Khairan, Paramita; Kamelia, Telly; Hasan, Irsan

2016-04-01

Large volume paracentesis may cause paracentesis induced circulatory dysfunction (PICD). Albumin is recommended to prevent this abnormality. Meanwhile, the price of albumin is too expensive and there should be another alternative that may prevent PICD. This report aimed to compare albumin to colloids in preventing PICD. Search strategy was done using PubMed, Scopus, Proquest, dan Academic Health Complete from EBSCO with keywords of "ascites", "albumin", "colloid", "dextran", "hydroxyethyl starch", "gelatin", and "paracentesis induced circulatory dysfunction". Articles was limited to randomized clinical trial and meta-analysis with clinical question of "In hepatic cirrhotic patient undergone large volume paracentesis, whether colloids were similar to albumin to prevent PICD". We found one meta-analysis and four randomized clinical trials (RCT). A meta analysis showed that albumin was still superior of which odds ratio 0.34 (0.23-0.51). Three RCTs showed the same results and one RCT showed albumin was not superior than colloids. We conclude that colloids could not constitute albumin to prevent PICD, but colloids still have a role in patient who undergone paracentesis less than five liters.

The Impact of 5α-Reductase Inhibitor Use for Male Pattern Hair Loss on Men's Health.

PubMed

Said, Mohammed A; Mehta, Akanksha

2018-06-16

Male pattern hair loss, mediated by dihydrotestosterone, is a common hair loss disorder, affecting over 50% of men over the age of 50. The 5-α reductase inhibitors, finasteride and dutasteride, are Food and Drug Administration-approved drugs for the treatment of this disorder. Several recent studies have reported adverse sexual and spermatogenic events among young men using 5-α reductase inhibitors, such as erectile dysfunction, decreased ejaculate volume, decreased libido, and infertility. In this review, we summarize and analyze the literature regarding the efficacy and safety of these medications, with an overall focus on men's health. Finasteride for the treatment of male pattern hair loss was considered safe according to many previous clinical trials. However, these trials have been recently criticized for inadequate safety reporting. Comprehensive review of the current literature reveals that there is a disproportionately high number of men with 5-α reductase inhibitor-associated sexual dysfunction and infertility. Although uncommon, the use of 5-α reductase inhibitors is associated with serious and persistent sexual and reproductive side effects, such as erectile dysfunction, decreased ejaculate volume, decreased libido, and infertility.

Targeting Extracellular Histones with Novel RNA Biodrugs for the Treatment of Acute Lung Injury

DTIC Science & Technology

2017-10-01

inactivate) circulating histones and prevent the morbidity and mortality associated with multiple organ dysfunction/ acute respiratory distress syndrome ...patients. 15. SUBJECT TERMS Acute lung injury (ALI), acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome , extracellular...are acute lung injury (ALI) from smoke/chlorine gas inhalation, burns, radiation , influenza and severe infection. Only recently have investigators

Hypnotic Relaxation Therapy and Sexual Function in PostmenopausalWomen: Results of a Randomized Clinical Trial.

PubMed

Johnson, Aimee K; Johnson, Alisa J; Barton, Debra; Elkins, Gary

2016-01-01

Sexual dysfunction is a common problem for postmenopausal women. This study, as part of a larger randomized controlled trial, examined the effect of hypnotic relaxation therapy on sexual dysfunction, a secondary study outcome, in postmenopausal women. Sexual function was assessed using the Sexual Activity Questionnaire (SAQ). Significant improvement in sexual pleasure and discomfort were reported following 5 weekly sessions of hypnotic relaxation therapy, compared with those receiving an attention control. Total SAQ scores showed significant improvement in the hypnotic relaxation therapy treatment group while holding baseline SAQ scores constant. Improvements showed a slight increase at the Week 12 follow-up. The results of this analysis provide initial support for the use of hypnotic relaxation therapy to improve sexual function in postmenopausal women.

Beneficial effects of dexmedetomidine on early postoperative cognitive dysfunction in pediatric patients with tonsillectomy.

PubMed

Han, Chuanlai; Fu, Rong; Lei, Weifu

2018-07-01

According to clinical investigations, early postoperative cognitive dysfunction is the most common adverse event in pediatric patients after tonsillectomy. A previous study has indicated that dexmedetomidine (DEX) is an efficient drug for the treatment of postoperative cognitive dysfunction. However, the efficacy of DEX in alleviating early postoperative cognitive dysfunction in pediatric patients following tonsillectomy has remained elusive, which was therefore assessed in the present study. A total of 186 children presenting with cognitive dysfunction subsequent to tonsillectomy were recruited to analyze the efficacy of DEX. Patients were randomly divided into two groups and received intravenous treatment with DEX (n=112) or placebo (n=74). Duration of treatment, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of DEX were evaluated in a preliminary experiment. The improvement of postoperative cognitive function in children with tonsillectomy was analyzed with a Mini-Mental State Examination (MMSE) following treatment with DEX. A 40-item quality of life (MONEX-40) questionnaire was used to assess the efficacy of DEX. The plasma levels of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, superoxide dismutase (SOD), neuron-specific enolase (NSE), C-reactive protein (CRP), cortisol and melatonin were also analyzed. The preliminary experiment determined that the DLT was 10 mg/kg and the MTD was 15 mg/kg. In the major clinical trial, it was revealed that MMSE scores in the DEX treatment group were markedly improved, indicating that DEX had a beneficial effect in pediatric patients with early postoperative cognitive dysfunction after tonsillectomy. In addition, IL-1and TNF-α were downregulated, while IL-6 and SOD were upregulated in patients with cognitive dysfunction after treatment with DEX compared with those in the placebo group. Furthermore, DEX treatment markedly decreased the serum levels of CRP, NSE cortisol and melatonin, which are associated with the occurrence of postoperative cognitive dysfunction in pediatric patients following tonsillectomy. In conclusion, intravenous administration of DEX at a dose of 10 mg/kg improves postoperative cognitive function in pediatric patients with tonsillectomy by decreasing the serum levels of inflammatory factors and stress-associated signaling molecules. Trial registration no. QLSDHOS0200810102C (Qilu Hospital of Shandong University, Jinan, China).

Angiogenic factors and their soluble receptors predict organ dysfunction and mortality in post-cardiac arrest syndrome.

PubMed

Wada, Takeshi; Jesmin, Subrina; Gando, Satoshi; Yanagida, Yuichiro; Mizugaki, Asumi; Sultana, Sayeeda N; Zaedi, Sohel; Yokota, Hiroyuki

2012-09-29

Post-cardiac arrest syndrome (PCAS) often leads to multiple organ dysfunction syndrome (MODS) with a poor prognosis. Endothelial and leukocyte activation after whole-body ischemia/reperfusion following resuscitation from cardiac arrest is a critical step in endothelial injury and related organ damage. Angiogenic factors, including vascular endothelial growth factor (VEGF) and angiopoietin (Ang), and their receptors play crucial roles in endothelial growth, survival signals, pathological angiogenesis and microvascular permeability. The aim of this study was to confirm the efficacy of angiogenic factors and their soluble receptors in predicting organ dysfunction and mortality in patients with PCAS. A total of 52 resuscitated patients were divided into two subgroups: 23 survivors and 29 non-survivors. The serum levels of VEGF, soluble VEGF receptor (sVEGFR)1, sVEGFR2, Ang1, Ang2 and soluble Tie2 (sTie2) were measured at the time of admission (Day 1) and on Day 3 and Day 5. The ratio of Ang2 to Ang1 (Ang2/Ang1) was also calculated. This study compared the levels of angiogenic factors and their soluble receptors between survivors and non-survivors, and evaluated the predictive value of these factors for organ dysfunction and 28-day mortality. The non-survivors demonstrated more severe degrees of organ dysfunction and a higher prevalence of MODS. Non-survivors showed significant increases in the Ang2 levels and the Ang2/Ang1 ratios compared to survivors. A stepwise logistic regression analysis demonstrated that the Ang2 levels or the Ang2/Ang1 ratios on Day 1 independently predicted the 28-day mortality. The receiver operating characteristic curves of the Ang2 levels, and the Ang2/Ang1 ratios on Day 1 were good predictors of 28-day mortality. The Ang2 levels also independently predicted increases in the Sequential Organ Failure Assessment (SOFA) scores. We observed a marked imbalance between Ang1 and Ang2 in favor of Ang2 in PCAS patients, and the effect was more prominent in non-survivors. Angiogenic factors and their soluble receptors, particularly Ang2 and Ang2/Ang1, are considered to be valuable predictive biomarkers in the development of organ dysfunction and poor outcomes in PCAS patients.

Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial.

PubMed

Maiden, Matthew J; Chapman, Marianne J; Torpy, David J; Kuchel, Timothy R; Clarke, Iain J; Nash, Coralie H; Fraser, Jonathan D; Ludbrook, Guy L

2016-06-01

Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. Randomized blinded placebo-controlled trial. Preclinical research laboratory. Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

APCAP--activated protein C in acute pancreatitis: a double-blind randomized human pilot trial.

PubMed

Pettilä, Ville; Kyhälä, Lea; Kylänpää, Marja-Leena; Leppäniemi, Ari; Tallgren, Minna; Markkola, Antti; Puolakkainen, Pauli; Repo, Heikki; Kemppainen, Esko

2010-01-01

Previous human studies have shown low activity of protein C (APC) in severe acute pancreatitis (SAP). This, together with the findings in animal models, suggests that activated protein C (APC) may protect against pancreatic injury and ameliorate the disease. We, therefore, evaluated its effect on multiple organ dysfunction (MOD) measured by the SOFA (Sequential Organ Failure Assessment) and on organ-failure-free days, and the safety of APC in SAP. A prospective double blind randomized pilot study was use. The study occurred in one university hospital tertiary intensive care unit (ICU) with eight beds. The patients were chosen according to the following inclusion criteria: 1) Those admitted to the hospital < 96 h from the onset of pain, 2) Those who had a three-fold increase in serum amylase over normal upper range or/and in whom computed tomography (CT) verification of SAP was noted, 3) Those who had one or more organ dysfunction (OD), and 4) Those in whom less than 48 hours had passed since their first OD. Of a total of 215 adult patients with SAP screened between June 2003 and August 2007, 158 fulfilled the study inclusion criteria. After exclusions 32 patients were randomized to the study. The intervention consisted of APC (N = 16) administered intravenously for 96 hours with a dose of 24 μg/kg/hour or placebo (N = 16) with a similar infusion rate. The sample size for the study was calculated according to the primary end-point: the change in SOFA during study drug infusion (Days 0 and 5). Comparisons between the study groups were performed using patient-related changes and calculation of difference in means (DIM, 95% CIs) and regarding categorical variables with Fisher's exact test. For all comparisons P < 0.05 was considered significant. No serious bleeding was detected clinically or by CT scans in either group. No significant difference in SOFA score change between the APC and placebo groups was found (difference in means (DIM) +2.3, 95% CI -0.7 to +5.3). Treatment with APC was associated with an increase in serum levels of both total and conjugated bilirubin. No differences in ventilator-free days, in renal replacement therapy-free days, in vasopressor-free days, or in days alive outside the hospital were detected. No serious bleeding or differences in the evolution of MOD were detected between APC and the placebo. Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP. ClinicalTrials.gov NCT01017107.

In Silico Modeling: Methods and Applications toTrauma and Sepsis

PubMed Central

Vodovotz, Yoram; Billiar, Timothy R.

2013-01-01

Objective To familiarize clinicians with advances in computational disease modeling applied to trauma and sepsis. Data Sources PubMed search and review of relevant medical literature. Summary Definitions, key methods, and applications of computational modeling to trauma and sepsis are reviewed. Conclusions Computational modeling of inflammation and organ dysfunction at the cellular, organ, whole-organism, and population levels has suggested a positive feedback cycle of inflammation → damage → inflammation that manifests via organ-specific inflammatory switching networks. This structure may manifest as multi-compartment “tipping points” that drive multiple organ dysfunction. This process may be amenable to rational inflammation reprogramming. PMID:23863232

Potential beneficial effects of sacubitril-valsartan in renal disease: a new field for a new drug.

PubMed

Gervasini, Guillermo; Robles, Nicolas Roberto

2017-05-01

Patients with renal dysfunction are at a higher risk of cardiovascular disease (CVD), which often shares manifestations with heart failure (HF). Last year, the FDA approved the use of sacubitril-valsartan in patients with HF. This dual-acting agent enhances the functions of natriuretic peptides and inhibits the renin-angiotensin system. Areas covered: This review summarizes the existing preclinical and clinical studies carried out with sacubitril-valsartan (and other drugs with similar pharmacological mechanisms) in HF and hypertensive patients. We put the focus on the renal data provided by these studies. Data were obtained from English peer-reviewed articles on PubMed and clinical trials registered in ClinicalTrials.gov. Expert opinion: Overall, sacubitril-valsartan might be a promising therapeutic approach in patients with renal dysfunction. Renal conditions with marked CV risk, such as arterionephrosclerosis, could constitute a particular setting where to evaluate the impact of the drug. Nevertheless, large, randomized trials are needed to confirm the beneficial effects and safety profile of the drug in renal patients, as well as to elucidate some concerns observed in HF trials, such as the slight increase in proteinuria.

Maca (L. meyenii) for improving sexual function: a systematic review

PubMed Central

2010-01-01

Background Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction. Methods We searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors. Results Four RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects. Conclusion The results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted. PMID:20691074

The roles and potential therapeutic implications of CXCL4 and its variant CXCL4L1 in the pathogenesis of chronic liver allograft dysfunction.

PubMed

Li, Jing; Liu, Bin; Yan, Lu-nan; Lau, Wan-yee

2015-02-01

Chronic liver allograft dysfunction is the leading cause of patient morbidity and late allograft loss after liver transplantation. The pathogenesis of chronic liver allograft dysfunction remains unknown. Recent studies have demonstrated that CXCL4 and its variant CXCL4L1 are involved in organ damage induced through inflammatory and immune responses throughout all stages of liver transplantation. CXCL4 and CXCL4L1 are low-molecular-weight proteins that have been implicated in hematopoiesis, angiostasis, organ fibrogenesis, mitogenesis, tumor growth and metastasis. The purpose of this review is to discuss the current status and future developments of research into the roles of CXCL4 and CXCL4L1 in the pathogenesis of chronic liver allograft dysfunction. The potential utilization of CXCL4 and CXCL4L1 as therapeutic targets for chronic liver allograft dysfunction will also be discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sexual dysfunction during treatment of major depressive disorder with vilazodone, citalopram, or placebo: results from a phase IV clinical trial.

PubMed

Clayton, Anita H; Gommoll, Carl; Chen, Dalei; Nunez, Rene; Mathews, Maju

2015-07-01

Sexual dysfunction commonly occurs with major depressive disorder (MDD). Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist antidepressant approved for the treatment of MDD in adults, was evaluated to determine its effects on sexual function. The primary study was a double-blind, randomized, controlled trial comparing vilazodone 20 and 40 mg/day with placebo; citalopram 40 mg/day was an active control (NCT01473381; http://www.clinicaltrials.gov). Post-hoc analyses evaluated change from baseline to week 10 on the Changes in Sexual Functioning Questionnaire (CSFQ); no inferential statistics were performed. CSFQ scores increased for women [1.2 (citalopram) to 3.0 (vilazodone 40 mg)] and men [1.2 (vilazodone 40 mg) to 3.5 (placebo)] in all treatment groups. Greater changes in CSFQ scores were seen in responders [women: 2.33 (citalopram) to 5.06 (vilazodone 40 mg); men: 2.26 (vilazodone 40 mg) to 4.35 (placebo)] versus nonresponders. CSFQ change from baseline was small for patients with normal baseline sexual function; in patients with baseline sexual dysfunction, CSFQ scores improved across groups [women: 2.35 (citalopram) to 4.52 (vilazodone 40 mg); men 2.83 (vilazodone 40 mg) to 6.43 (placebo)]. Across treatment groups, baseline sexual function improved in women and men, MDD responders, and patients with baseline sexual dysfunction.

Randomised trial comparing hysterectomy with endometrial ablation for dysfunctional uterine bleeding: psychiatric and psychosocial aspects.

PubMed Central

Alexander, D. A.; Naji, A. A.; Pinion, S. B.; Mollison, J.; Kitchener, H. C.; Parkin, D. E.; Abramovich, D. R.; Russell, I. T.

1996-01-01

OBJECTIVE: To compare in psychiatric and psychosocial terms the outcome of hysterectomy and endometrial ablation for the treatment of dysfunctional uterine bleeding. DESIGN: Prospective randomised controlled trial. SETTING--Obstetrics and gynaecology department of a large teaching hospital. SUBJECTS: 204 women with dysfunctional bleeding for whom hysterectomy would have been the preferred treatment were recruited over 24 months and randomly allocated to hysterectomy (99 women) or to hysteroscopic surgery (transcervical resection (52 women) or laser ablation (53 women). MAIN OUTCOME MEASURES: Mental state, martial relationship, psychosocial and sexual adjustment in assessments conducted before the operation and one month, six months, and 12 months later. RESULTS: Both treatments significantly reduced the anxiety and depression present before the operation, and there were no differences in mental health between the groups at 12 months. Hysterectomy did not lead to postoperative psychiatric illness. Sexual interest after the operation did not vary with treatment. Overall, 46 out of 185 (25%) women reported a loss sexual interest and 50 out of 185 (27%) reported increased sexual interest. Marital relationships were unaffected by surgery. Personality and duration of dysfunctional uterine bleeding played no significant part in determining outcome. CONCLUSIONS: Hysteroscopic surgery and hysterectomy have a similar effect on psychiatric and psychosocial outcomes. There is no evidence that hysterectomy leads to postoperative psychiatric illness. PMID:8611783

The Effects of a Low-Carbohydrate Diet vs. a Low-Fat Diet on Novel Cardiovascular Risk Factors: A Randomized Controlled Trial.

PubMed

Hu, Tian; Yao, Lu; Reynolds, Kristi; Whelton, Paul K; Niu, Tianhua; Li, Shengxu; He, Jiang; Bazzano, Lydia A

2015-09-17

Increasing evidence supports a low-carbohydrate diet for weight loss and improvement in traditional cardiovascular disease (CVD) markers. Effects on novel CVD markers remain unclear. We examined the effects of a low-carbohydrate diet (<40 g/day; n = 75) versus a low-fat diet (<30% kcal/day from total fat, <7% saturated fat; n = 73) on biomarkers representing inflammation, adipocyte dysfunction, and endothelial dysfunction in a 12 month clinical trial among 148 obese adults free of diabetes and CVD. Participants met with a study dietitian on a periodic basis and each diet group received the same behavioral curriculum which included dietary instruction and supportive counseling. Eighty percent of participants completed the intervention. At 12 months, participants on the low-carbohydrate diet had significantly greater increases in adiponectin (mean difference in change, 1336 ng/mL (95% CI, 342 to 2330 ng/mL); p = 0.009) and greater decreases in intercellular adhesion molecule-1 concentrations (-16.8 ng/mL (-32.0 to -1.6 ng/mL); p = 0.031) than those on the low-fat diet. Changes in other novel CVD markers were not significantly different between groups. In conclusion, despite the differences in weight changes on diets, a low-carbohydrate diet resulted in similar or greater improvement in inflammation, adipocyte dysfunction, and endothelial dysfunction than a standard low-fat diet among obese persons.

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants

PubMed Central

Ten, Vadim S.

2017-01-01

At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units—alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise. PMID:27901512

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants.

PubMed

Ten, Vadim S

2017-02-01

At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units-alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise.

Visit-to-visit blood pressure variation is associated with outcomes in a U-shaped fashion in patients with myocardial infarction complicated with systolic dysfunction and/or heart failure: findings from the EPHESUS and OPTIMAAL trials.

PubMed

Ferreira, João Pedro; Duarte, Kévin; Pitt, Bertram; Dickstein, Kenneth; McMurray, John J V; Zannad, Faiez; Rossignol, Patrick

2018-04-21

Visit-to-visit office blood pressure variation (BPV) has prognostic implications independent from mean BP across several populations in the cardiovascular field. The association of BPV with outcomes in patients with myocardial infarction (MI) with systolic dysfunction and/or heart failure is yet to be determined. Two independent cohorts were assessed: the EPHESUS and the OPTIMAAL trials with a total of more than 12 000 patients. The primary outcome was all-cause death. BPV was calculated as a coefficient of variation, that is, the ratio of the SD to the mean BP along the postbaseline follow-up. Cox regression models were used to determine the associations between BPV and events. Compared with the middle and lower BPV tertiles, patients in the upper BPV tertile were older, more often women, hypertensive, diabetic, with peripheral artery disease, and had more frequent use of loop diuretics and ACEi/ARBs. They also had lower LVEF, hemoglobin, and eGFR (all P < 0.001). BPV was independently associated with worse prognosis in a U-shaped manner. In the EPHESUS trial, both low and high BPV were associated with higher rates of death (and also cardiovascular death and the composite of cardiovascular death/ cardiovascular hospitalization): adjusted hazard ratio (95% CI) for the outcome of death is 1.99 (1.68-2.36) for high BPV and is 1.60 (1.35-1.90) for low BPV. Similar results were observed in the OPTIMAAL trial population. In two independent cohorts of MI patients with systolic dysfunction and/or heart failure, BPV was associated with worse prognosis in a U-shaped manner independently of the mean BP.

21 CFR 886.1400 - Maddox lens.

Code of Federal Regulations, 2014 CFR

2014-04-01

... intended to be handheld or placed in a trial frame to evaluate eye muscle dysfunction. (b) Classification... the current good manufacturing practice requirements of the quality system regulation in part 820 of...

21 CFR 886.1400 - Maddox lens.

Code of Federal Regulations, 2010 CFR

2010-04-01

... intended to be handheld or placed in a trial frame to evaluate eye muscle dysfunction. (b) Classification... the current good manufacturing practice requirements of the quality system regulation in part 820 of...

21 CFR 886.1400 - Maddox lens.

Code of Federal Regulations, 2011 CFR

2011-04-01

... intended to be handheld or placed in a trial frame to evaluate eye muscle dysfunction. (b) Classification... the current good manufacturing practice requirements of the quality system regulation in part 820 of...

21 CFR 886.1400 - Maddox lens.

Code of Federal Regulations, 2013 CFR

2013-04-01

... intended to be handheld or placed in a trial frame to evaluate eye muscle dysfunction. (b) Classification... the current good manufacturing practice requirements of the quality system regulation in part 820 of...

21 CFR 886.1400 - Maddox lens.

Code of Federal Regulations, 2012 CFR

2012-04-01

... intended to be handheld or placed in a trial frame to evaluate eye muscle dysfunction. (b) Classification... the current good manufacturing practice requirements of the quality system regulation in part 820 of...

A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes.

PubMed

Hausenblas, Heather Ann; Heekin, Kacey; Mutchie, Heather Lee; Anton, Stephen

2015-07-01

Throughout the past three decades, increased scientific attention has been given to examining saffron's (Crocus sativus L.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression. The purpose of this systematic review is to examine and categorize the current state of scientific evidence from randomized controlled trials (RCTs) regarding the efficacy of saffron on psychological/behavioral outcomes. Electronic and non-electronic systematic searches were conducted to identify all relevant human clinical research on saffron. The search strategy was extensive and was designed according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)." Reference lists of articles that met the inclusion criteria were searched. Only English language studies were reviewed. Saffron trials in combination with other substances and saffron safety studies were considered, in accordance with the PRISMA statement. Included studies must have a control group. Included studies must measure a physiological and/or a behavioral outcome. The methodological quality of all included studies was independently evaluated by two reviewers using the Jadad score. Mean scores and P-values of measures were compared both inter- and intra-study for each parameter (i.e., depression). Twelve studies met our inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes of: major depressive disorder (n=6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n=4), and weight loss/snacking behaviors (n=1). The data from these studies support the efficacy of saffron as compared to placebo in improving the following conditions: depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition, saffron use was also effective in reducing excessive snacking behavior. Findings from initial clinical trials suggest that saffron may improve the symptoms and the effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings.

Infant Nutritional Status and Markers of Environmental Enteric Dysfunction are Associated with Midchildhood Anthropometry and Blood Pressure in Tanzania.

PubMed

Locks, Lindsey M; Mwiru, Ramadhani S; Mtisi, Expeditho; Manji, Karim P; McDonald, Christine M; Liu, Enju; Kupka, Roland; Kisenge, Rodrick; Aboud, Said; Gosselin, Kerri; Gillman, Matthew; Gewirtz, Andrew T; Fawzi, Wafaie W; Duggan, Christopher P

2017-08-01

To assess whether growth and biomarkers of environmental enteric dysfunction in infancy are related to health outcomes in midchildhood in Tanzania. Children who participated in 2 randomized trials of micronutrient supplements in infancy were followed up in midchildhood (4.6-9.8 years of age). Anthropometry was measured at age 6 and 52 weeks in both trials, and blood samples were available from children at 6 weeks and 6 months from 1 trial. Linear regression was used for height-for-age z-score, body mass index-for-age z-score, and weight for age z-score, and blood pressure analyses; log-binomial models were used to estimate risk of overweight, obesity, and stunting in midchildhood. One hundred thirteen children were followed-up. Length-for-age z-score at 6 weeks and delta length-for-age z-score from 6 to 52 weeks were associated independently and positively with height-for-age z-score and inversely associated with stunting in midchildhood. Delta weight-for-length and weight-for-age z-score were also positively associated with midchildhood height-for-age z-score. The 6-week and delta weight-for-length z-scores were associated independently and positively with midchildhood body mass index-for-age z-score and overweight, as was the 6-week and delta weight-for-age z-score. Delta length-for-age z-score was also associated with an increased risk of overweight in midchildhood. Body mass index-for-age z-score in midchildhood was associated positively with systolic blood pressure. Serum anti-flagellin IgA concentration at 6 weeks was also associated with increased blood pressure in midchildhood. Anthropometry at 6 weeks and growth in infancy independently predict size in midchildhood, while anti-flagellin IgA, a biomarker of environmental enteric dysfunction, in early infancy is associated with increased blood pressure in midchildhood. Interventions in early life should focus on optimizing linear growth while minimizing excess weight gain and environmental enteric dysfunction. ClinicalTrials.gov: NCT00197730 and NCT00421668. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Epithelial dysfunction associated with pyo-inflammatory diseases of the ENT organs].

PubMed

Petukhova, N A

The modern concept of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome associated with pyo-inflammatory ENT diseases is presented. It has provided a basis for the analysis of the initial stages of etiopathogenesis of acute and chronic inflammation in the ENT system including the mucous and associated lymphoid tissues as well as the Pirogov-Waldeyer limphopharyngeal ring making up the first protective barrier. The leading role of dysbiosis of synanthropic microflora and endotoxins of the Gram-negative bacteria in the mechanisms of regional responsiveness of the organism to the infection and chronic endotoxic aggression is demonstrated. The regional and synthetic mechanisms underlying the interaction between the external and internal media of the organism are subjected to the analysis with special reference to those operating in epithelium. The possible variants of the outcome of these processes are considered including both the recovery and the development of chronic inflammation. It has been proved that the exhaustion of the internal reserves for the stabilization of the epithelium-associated lymphoid tissue system including the Pirogov-Waldeyer limphopharyngeal ring leads to the formation of epithelial dysfunction as the initial stage of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome. It is concluded that the modern concept of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome is a fundamental interdisciplinary phenomenon.

Brain structural network topological alterations of the left prefrontal and limbic cortex in psychogenic erectile dysfunction.

PubMed

Chen, Jianhuai; Chen, Yun; Gao, Qingqiang; Chen, Guotao; Dai, Yutian; Yao, Zhijian; Lu, Qing

2018-05-01

Despite increasing understanding of the cerebral functional changes and structural abnormalities in erectile dysfunction, alterations in the topological organization of brain networks underlying psychogenic erectile dysfunction remain unclear. Here, based on the diffusion tensor image data of 25 patients and 26 healthy controls, we investigated the topological organization of brain structural networks and its correlations with the clinical variables using the graph theoretical analysis. Patients displayed a preserved overall small-world organization and exhibited a less connectivity strength in the left inferior frontal gyrus, amygdale and the right inferior temporal gyrus. Moreover, an abnormal hub pattern was observed in patients, which might disturb the information interactions of the remaining brain network. Additionally, the clustering coefficient of the left hippocampus was positively correlated with the duration of patients and the normalized betweenness centrality of the right anterior cingulate gyrus and the left calcarine fissure were negatively correlated with the sum scores of the 17-item Hamilton Depression Rating Scale. These findings suggested that the damaged white matter and the abnormal hub distribution of the left prefrontal and limbic cortex might contribute to the pathogenesis of psychogenic erectile dysfunction and provided new insights into the understanding of the pathophysiological mechanisms of psychogenic erectile dysfunction.

Non-Exertional Heatstroke: A Case Report and Review of the Literature

PubMed Central

Mozzini, Chiara; Xotta, Giovanni; Garbin, Ulisse; Pasini, Anna Maria Fratta; Cominacini, Luciano

2017-01-01

Patient: Female, 41 Final Diagnosis: Heatstroke Symptoms: Coma Medication: — Clinical Procedure: Intensive Care Unit-Internal Medicine Specialty: Critical Care Medicine Objective: Rare co-existance of disease or pathology Background: Heatstroke (HS) is a life-threatening condition characterized by an elevation of the core body temperature above 40°C, central nervous system dysfunction, and possible multi-organ failure. HS can trigger systemic inflammation, disseminated intravascular coagulation (DIC), rhabdomyolysis, cerebral edema and seizures, pulmonary edema, heart dysfunctions, and renal and hepatic failure. Case Report: We report the case of a 41-year-old Romanian woman with a history of alcoholism who developed HS after arriving by bus in Verona, Italy in June 2016. The patient developed consecutive multi-organ dysfunction, including liver and renal failure, rhabdomyolysis, DIC, and arrhythmia. The patient was successfully treated with conservative measures. After 17 days, she recovered completely. Conclusions: The exact mechanism of HS-related multiple organ dysfunction is not completely understood and its pathogenesis is complex. It involves inflammation, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Development of a model in which chronic alcohol abuse alters oxidative, inflammatory, and ER stress response could also be a conceivable solution to the positive prognosis of severe HS patients, in which liver failure has a prominent role. PMID:28974669

Decreased Autophagy Contributes to Myocardial Dysfunction in Rats Subjected to Nonlethal Mechanical Trauma

PubMed Central

Liang, Feng; Li, Xiaoyu; Wang, Li; Yang, Caihong; Yan, Zi; Zhang, Suli; Liu, Huirong

2013-01-01

Autophagy is important in cells for removing damaged organelles, such as mitochondria. Insufficient autophagy plays a critical role in tissue injury and organ dysfunction under a variety of pathological conditions. However, the role of autophagy in nonlethal traumatic cardiac damage remains unclear. The aims of the present study were to investigate whether nonlethal mechanical trauma may result in the change of cardiomyocyte autophagy, and if so, to determine whether the changed myocardial autophagy may contribute to delayed cardiac dysfunction. Male adult rats were subjected to nonlethal traumatic injury, and cardiomyocyte autophagy, cardiac mitochondrial function, and cardiac function in isolated perfused hearts were detected. Direct mechanical traumatic injury was not observed in the heart within 24 h after trauma. However, cardiomyocyte autophagy gradually decreased and reached a minimal level 6 h after trauma. Cardiac mitochondrial dysfunction was observed by cardiac radionuclide imaging 6 h after trauma, and cardiac dysfunction was observed 24 h after trauma in the isolated perfused heart. These were reversed when autophagy was induced by administration of the autophagy inducer rapamycin 30 min before trauma. Our present study demonstrated for the first time that nonlethal traumatic injury caused decreased autophagy, and decreased autophagy may contribute to post-traumatic organ dysfunction. Though our study has some limitations, it strongly suggests that cardiac damage induced by nonlethal mechanical trauma can be detected by noninvasive radionuclide imaging, and induction of autophagy may be a novel strategy for reducing posttrauma multiple organ failure. PMID:23977036

Cardiovascular and systemic effects of gastric dilatation and volvulus in dogs.

PubMed

Sharp, Claire R; Rozanski, Elizabeth A

2014-09-01

Gastric dilatation and volvulus (GDV) is a common emergency condition in large and giant breed dogs that is associated with high morbidity and mortality. Dogs with GDV classically fulfill the criteria for the systemic inflammatory response syndrome (SIRS) and can go on to develop multiple organ dysfunction syndrome (MODS). Previously reported organ dysfunctions in dogs with GDV include cardiovascular, respiratory, gastrointestinal, coagulation and renal dysfunction. Cardiovascular manifestations of GDV include shock, cardiac arrhythmias and myocardial dysfunction. Respiratory dysfunction is also multifactorial, with contributory factors including decreased respiratory excursion due to gastric dilatation, decreased pulmonary perfusion and aspiration pneumonia. Gastrointestinal dysfunction includes gastric necrosis and post-operative gastrointestinal upset such as regurgitation, vomiting, and ileus. Coagulation dysfunction is another common feature of MODS in dogs with GDV. Disseminated intravascular coagulation can occur, putting them at risk of complications associated with thrombosis in the early hypercoagulable state and hemorrhage in the subsequent hypocoagulable state. Acute kidney injury, acid-base and electrolyte disturbances are also reported in dogs with GDV. Understanding the potential for systemic effects of GDV allows the clinician to monitor patients astutely and detect such complications early, facilitating early intervention to maximize the chance of successful management. Copyright © 2014 Elsevier Inc. All rights reserved.

Targeting Endothelial Function to Treat Heart Failure with Preserved Ejection Fraction: The Promise of Exercise Training

PubMed Central

Lemmens, Katrien; Vrints, Christiaan J.

2017-01-01

Although the burden of heart failure with preserved ejection fraction (HFpEF) is increasing, there is no therapy available that improves prognosis. Clinical trials using beta blockers and angiotensin converting enzyme inhibitors, cardiac-targeting drugs that reduce mortality in heart failure with reduced ejection fraction (HFrEF), have had disappointing results in HFpEF patients. A new “whole-systems” approach has been proposed for designing future HFpEF therapies, moving focus from the cardiomyocyte to the endothelium. Indeed, dysfunction of endothelial cells throughout the entire cardiovascular system is suggested as a central mechanism in HFpEF pathophysiology. The objective of this review is to provide an overview of current knowledge regarding endothelial dysfunction in HFpEF. We discuss the molecular and cellular mechanisms leading to endothelial dysfunction and the extent, presence, and prognostic importance of clinical endothelial dysfunction in different vascular beds. We also consider implications towards exercise training, a promising therapy targeting system-wide endothelial dysfunction in HFpEF. PMID:28706575

Randomized clinical trial assessing whether additional massage treatments for chronic neck pain improve 12- and 26-week outcomes.

PubMed

Cook, Andrea J; Wellman, Robert D; Cherkin, Daniel C; Kahn, Janet R; Sherman, Karen J

2015-10-01

This is the first study to systematically evaluate the value of a longer treatment period for massage. We provide a framework of how to conceptualize an optimal dose in this challenging setting of nonpharmacologic treatments. The aim was to determine the optimal dose of massage for neck pain. Two-phase randomized trial for persons with chronic nonspecific neck pain. Primary randomization to one of five groups receiving 4 weeks of massage (30 minutes 2x/or 3x/wk or 60 minutes 1x, 2x, or 3x/wk). Booster randomization of participants to receive an additional six massages, 60 minutes 1x/wk, or no additional massage. A total of 179 participants from Group Health and the general population of Seattle, WA, USA recruited between June 2010 and August 2011 were included. Primary outcomes self-reported neck-related dysfunction (Neck Disability Index) and pain (0-10 scale) were assessed at baseline, 12, and 26 weeks. Clinically meaningful improvement was defined as greater than or equal to 5-point decrease in dysfunction and greater than or equal to 30% decrease in pain from baseline. Clinically meaningful improvement for each primary outcome with both follow-up times was analyzed using adjusted modified Poisson generalized estimating equations (GEEs). Secondary analyses for the continuous outcomes used linear GEEs. There were no observed differences by primary treatment group at 12 or 26 weeks. Those receiving booster dose had improvements in both dysfunction and pain at 12 weeks (dysfunction: relative risk [RR]=1.56 [1.08-2.25], p=.018; pain: RR=1.25 [0.98-1.61], p=.077), but those were nonsignificant at 26 weeks (dysfunction: RR=1.22 [0.85-1.74]; pain: RR=1.09 [0.82-1.43]). Subgroup analysis by primary and booster treatments found the booster dose only effective among those initially randomized to one of the 60-minute massage groups. "Booster" doses for those initially receiving 60 minutes of massage should be incorporated into future trials of massage for chronic neck pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal mortality and derivations from the WHO near-miss tool: An institutional experience over a decade in Southern India.

PubMed

Halder, Ajay; Jose, Ruby; Vijayselvi, Reeta

2014-01-01

Preceding the use of World Health Organization (WHO) near-miss approach in our institute for the surveillance of Severe Maternal Outcome (SMO), we pilot-tested the tool on maternal death cases that took place over the last 10 years in order to establish its feasibility and usefulness at the institutional level. This was a retrospective review of maternal deaths in Christian Medical College Vellore, India, over a decade. Cases were recorded and analyzed using the WHO near-miss tool. The International Classification of Diseases, 10(th) Revision was used to define and classify maternal mortality. There were 98,139 total births and 212 recorded maternal deaths. Direct causes of mortality constituted 46.96% of total maternal deaths, indirect causes constituted 51.40%, and unknown cases constituted 1.9%. Nonobstetrical cause (48.11%) is the single largest group. Infections (19.8%) other than puerperal sepsis remain an important group, with pulmonary tuberculosis, scrub typhus, and malaria being the leading ones. According to the WHO near-miss criteria, cardiovascular and respiratory dysfunctions are the most frequent organ dysfunctions. Incidence of coagulation dysfunction is seen highest in obstetrical hemorrhage (64%). All women who died had at least one organ dysfunction; 90.54% mothers had two- and 38.52% had four- or more organ involvement. The screening questions of the WHO near-miss tool are particularly instrumental in obtaining a comprehensive assessment of the problem beyond the International Classification of Diseases-Maternal Mortality and establish the need for laboratory-based identification of organ dysfunctions and prompt availability of critical care facilities. The process indicators, on the other hand, inquire about the basic interventions that are more or less widely practiced and therefore give no added information at the institutional level.

A Nonerythropoietic Peptide that Mimics the 3D Structure of Erythropoietin Reduces Organ Injury/Dysfunction and Inflammation in Experimental Hemorrhagic Shock

PubMed Central

Patel, Nimesh SA; Nandra, Kiran K; Brines, Michael; Collino, Massimo; Wong, WS Fred; Kapoor, Amar; Benetti, Elisa; Goh, Fera Y; Fantozzi, Roberto; Cerami, Anthony; Thiemermann, Christoph

2011-01-01

Recent studies have shown that erythropoietin, critical for the differentiation and survival of erythrocytes, has cytoprotective effects in a wide variety of tissues, including the kidney and lung. However, erythropoietin has been shown to have a serious side effect—an increase in thrombovascular effects. We investigated whether pyroglutamate helix B-surface peptide (pHBSP), a nonerythropoietic tissue-protective peptide mimicking the 3D structure of erythropoietin, protects against the organ injury/ dysfunction and inflammation in rats subjected to severe hemorrhagic shock (HS). Mean arterial blood pressure was reduced to 35 ± 5 mmHg for 90 min followed by resuscitation with 20 mL/kg Ringer Lactate for 10 min and 50% of the shed blood for 50 min. Rats were euthanized 4 h after the onset of resuscitation. pHBSP was administered 30 min or 60 min into resuscitation. HS resulted in significant organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung). In rats subjected to HS, pHBSP significantly attenuated (i) organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung), (ii) increased the phosphorylation of Akt, glycogen synthase kinase-3β and endothelial nitric oxide synthase, (iii) attenuated the activation of nuclear factor (NF)-κB and (iv) attenuated the increase in p38 and extracellular signal-regulated kinase (ERK)1/2 phosphorylation. pHBSP protects against multiple organ injury/dysfunction and inflammation caused by severe hemorrhagic shock by a mechanism that may involve activation of Akt and endothelial nitric oxide synthase, and inhibition of glycogen synthase kinase-3β and NF-κB. PMID:21607291

Effects of red-cell storage duration on patients undergoing cardiac surgery.

PubMed

Steiner, Marie E; Ness, Paul M; Assmann, Susan F; Triulzi, Darrell J; Sloan, Steven R; Delaney, Meghan; Granger, Suzanne; Bennett-Guerrero, Elliott; Blajchman, Morris A; Scavo, Vincent; Carson, Jeffrey L; Levy, Jerrold H; Whitman, Glenn; D'Andrea, Pamela; Pulkrabek, Shelley; Ortel, Thomas L; Bornikova, Larissa; Raife, Thomas; Puca, Kathleen E; Kaufman, Richard M; Nuttall, Gregory A; Young, Pampee P; Youssef, Samuel; Engelman, Richard; Greilich, Philip E; Miles, Ronald; Josephson, Cassandra D; Bracey, Arthur; Cooke, Rhonda; McCullough, Jeffrey; Hunsaker, Robert; Uhl, Lynne; McFarland, Janice G; Park, Yara; Cushing, Melissa M; Klodell, Charles T; Karanam, Ravindra; Roberts, Pamela R; Dyke, Cornelius; Hod, Eldad A; Stowell, Christopher P

2015-04-09

Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).

Multi-organ dysfunction due to bath salts: are we aware of this entity?

PubMed

Valsalan, Rohith; Varghese, Benoj; Soman, Diya; Buckmaster, Jonathan; Yew, Steven; Cooper, David

2017-01-01

Methylenedioxypyrovalerone (MDPV) is a synthetic, cathinone-derivative, central nervous system stimulant taken to produce a cocaine- or methamphetamine-like high. Physical manifestations include tachycardia, hypertension, arrhythmias, hyperthermia, sweating, rhabdomyolysis, hyperkalaemia, disseminated intravascular coagulation, oliguria and seizures. We report a patient who presented with severe metabolic acidosis, multi-organ dysfunction, rhabdomyolysis, hyperkalaemia and seizures. This case highlights that even though a urine drug screen for routine psychostimulant drugs is negative, clinicians need to be vigilant about the adverse effects of MDPV as a possible cause of multi-organ dysfunction. Substances such as this can only be detected by special tests, such as gas/liquid chromatography mass spectrometry. This is the first reported case of MDPV toxicity successfully treated in Australia to the best of our knowledge. © 2017 Royal Australasian College of Physicians.

Effect of Gum Arabic (Acacia Senegal) supplementation on visceral adiposity index (VAI) and blood pressure in patients with type 2 diabetes mellitus as indicators of cardiovascular disease (CVD): a randomized and placebo-controlled clinical trial.

PubMed

Babiker, Rasha; Elmusharaf, Khalifa; Keogh, Michael B; Saeed, Amal M

2018-03-20

There is a strong association between cardiometabolic risk and adipose tissue dysfunction with great consequences on type 2 diabetic patients. Visceral Adiposity Index (VAI) is an indirect clinical marker of adipose tissue dysfunction. Gum Arabic (GA) is a safe dietary fiber, an exudate of Acacia Senegal. Gum Arabic had shown lipid lowering effect in both humans and animals. The aim of this trial was to determine the effect of GA supplementation on anthropometric obesity marker, Visceral Adiposity Index (VAI) and blood pressure in patients with type 2 diabetes mellitus. This randomized, double blinded, placebo controlled trial recruited a total of 91 type 2 diabetic patients (73 females, 18 males), age (mean ± SD) 50.09 ± 9.3 years on hypoglycemic agents and were randomly assigned into two groups, either to consume 30 g of GA or 5 g of placebo daily for 3 months. Anthropometric obesity markers were measured and indices were calculated. Blood pressure was measured and high density lipoprotein (HDL) and triglycerides (TG) were determined in fasting blood samples at the start and end of the study period. After intervention, Gum Arabic decreased BMI and VAI significantly (P < 0.05) in GA group by 2 and 23.7% respectively. Body adiposity index significantly decreased by 3.9% in GA group while there were no significant changes in waist circumference or waist-to-hip ratio (WHR). Systolic blood pressure significantly decreased by 7.6% in GA group and by 2.7% in placebo group from baseline with no significant changes in diastolic blood pressure in the two groups. Gum Arabic consumption at a dose of 30 g/d for 3 months may play an effective role in preventing weight gain and modulating adipose tissue dysfunction in type 2 diabetic patients, although no effect has been shown in waist-to-hip ratio. The trial had been registered as prospective interventional clinical trials in the Pan African Clinical Trial Registry (PACTR) PACTR201403000785219 , on 7th March 2014.

Restrictive versus liberal transfusion strategies for older mechanically ventilated critically ill patients: a randomized pilot trial.

PubMed

Walsh, Timothy S; Boyd, Julia A; Watson, Douglas; Hope, David; Lewis, Steff; Krishan, Ashma; Forbes, John F; Ramsay, Pamela; Pearse, Rupert; Wallis, Charles; Cairns, Christopher; Cole, Stephen; Wyncoll, Duncan

2013-10-01

To compare hemoglobin concentration (Hb), RBC use, and patient outcomes when restrictive or liberal blood transfusion strategies are used to treat anemic (Hb≤90 g/L) critically ill patients of age≥55 years requiring≥4 days of mechanical ventilation in ICU. Parallel-group randomized multicenter pilot trial. Six ICUs in the United Kingdom participated between August 2009 and December 2010. One hundred patients (51 restrictive and 49 liberal groups). Patients were randomized to a restrictive (Hb trigger, 70 g/L; target, 71-90 g/L) or liberal (90 g/L; target, 91-110 g/L) transfusion strategy for 14 days or the remainder of ICU stay, whichever was longest. Baseline comorbidity rates and illness severity were high, notably for ischemic heart disease (32%). The Hb difference among groups was 13.8 g/L (95% CI, 11.5-16.0 g/L); p<0.0001); mean Hb during intervention was 81.9 (SD, 5.1) versus 95.7 (6.3) g/L; 21.6% fewer patients in the restrictive group were transfused postrandomization (p<0.001) and received a median 1 (95% CI, 1-2; p=0.002) fewer RBC units. Protocol compliance was high. No major differences in organ dysfunction, duration of ventilation, infections, or cardiovascular complications were observed during intensive care and hospital follow-up. Mortality at 180 days postrandomization trended toward higher rates in the liberal group (55%) than in the restrictive group (37%); relative risk was 0.68 (95% CI, 0.44-1.05; p=0.073). This trend remained in a survival model adjusted for age, gender, ischemic heart disease, Acute Physiology and Chronic Health Evaluation II score, and total non-neurologic Sequential Organ Failure Assessment score at baseline (hazard ratio, 0.54 [95% CI, 0.28-1.03]; p=0.061). A large trial of transfusion strategies in older mechanically ventilated patients is feasible. This pilot trial found a nonsignificant trend toward lower mortality with restrictive transfusion practice.

Patterned feeding experience for preterm infants: study protocol for a randomized controlled trial.

PubMed

Pickler, Rita H; Wetzel, Paul A; Meinzen-Derr, Jareen; Tubbs-Cooley, Heather L; Moore, Margo

2015-06-04

Neurobehavioral disabilities occur in 5-15% of preterm infants with an estimated 50-70% of very low birth weight preterm infants experiencing later dysfunction, including cognitive, behavioral, and social delays that often persist into adulthood. Factors implicated in poor neurobehavioral and developmental outcomes are hospitalization in the neonatal intensive care unit (NICU) and inconsistent caregiving patterns. Although much underlying brain damage occurs in utero or shortly after birth, neuroprotective strategies can stop lesions from progressing, particularly when these strategies are used during the most sensitive periods of neural plasticity occurring months before term age. The purpose of this randomized trial is to test the effect of a patterned feeding experience on preterm infants' neurobehavioral organization and development, cognitive function, and clinical outcomes. This trial uses an experimental, longitudinal, 2-group design with 120 preterm infants. Infants are enrolled within the first week of life and randomized to an experimental group receiving a patterned feeding experience from the first gavage feeding through discharge or to a control group receiving usual feeding care experience. The intervention involves a continuity of tactile experiences associated with feeding to train and build neuronal networks supportive of normal infant feeding experience. Primary outcomes are neurobehavioral organization as measured by Neurobehavioral Assessment of the Preterm Infant at 3 time points: the transition to oral feedings, NICU discharge, and 2 months corrected age. Secondary aims are cognitive function measured using the Bayley Scales of Infant and Toddler Development, Third Edition at 6 months corrected age, neurobehavioral development (sucking organization, feeding performance, and heart rate variability), and clinical outcomes (length of NICU stay and time to full oral feeding). The potential effects of demographic and biobehavioral factors (perinatal events and conditions of maternal or fetal/newborn origin and immunologic and genetic biomarkers) on the outcome variables will also be considered. Theoretically, the intervention provided at a critical time in neurologic system development and associated with a recurring event (feeding) should enhance neural connections that may be important for later development, particularly language and other cognitive and neurobehavioral organization skills. NCT01577615 11 April 2012.

Pelvic-Floor-Muscle Training Adherence: Tools, Measurements and Strategies-2011 ICS State-of-the-Science Seminar Research Paper II of IV.

PubMed

Dumoulin, Chantal; Alewijnse, Dianne; Bo, Kari; Hagen, Suzanne; Stark, Diane; Van Kampen, Marijke; Herbert, Julia; Hay-Smith, Jean; Frawley, Helena; McClurg, Doreen; Dean, Sarah

2015-09-01

This paper on pelvic-floor-muscle training (PFMT) adherence, the second of four from the International Continence Society's 2011 State-of-the-Science Conference, aims to (1) identify and collate current adherence outcome measures, (2) report the determinants of adherence, (3) report on PFMT adherence strategies, and (4) make actionable clinical and research recommendations. Data were amassed from a literature review and an expert panel (2011 conference), following consensus statement methodology. Experts in pelvic floor dysfunction collated and synthesized the evidence and expert opinions on PFMT adherence for urinary incontinence (UI) and lower bowel dysfunction in men and women and pelvic organ prolapse in women. The literature was scarce for most of the studied populations except for limited research on women with UI. Exercise diaries were the most widely-used adherence outcome measure, PFMT adherence was inconsistently monitored and inadequately reported. Determinants: Research, mostly secondary analyses of RCTs, suggested that intention to adhere, self-efficacy expectations, attitudes towards the exercises, perceived benefits and a high social pressure to engage in PFMT impacted adherence. Few trials studied and compared adherence strategies. A structured PFMT programme, an enthusiastic physiotherapist, audio prompts, use of established theories of behavior change, and user-consultations seem to increase adherence. The literature on adherence outcome measures, determinants and strategies remains scarce for the studied populations with PFM dysfunction, except in women with UI. Although some current adherence findings can be applied to clinical practice, more effective and standardized research is urgently needed across all the sub-populations. © 2015 Wiley Periodicals, Inc.

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

PubMed Central

2013-01-01

Abstract Significance: Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. Recent Advances: Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is available. The characteristics of severe sepsis include ascorbate (reduced vitamin C) depletion, excessive protein nitration in microvascular endothelial cells, and microvascular dysfunction composed of refractive vasodilation, endothelial barrier dysfunction, and disseminated intravascular coagulation. Parenteral administration of ascorbate prevents or even reverses these pathological changes and thereby decreases hypotension, edema, multiorgan failure, and death in animal models of sepsis. Critical Issues: Dehydroascorbic acid appears to be as effective as ascorbate for protection against microvascular dysfunction, organ failure, and death when injected in sepsis models, but information about pharmacodynamics and safety in human subjects is only available for ascorbate. Although the plasma ascorbate concentration in critically ill and septic patients is normalized by repletion protocols that use high doses of parenteral ascorbate, and such doses are tolerated well by most healthy subjects, whether such large amounts of the vitamin trigger adverse effects in patients is uncertain. Future Directions: Further study of sepsis models may determine if high concentrations of ascorbate in interstitial fluid have pro-oxidant and bacteriostatic actions that also modify disease progression. However, the ascorbate depletion observed in septic patients receiving standard care and the therapeutic mechanisms established in models are sufficient evidence to support clinical trials of parenteral ascorbate as an adjuvant therapy for sepsis. Antioxid. Redox Signal. 19, 2129–2140. PMID:23682970

Cannabidiol limits Tcell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and organ transplantation.

PubMed

Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V; Liaudet, Lucas; Haskó, György; Čiháková, Daniela; Mechoulam, Raphael; Pacher, Pal

2016-01-08

Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a non-psychoactive constituent of Marijuana which exerts antiinflammatory effects independent from classical cannabinoid receptors. Recently 80 clinical trials have been reported investigating the effects of CBD in various diseases from inflammatory bowel disease to graft-versus-host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received FDA approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T cell-infiltration, profound inflammatory response, fibrosis (measured by qRT-PCR, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.

Cannabidiol Limits T Cell–Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

PubMed Central

Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V; Liaudet, Lucas; Hask’, György; ’iháková, Daniela; Mechoulam, Raphael; Pacher, Pal

2016-01-01

Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a nonpsychoactive constituent of marijuana that exerts antiinflammatory effects independent of classical cannabinoid receptors. Recently, 80 clinical trials have investigated the effects of CBD in various diseases from inflammatory bowel disease to graft versus host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received U.S. Food and Drug Administration approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell–mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T-cell infiltration, profound inflammatory response and fibrosis (measured by quantitative real-time polymerase chain reaction, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with a pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ T cell–mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation. PMID:26772776

A novel apparatus for non-contact measurement of heart rate variability: a system to prevent secondary exposure of medical personnel to toxic materials under biochemical hazard conditions, in monitoring sepsis or in predicting multiple organ dysfunction syndrome.

PubMed

Matsui, T; Arai, I; Gotoh, S; Hattori, H; Takase, B; Kikuchi, M; Ishihara, M

2005-10-01

The impaired balance of the low-frequency/high-frequency ratio obtained from spectral components of RR intervals can be a diagnostic test for sepsis. In addition, it is known that a reduction of heart rate variability (HRV) is useful in identifying septic patients at risk of the development of multiple organ dysfunction syndrome (MODS). We have reported a non-contact method using a microwave radar to monitor the heart and respiratory rates of a healthy person placed inside an isolator or of experimental animals exposed to toxic materials. With the purpose of preventing secondary exposure of medical personnel to toxic materials under biochemical hazard conditions, we designed a novel apparatus for non-contact measurement of HRV using a 1215 MHz microwave radar, a high-pass filter, and a personal computer. The microwave radar monitors only the small reflected waves from the subject's chest wall, which are modulated by the cardiac and respiratory motion. The high-pass filter enhances the cardiac signal and attenuates the respiratory signal. In a human trial, RR intervals derived from the non-contact apparatus significantly correlated with those derived from ECG (r=0.98, P<0.0001). The non-contact apparatus showed a similar power spectrum of RR intervals to that of ECG. Our non-contact HRV measurement apparatus appears promising for future pre-hospital monitoring of septic patients or for predicting MODS patients, inside isolators or in the field for mass casualties under biochemical hazard circumstances.

Solid organ transplantation following end-organ failure in recipients of hematopoietic stem cell transplantation in children.

PubMed

Upadhyay, Kiran; Fine, Richard N

2014-08-01

Hematopoietic stem cell transplantation (HSCT) is an accepted treatment modality for various malignant and non-malignant disorders of the lympho-hematopoietic system. Patient survival rate has increased significantly with the use of this procedure. However, with the increase in disease-free patient survival rates, complications including various organ toxicities are also common. Kidney, liver, lung, heart, and skin are among those solid organs that are commonly affected and frequently lead to organ dysfunction and eventually end-organ disease. Conservative measures may or may not be successful in managing the organ failure in these patients. Solid organ transplantation has been shown to be promising in those patients who fail conservative management. This review will summarize the causes of solid organ (kidney, liver, and lung) dysfunction and the available data on transplantation of these solid organs in post-HSCT recipients.

The Current Status of Stem-Cell Therapy in Erectile Dysfunction: A Review

PubMed Central

Reed-Maldonado, Amanda B

2016-01-01

Stem cells are undifferentiated cells that are capable of renewal and repair of tissue due to their capacity for division and differentiation. The purpose of this review is to describe recent advances in the use of stem cell (SC) therapy for male erectile dysfunction (ED). We performed a MEDLINE database search of all relevant articles regarding the use of SCs for ED. We present a concise summary of the scientific principles behind the usage of SC for ED. We discuss the different types of SCs, delivery methods, current pre-clinical literature, and published clinical trials. Four clinical trials employing SC for ED have been published. These articles are summarized in this review. All four report improvements in ED after SC therapy. SC therapy remains under investigation for the treatment of ED. It is reassuring that clinical trials thus far have reported positive effects on erectile function and few adverse events. Safety and methodical concerns about SC acquisition, preparation and delivery remain and require continued investigation prior to wide-spread application of these methods. PMID:28053944

Psychological Correlates of Sexual Dysfunction in Female Rectal and Anal Cancer Survivors: Analysis of Baseline Intervention Data

PubMed Central

Philip, Errol J.; Nelson, Christian; Temple, Larissa; Carter, Jeanne; Schover, Leslie; Jennings, Sabrina; Jandorf, Lina; Starr, Tatiana; Baser, Ray; DuHamel, Katherine

2013-01-01

Introduction Sexual dysfunction represents a complex and multifactorial construct that can affect both men and women and has been noted to often deteriorate significantly after treatment for rectal and anal cancer. Despite this, it remains an understudied, underreported and undertreated issue in the field of cancer survivorship. Aim This study examined the characteristics of women enrolled in an intervention trial to treat sexual dysfunction, and explored the relationship between sexual functioning and psychological well-being. Main Outcomes Measures Quality of life (EORTC-QLQ-C30 & QLQ-CR38), sexual functioning (FSFI) and psychological well-being (BSI Depression/Anxiety, IES-R, CR-38 Body Image). Methods There were 70 female post-treatment anal or rectal cancer survivors assessed as part of the current study. Participants were enrolled in a randomized intervention trial to treat sexual dysfunction and completed outcome measures prior to randomization. Results Women enrolled in the study intervention were on average 55 years old, predominantly Caucasian (79%), married (57%) and a median of 4 years post-primary treatment. For those reporting sexual activity at baseline (N=41), sexual dysfunction was associated with a range of specific measures of psychological well-being, all in the hypothesized direction. The Sexual/Relationship Satisfaction subscale was associated with all measures of psychological well-being (r=−.45 to −.70, all p<.01). Body image, anxiety and cancer-specific post-traumatic distress were notable in their association with subscales of sexual functioning, while a global quality of life measure was largely unrelated. Conclusions For sexually-active female rectal and anal cancer survivors enrolled in a sexual health intervention, sexual dysfunction was significantly and consistently associated with specific measures of psychological well-being, most notably Sexual/Relationship Satisfaction. These results suggest that sexual functioning may require focused assessment by providers, beyond broad quality of life assessments, and that attention to Sexual/Relationship Satisfaction may be critical in the development and implementation of interventions for this cohort of patients. PMID:23551928

The Perioperative Educational Program for Improving Upper Arm Dysfunction in Patients with Breast Cancer at 1-Year Follow-Up: A Prospective, Controlled Trial.

PubMed

Sato, Fumiko; Arinaga, Yoko; Sato, Naoko; Ishida, Takanori; Ohuchi, Noriaki

2016-03-01

The many women with breast cancer who underwent axillary lymph node dissection (ALND) suffer from the upper arm dysfunction. In this study, we investigated the effectiveness of a perioperative educational program for improving upper arm dysfunction in breast cancer patients following ALND. This study was a sub-analysis of a previous controlled trial with an educational program. The subjects of this analysis included 64 patients following ALND who completed measurements at 12 months. The perioperative educational program consisted of monitoring of arm dysfunction, exercises, massage, and lifestyle adjustments. The intervention group (37 patients) received this perioperative educational program over 12 months, while 27 patients in the control group received written information about shoulder exercise from on-site staff only before surgery. Primary outcomes were shoulder range of motion (ROM), arm girth, and grip strength. Secondary outcomes were evaluated with the Subjective Perception of Post-Operative Functional Impairment of the Arm (SPOFIA) scores, the Disabilities of the Arm, Shoulder and Hand (DASH) scores, and the Medical Outcome Study 36-Item Short-Form Health Survey v2 (SF-36v2). The SF-36v2 measures health-related quality of life (QOL). Primary and secondary outcomes were compared between groups at 1 week (after drainage tube removal) and 12 months after surgery, using the Mann-Whitney U test. The horizontal extension was significantly improved only in the intervention group. Moreover, the SPOFIA score was significantly improved in the intervention group, and other scores of the secondary outcomes were similar between the two groups. The perioperative educational program may improve postoperative upper arm dysfunction and symptoms.

The Dysfunctions of Bureaucratic Structure.

ERIC Educational Resources Information Center

Duttweiler, Patricia Cloud

1988-01-01

Numerous dysfunctions result from bureaucratic school organization, including an overemphasis on specialized tasks, routine operating rules, and formal procedures for managing teaching and learning. Such schools are characterized by numerous regulations; formal communications; centralized decision making; and sharp distinctions among…

[Channels: a new way to revisit pathology].

PubMed

Fournier, Emmanuel

2014-02-01

Many "essential" diseases that manifest themselves in the form of crises or fits (epilepsies, episodic ataxia, periodic paralyses, myotonia, heart rhythm disorders, etc.) are due to ionic channel dysfunction and are thus referred to as "channelopathies". Some of these disorders are congenital, due to mutations of genes encoding channel subunits, while others result from toxic, immune or hormonal disturbances affecting channelfunction. Channelopathies take on a wide variety of clinical forms, depending on the type of channel (sodium, potassium, calcium, chloride...) and the type of dysfunction (loss or gain of function). Some apparently unrelated diseases affecting distinct organs are due to a similar dysfunction of the same channel, revealing unsuspected relationships between organs and between medical specialties. In addition, a given syndrome can be caused by distinct channel dysfunctions. This provides new opportunities for diferential diagnosis and specific correction of the causal defects, although some treatments find applications across multiple medical specialties.

The perils of dimensionalization: challenges in distinguishing negative traits from personality disorders.

PubMed

Wakefield, Jerome C

2008-09-01

The harmful dysfunction analysis of mental disorder is used to assess whether traits are indicative of personality disorder, and the ways such an inference can go wrong. Personality is an overall organization that allows the organism to accomplish basic goals within the constraints of its basic traits and specific intentional states. Extreme traits can be negative or "dysfunctional" in the sense that they interfere with the achievement of socially or personally valued goals; however, they are not necessarily dysfunctions or disorders in the biological or medical sense. Thus, no sheer assessment of a set of traits can offer sufficient information for a diagnosis of personality disorder. Nor do criteria such as maladaptiveness, impairment, or clinical significance necessarily transform a trait into a personality disorder. The DSM's most plausible suggestion for judging when traits are dysfunctions, inflexibility, is also problematic because many nondisordered traits are inflexible as well.

Emerging pharmacotherapy for cancer patients with cognitive dysfunction

PubMed Central

2013-01-01

Advances in the diagnosis and multi-modality treatment of cancer have increased survival rates for many cancer types leading to an increasing load of long-term sequelae of therapy, including that of cognitive dysfunction. The cytotoxic nature of chemotherapeutic agents may also reduce neurogenesis, a key component of the physiology of memory and cognition, with ramifications for the patient’s mood and other cognition disorders. Similarly radiotherapy employed as a therapeutic or prophylactic tool in the treatment of primary or metastatic disease may significantly affect cognition. A number of emerging pharmacotherapies are under investigation for the treatment of cognitive dysfunction experienced by cancer patients. Recent data from clinical trials is reviewed involving the stimulants modafinil and methylphenidate, mood stabiliser lithium, anti-Alzheimer’s drugs memantine and donepezil, as well as other agents which are currently being explored within dementia, animal, and cell culture models to evaluate their use in treating cognitive dysfunction. PMID:24156319

Intratracheal Milrinone Bolus Administration During Acute Right Ventricular Dysfunction After Cardiopulmonary Bypass.

PubMed

Gebhard, Caroline Eva; Desjardins, Georges; Gebhard, Cathérine; Gavra, Paul; Denault, André Y

2017-04-01

To evaluate intratracheal milrinone (tMil) administration for rapid treatment of right ventricular (RV) dysfunction as a novel route after cardiopulmonary bypass. Retrospective analysis. Single-center study. The study comprised 7 patients undergoing cardiac surgery who exhibited acute RV dysfunction after cardiopulmonary bypass. After difficult weaning caused by cardiopulmonary bypass-induced acute RV dysfunction, milrinone was administered as a 5-mg bolus inside the endotracheal tube. RV function improvement, as indicated by decreasing pulmonary artery pressure and changes of RV waveforms, was observed in all 7 patients. Adverse effects of tMil included dynamic RV outflow tract obstruction (2 patients) and a decrease in systemic mean arterial pressure (1 patient). tMil may be an effective, rapid, and easily applicable therapeutic alternative to inhaled milrinone for the treatment of acute RV failure during cardiac surgery. However, sufficiently powered clinical trials are needed to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Defibrotide for children and adults with hepatic veno-occlusive disease post hematopoietic cell transplantation.

PubMed

Corbacioglu, Selim; Richardson, Paul G

2017-10-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a complication that is typically associated with conditioning for hematopoietic stem cell transplantation (HSCT). In patients with concomitant multi-organ dysfunction, mortality may be >80%. Recently, the European Society for Blood and Marrow Transplantation established separate criteria for diagnosis and severity of VOD/SOS for adults and children, to better reflect current understanding of the disease. Areas covered: This review provides an overview of post-HSCT hepatic VOD/SOS and defibrotide, including its pharmacological, clinical, and regulatory profile. In children and adults following HSCT, defibrotide is approved for the treatment of hepatic VOD/SOS with concomitant renal or pulmonary dysfunction in the United States and for the treatment of severe hepatic VOD/SOS in the European Union. Day +100 survival rates with defibrotide are superior to those of historical controls receiving best supportive care only, and safety profiles are similar. Expert commentary: Defibrotide appears to act through multiple mechanisms to restore thrombo-fibrinolytic balance and protect endothelial cells, and there are promising data on the use of defibrotide for VOD/SOS prophylaxis in high-risk children undergoing HSCT. An ongoing randomized controlled trial in children and adults will better assess the clinical value of defibrotide as a preventive medication.

Experimental Evidences Supporting the Benefits of Exercise Training in Heart Failure.

PubMed

Ichige, Marcelo H A; Pereira, Marcelo G; Brum, Patrícia C; Michelini, Lisete C

2017-01-01

Heart Failure (HF), a common end point for many cardiovascular diseases, is a syndrome with a very poor prognosis. Although clinical trials in HF have achieved important outcomes in reducing mortality, little is known about functional mechanisms conditioning health improvement in HF patients. In parallel with clinical studies, basic science has been providing important discoveries to understand the mechanisms underlying the pathophysiology of HF, as well as to identify potential targets for the treatment of this syndrome. In spite of being the end-point of cardiovascular derangements caused by different etiologies, autonomic dysfunction, sympathetic hyperactivity, oxidative stress, inflammation and hormonal activation are common factors involved in the progression of this syndrome. Together these causal factors create a closed link between three important organs: brain, heart and the skeletal muscle. In the past few years, we and other groups have studied the beneficial effects of aerobic exercise training as a safe therapy to avoid the progression of HF. As summarized in this chapter, exercise training, a non-pharmacological tool without side effects, corrects most of the HF-induced neurohormonal and local dysfunctions within the brain, heart and skeletal muscles. These adaptive responses reverse oxidative stress, reduce inflammation, ameliorate neurohormonal control and improve both cardiovascular and skeletal muscle function, thus increasing the quality of life and reducing patients' morbimortality.

Blood Pressure, Sexual Activity, and Dysfunction in Women With Hypertension: Baseline Findings From the Systolic Blood Pressure Intervention Trial (SPRINT).

PubMed

Foy, Capri G; Newman, Jill C; Berlowitz, Dan R; Russell, Laurie P; Kimmel, Paul L; Wadley, Virginia G; Thomas, Holly N; Lerner, Alan J; Riley, William T

2016-09-01

Sexual function, an important component of quality of life, is gaining increased research and clinical attention in older women with hypertension. To assess the association between systolic blood pressure (SBP) and other variables, and sexual activity and sexual dysfunction in hypertensive women. Baseline analysis of 635 women participants of a larger randomized clinical trial of 9361 men and women. Self-reported sexual activity (yes/no), and sexual function using the Female Sexual Function Inventory (FSFI). 452 participants (71.2%) reported having no sexual activity during the previous 4 weeks. The mean (SD) FSFI score for sexually active participants was 25.3 (6.0), and 52.6% of the sample reported a FSFI score ≤26.55 designating sexual dysfunction. In logistic regression models, SBP was not significantly associated with sexual activity (AOR = 1.002; P > .05). Older age (AOR = 0.95, P < .05), and lower education (AOR for < high school vs college degree = 0.29, P < .05) were associated with lower odds of being sexually active, as was living alone versus living with others (AOR = 0.56, P < .05). Higher weekly alcohol consumption was associated with increased odds of being sexually active (AOR = 1.39; P < .05). In logistic regression models among sexually active participants, SBP was not associated with sexual dysfunction (AOR = 1.01; P > .05). Higher depressive symptoms from the Patient Health Questionnaire-9 (PHQ-9) was associated with higher odds of sexual dysfunction (AOR = 1.24, P < .05), as was increased number of physical comorbidities (AOR = 1.25, P < .05). Diuretic use was associated with lower odds of being sexually active in participants with chronic kidney disease (AOR = 0.33, P < .05). Younger age, higher education, living with others, and higher weekly alcohol consumption were significantly associated with higher odds of being sexually active in a sample of middle-aged and older women with hypertension. Increased depressive symptoms and increased physical comorbidities were significantly associated with increased odds of sexual dysfunction. SBP was not significantly associated with sexual activity or sexual dysfunction. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Association of low non-invasive near-infrared spectroscopic measurements during initial trauma resuscitation with future development of multiple organ dysfunction.

PubMed

Nicks, Bret A; Campons, Kevin M; Bozeman, William P

2015-01-01

Near-infrared spectroscopy (NIRS) non-invasively monitors muscle tissue oxygen saturation (StO2). It may provide a continuous noninvasive measurement to identify occult hypoperfusion, guide resuscitation, and predict the development of multiple organ dysfunction (MOD) after severe trauma. We evaluated the correlation between initial StO2 and the development of MOD in multi-trauma patients. Patients presenting to our urban, academic, Level I Trauma Center/Emergency Department and meeting standardized trauma-team activation criteria were enrolled in this prospective trial. NIRS monitoring was initiated immediately on arrival with collection of StO2 at the thenar eminence and continued up to 24 hours for those admitted to the Trauma Intensive Care Unit (TICU). Standardized resuscitation laboratory measures and clinical evaluation tools were collected. The primary outcome was the association between initial StO2 and the development of MOD within the first 24 hours based on a MOD score of 6 or greater. Descriptive statistical analyses were performed; numeric means, multivariate regression and rank sum comparisons were utilized. Clinicians were blinded from the StO2 values. Over a 14 month period, 78 patients were enrolled. Mean age was 40.9 years (SD 18.2), 84.4% were male, 76.9% had a blunt trauma mechanism and mean injury severity score (ISS) was 18.5 (SD 12.9). Of the 78 patients, 26 (33.3%) developed MOD within the first 24 hours. The MOD patients had mean initial StO2 values of 53.3 (SD 10.3), significantly lower than those of non-MOD patients 61.1 (SD 10.0); P=0.002. The mean ISS among MOD patients was 29.9 (SD 11.5), significantly higher than that of non-MODS patients, 12.1 (SD 9.1) (P<0.0001). The mean shock index (SI) among MOD patients was 0.92 (SD 0.28), also significantly higher than that of non-MODS patients, 0.73 (SD 0.19) (P=0.0007). Lactate values were not significantly different between groups. Non-invasive, continuous StO2 near-infrared spectroscopy values during initial trauma resuscitation correlate with the later development of multiple organ dysfunction in this patient population.

Dietary Nitrate Lowers Blood Pressure: Epidemiological, Pre-clinical Experimental and Clinical Trial Evidence.

PubMed

Gee, Lorna C; Ahluwalia, Amrita

2016-02-01

Nitric oxide (NO), a potent vasodilator critical in maintaining vascular homeostasis, can reduce blood pressure in vivo. Loss of constitutive NO generation, for example as a result of endothelial dysfunction, occurs in many pathological conditions, including hypertension, and contributes to disease pathology. Attempts to therapeutically deliver NO via organic nitrates (e.g. glyceryl trinitrate, GTN) to reduce blood pressure in hypertensives have been largely unsuccessful. However, in recent years inorganic (or 'dietary') nitrate has been identified as a potential solution for NO delivery through its sequential chemical reduction via the enterosalivary circuit. With dietary nitrate found in abundance in vegetables this review discusses epidemiological, pre-clinical and clinical data supporting the idea that dietary nitrate could represent a cheap and effective dietary intervention capable of reducing blood pressure and thereby improving cardiovascular health.

A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder

DTIC Science & Technology

2013-10-01

Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder PRINCIPAL INVESTIGATOR: John Gabrieli...SUBTITLE A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder 5a. CONTRACT NUMBER...dysfunctions and (2) oxytocin (OT) administration prior to CBT sessions will each enhance social function in young adults with autism spectrum disorders

Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse: case report and review of literature.

PubMed

Schäfer, C N; Guldager, H; Jørgensen, H L

2011-01-01

A 26-year-old male bodybuilder was admitted to the surgical department of a Danish community hospital for hematemesis. During the clinical interview, he revealed that he had recently finished a course of anabolic steroids and erythropoietin. The patient also had a previous history of infections and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency, and was transferred to the ICU. After manometric monitoring on the patient's upper arms proved difficult, invasive blood pressure monitoring was used and revealed that the patient was in a state of hypertensive crisis. This case of multi-organ dysfunction was possibly caused by multi-substance-induced hypercalcemia. © Georg Thieme Verlag KG Stuttgart · New York.

Infection Rate and Acute Organ Dysfunction Risk as Explanations for Racial Differences in Severe Sepsis

PubMed Central

Mayr, Florian B.; Yende, Sachin; Linde-Zwirble, Walter T.; Peck-Palmer, Octavia M.; Barnato, Amber E.; Weissfeld, Lisa A.; Angus, Derek C.

2013-01-01

Context Severe sepsis, defined as infection complicated by acute organ dysfunction, occurs more frequently and leads to more deaths in black than in white individuals. The optimal approach to minimize these disparities is unclear. Objective To determine the extent to which higher severe sepsis rates in black than in white patients are due to higher infection rates or to a higher risk of acute organ dysfunction. Design, Setting, and Participants Analysis of infection-related hospitalizations from the 2005 hospital discharge data of 7 US states and infection-related emergency department visits from the 2003-2007 National Hospital Ambulatory Care Survey. Main Outcome Measure Age- and sex-standardized severe sepsis and infection hospitalization rates and the risk of acute organ dysfunction. Results Of 8 661 227 non–childbirth-related discharges, 2 261 857 were associated with an infection, and of these, 381 787 (16.8%) had severe sepsis. Black patients had a 67% higher age- and sex-standardized severe sepsis rate than did white patients (9.4; 95% confidence interval [CI], 9.3-9.5 vs 5.6; 95% CI, 5.6-5.6 per 1000 population; P<.001) and 80% higher standardized mortality (1.8, 95% CI, 1.8-1.9 vs 1.0, 95% CI, 1.0-1.1 per 1000 population; P<.001). The higher severe sepsis rate was explained by both a higher infection rate in black patients (47.3; 95% CI, 47.1-47.4 vs 34.0; 95% CI, 33.9-34.0 per 1000 population; incidence rate ratio, 1.39; P<.001) and a higher risk of developing acute organ dysfunction (age- and sex-adjusted odds ratio [OR],1.29; 95% CI, 1.27-1.30; P<.001). Differences in infection presented broadly across different sites and etiology of infection and for community- and hospital-acquired infections and occurred despite a lower likelihood of being admitted for infection from the emergency department (adjusted OR, 0.70; 95% CI, 0.64-0.76; P<.001). The higher risk of organ dysfunction persisted but was attenuated after adjusting for age, sex, comorbid conditions, poverty, and hospital effect (OR, 1.14; 95% CI, 1.13-1.16; P<.001). Racial disparities in infection and severe sepsis incidence and mortality rates were largest among younger adults (eg, the proportion of invasive pneumococcal disease occurring in adults <65 years was 73.9% among black patients vs 44.5% among white patients, P<.001). Conclusion Racial differences in severe sepsis are explained by both a higher infection rate and a higher risk of acute organ dysfunction in black than in white individuals. PMID:20571016

A Randomized Trial Comparing Acupuncture, Simulated Acupuncture, and Usual Care for Chronic Low Back Pain

PubMed Central

Cherkin, Daniel C.; Sherman, Karen J.; Avins, Andrew L.; Erro, Janet H.; Ichikawa, Laura; Barlow, William E.; Delaney, Kristin; Hawkes, Rene; Hamilton, Luisa; Pressman, Alice; Khalsa, Partap S.; Deyo, Richard A.

2009-01-01

Background Acupuncture is a popular complementary and alternative treatment for chronic back pain. Recent European trials suggest similar short-term benefits from real and sham acupuncture needling. This trial addresses the importance of needle placement and skin penetration in eliciting acupuncture effects for patients with chronic low back pain. Methods 638 adults with chronic mechanical low back pain were randomized to: individualized acupuncture, standardized acupuncture, simulated acupuncture, or usual care. Ten treatments were provided over 7 weeks by experienced acupuncturists. The primary outcomes were back-related dysfunction (Roland Disability score, range: 0 to 23) and symptom bothersomeness (0 to 10 scale). Outcomes were assessed at baseline and after 8, 26 and 52 weeks. Results At 8 weeks, mean dysfunction scores for the individualized, standardized, and simulated acupuncture groups improved by 4.4, 4.5, and 4.4 points, respectively, compared with 2.1 points for those receiving usual care (P<0.001). Participants receiving real or simulated acupuncture were more likely than those receiving usual care to experience clinically meaningful improvements on the dysfunction scale (60% vs. 39%, P<0.0001). Symptoms improved by 1.6 to 1.9 points in the treatment groups compared with 0.7 points in the usual care group (P<0.0001). After one year, participants in the treatment groups were more likely than those receiving usual care group to experience clinically meaningful improvements in dysfunction (59% to 65% versus 50%, respectively, P=0.02) but not in symptoms (P>0.05). Conclusions Although acupuncture was found effective for chronic low back pain, tailoring needling sites to each patient and penetration of the skin appear to be unimportant in eliciting therapeutic benefits. These findings raise questions about acupuncture’s purported mechanisms of action. It remains unclear whether acupuncture, or our simulated method of acupuncture, provide physiologically important stimulation or represent placebo or non-specific effects. PMID:19433697

Toxic hepatitis in occupational exposure to solvents

PubMed Central

Malaguarnera, Giulia; Cataudella, Emanuela; Giordano, Maria; Nunnari, Giuseppe; Chisari, Giuseppe; Malaguarnera, Mariano

2012-01-01

The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. Work activities with hepatotoxins exposures are numerous and, moreover, organic solvents are used in various industrial processes. Organic solvents used in different industrial processes may be associated with hepatotoxicity. Several factors contribute to liver toxicity; among these are: species differences, nutritional condition, genetic factors, interaction with medications in use, alcohol abuse and interaction, and age. This review addresses the mechanisms of hepatotoxicity. The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. The health impact of exposure to solvents in the workplace remains an interesting and worrying question for professional health work. PMID:22719183

The Effects of a Low-Carbohydrate Diet vs. a Low-Fat Diet on Novel Cardiovascular Risk Factors: A Randomized Controlled Trial

PubMed Central

Hu, Tian; Yao, Lu; Reynolds, Kristi; Whelton, Paul K.; Niu, Tianhua; Li, Shengxu; He, Jiang; Bazzano, Lydia A.

2015-01-01

Increasing evidence supports a low-carbohydrate diet for weight loss and improvement in traditional cardiovascular disease (CVD) markers. Effects on novel CVD markers remain unclear. We examined the effects of a low-carbohydrate diet (<40 g/day; n = 75) versus a low-fat diet (<30% kcal/day from total fat, <7% saturated fat; n = 73) on biomarkers representing inflammation, adipocyte dysfunction, and endothelial dysfunction in a 12 month clinical trial among 148 obese adults free of diabetes and CVD. Participants met with a study dietitian on a periodic basis and each diet group received the same behavioral curriculum which included dietary instruction and supportive counseling. Eighty percent of participants completed the intervention. At 12 months, participants on the low-carbohydrate diet had significantly greater increases in adiponectin (mean difference in change, 1336 ng/mL (95% CI, 342 to 2330 ng/mL); p = 0.009) and greater decreases in intercellular adhesion molecule-1 concentrations (−16.8 ng/mL (−32.0 to −1.6 ng/mL); p = 0.031) than those on the low-fat diet. Changes in other novel CVD markers were not significantly different between groups. In conclusion, despite the differences in weight changes on diets, a low-carbohydrate diet resulted in similar or greater improvement in inflammation, adipocyte dysfunction, and endothelial dysfunction than a standard low-fat diet among obese persons. PMID:26393645

Rehabilitation of Executive Functions in Patients with Chronic Acquired Brain Injury with Goal Management Training, External Cuing, and Emotional Regulation: A Randomized Controlled Trial.

PubMed

Tornås, Sveinung; Løvstad, Marianne; Solbakk, Anne-Kristin; Evans, Jonathan; Endestad, Tor; Hol, Per Kristian; Schanke, Anne-Kristine; Stubberud, Jan

2016-04-01

Executive dysfunction is a common consequence of acquired brain injury (ABI), causing significant disability in daily life. This randomized controlled trial investigated the efficacy of Goal Management Training (GMT) in improving executive functioning in patients with chronic ABI. Seventy patients with a verified ABI and executive dysfunction were randomly allocated to GMT (n=33) or a psycho-educative active control condition, Brain Health Workshop (BHW) (n=37). In addition, all participants received external cueing by text messages. Neuropsychological tests and self-reported questionnaires of executive functioning were administered pre-intervention, immediately after intervention, and at 6 months follow-up. Assessors were blinded to group allocation. Questionnaire measures indicated significant improvement of everyday executive functioning in the GMT group, with effects lasting at least 6 months post-treatment. Both groups improved on the majority of the applied neuropsychological tests. However, improved performance on tests demanding executive attention was most prominent in the GMT group. The results indicate that GMT combined with external cueing is an effective metacognitive strategy training method, ameliorating executive dysfunction in daily life for patients with chronic ABI. The strongest effects were seen on self-report measures of executive functions 6 months post-treatment, suggesting that strategies learned in GMT were applied and consolidated in everyday life after the end of training. Furthermore, these findings show that executive dysfunction can be improved years after the ABI.

The effect of ursodeoxycholic acid in liver functional restoration of patients with obstructive jaundice after endoscopic treatment: a prospective, randomized, and controlled study.

PubMed

Fekaj, Enver; Gjata, Arben; Maxhuni, Mehmet

2013-09-22

In patients with obstructive jaundice, multi-organ dysfunction may develop. This trial is a prospective, open-label, randomized, and controlled study with the objective to evaluate the effect of ursodeoxycholic acid in liver functional restoration in patients with obstructive jaundice after endoscopic treatment. The aim of this study is to evaluate the effect of ursodeoxycholic acid in liver functional restoration of patients with obstructive jaundice after endoscopic treatment. The hypothesis of this trial is that patients with obstructive jaundice, in which will be administered UDCA, in the early phase after endoscopic intervention will have better and faster functional restoration of the liver than patients in the control group.Patients with obstructive jaundice, randomly, will be divided into two groups: (A) test group in which will be administered ursodeoxycholic acid twenty-four hours after endoscopic procedure and will last fourteen days, and (B) control group.Serum-testing will include determination of bilirubin, alanine transaminase, aspartate transaminase, gama-glutamil transpeptidase, alkaline phosphatase, albumin, and cholesterol levels. These parameters will be determined one day prior endoscopic procedure, and on the third, fifth, seventh, tenth, twelfth and fourteenth days after endoscopic intervention. This trial is a prospective, open-label, randomized, and controlled study to asses the effect of ursodeoxycholic acid in liver functional restoration of patients with obstructive jaundice in the early phase after endoscopic treatment.

Clinical response and mortality in tigecycline complicated intra-abdominal infection and complicated skin and soft-tissue infection trials.

PubMed

Bassetti, Matteo; McGovern, Paul C; Wenisch, Christoph; Meyer, R Daniel; Yan, Jean Li; Wible, Michele; Rottinghaus, Scott T; Quintana, Alvaro

2015-09-01

An imbalance in all-cause mortality was noted in tigecycline phase 3 and 4 comparative clinical trials across all studied indications. We investigated clinical failure and mortality in phase 3 and 4 complicated skin and soft-tissue infection (cSSTI) and complicated intra-abdominal infection (cIAI) tigecycline trials using descriptive analyses of a blinded adjudication of mortality and multivariate regression analyses. Attributable mortality analyses of cSSTI revealed death due to infection in 0.1% of each treatment group (P=1.000). In cIAI, there were no significant differences between tigecycline (1.2%) and comparator (0.7%) subjects who died due to infection (P=0.243). For cIAI clinical failure, treatment interaction with organ dysfunction was observed with no difference observed between clinical cure for tigecycline (85.4%) and comparator (76.7%) treatment groups (odds ratio=0.58, 95% confidence interval 0.28-1.19). Tigecycline-treated subjects had more adverse events of secondary pneumonias (2.1% vs. 1.2%) and more adverse events of secondary pneumonias with an outcome of death (0.5% vs. 0.1%). These analyses do not suggest that tigecycline is a factor either for failure (cSSTI and cIAI studies) or for death (cIAI studies). Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

The Effects of Laughter Therapy on General Health of Elderly People Referring to Jahandidegan Community Center in Shiraz, Iran, 2014: A Randomized Controlled Trial

PubMed Central

Ghodsbin, Fariba; Sharif Ahmadi, Zahra; Jahanbin, Iran; Sharif, Farkhondeh

2015-01-01

Background: Aging and its social-biological process naturally impair the functions of different body organs and cause progressive disabilities in managing personal affairs and performing social roles. Laughter therapy is an important strategy which has been recommended by experts for increasing health promotion in older adults. Therefore, we aimed to investigate the effect of laughter therapy program on public health of senior citizens. Methods: In a randomized controlled trial, we enrolled 72 senior citizens aged 60 and over referring to Jahandidegan (Khold-e-Barin) retirement community center in Shiraz, southwest Iran during January to February 2014. The participants were assigned into experimental (N=36) and control (N=36) groups. Data were collected using General Health Questionnaire (GHQ-28) and demographic questionnaire. The participants of experimental group attended a laughter therapy program consisting of two 90-minute sessions per week lasting for 6 weeks. Results: We found a statistically significant correlation between laughter therapy program and factors such as general health (P=0.001), somatic symptoms (P=0.001), insomnia and anxiety (P=0.001). However, there was no statistically significant correlation among laughter therapy, social dysfunction (P=0.28) and depression (P=0.069). Conclusion: We concluded that laughter therapy can improve general health and its subscales in elderly people. Trial Registration Number: IRCT2014061111691N4 PMID:25553332

Magnetic resonance imaging of pelvic floor dysfunction.

PubMed

Lalwani, Neeraj; Moshiri, Mariam; Lee, Jean H; Bhargava, Puneet; Dighe, Manjiri K

2013-11-01

Pelvic floor dysfunction is largely a complex problem of multiparous and postmenopausal women and is associated with pelvic floor or organ descent. Physical examination can underestimate the extent of the dysfunction and misdiagnose the disorders. Functional magnetic resonance (MR) imaging is emerging as a promising tool to evaluate the dynamics of the pelvic floor and use for surgical triage and operative planning. This article reviews the anatomy and pathology of pelvic floor dysfunction, typical imaging findings, and the current role of functional MR imaging. Copyright © 2013 Elsevier Inc. All rights reserved.

Hepatic dysfunction.

PubMed

McCord, Kelly W; Webb, Craig B

2011-07-01

This article reviews the common pathophysiology that constitutes hepatic dysfunction, regardless of the inciting cause. The systemic consequences of liver failure and the impact of this condition on other organ systems are highlighted. The diagnostic tests available for determining the cause and extent of liver dysfunction are outlined, treatment strategies aimed at supporting hepatic health and recovery are discussed, and prognosis is briefly covered. The article emphasizes the fact that because of the central role of the liver in maintaining normal systemic homeostasis, hepatic dysfunction cannot be effectively addressed as an isolated entity. Copyright © 2011 Elsevier Inc. All rights reserved.

Extracorporeal shock wave therapy (ESWT) in urology: a systematic review of outcome in Peyronie's disease, erectile dysfunction and chronic pelvic pain.

PubMed

Fojecki, Grzegorz Lukasz; Tiessen, Stefan; Osther, Palle Jörn Sloth

2017-01-01

The objective was to evaluate high-level evidence studies of extracorporeal shock wave therapy (ESWT) for urological disorders. We included randomized controlled trials reporting outcomes of ESWT in urology. Literature search on trials published in English using EMBASE, Medline and PubMed was carried out. The systematic review was performed according to PRISMA guidelines. We identified 10 trials on 3 urological indications. Two of 3 trials on Peyronie's disease (PD) involving 238 patients reported improvement in pain; however, no clinical significant changes in penile deviation and plaque size were observed. Four studies on erectile dysfunction (ED) including 337 participants were included. Using International Index of Erectile Function (IIEF-EF) and erectile hardness scale (EHS) data suggested a significant positive effect of ESWT in phosphodiesterase-5 inhibitor (PDE-5i) responders in 2 of 4 trials and 3 of 4 trials, respectively. Three studies on chronic pelvic pain (CPP) engaging 200 men reported positive changes in National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). There was considerable heterogeneity between trials both with regard to treatment techniques and outcome measures, making it difficult to compare results. ESWT may resolve pain in PD patients, while evidence for reducing curvature and plaques size is poor. Effects of ESWT on IIEF in ED patients are inconsistent; however, data on EHS does imply that the treatment potentially may recover natural erection in PDE-5i responders. ESWT seems to be able to resolve pain in CPP patients in the short term. In all three disease entities, long-term outcome data are still warranted.

[Successful continuous renal replacement therapy in a neonate with early-onset group B streptococcal sepsis and multi-organ dysfunction syndrome].

PubMed

von Schnakenburg, C; Hufnagel, M; Superti-Furga, A; Rieger-Fackeldey, E; Berner, R

2009-01-01

Group B streptococcal early-onset sepsis (GBS EOS) in neonates has a mortality rate of approximately 5%, particularly in the presence of multi-organ dysfunction. Fluid management is crucial in these patients, and continuous venovenous haemofiltration (CVVH) should be considered a therapeutic option even in newborn babies. After an uneventful pregnancy within hours after birth, a female term infant presented with dyspnoea, irritability and cyanosis. The systemic inflammatory response syndrome (SIRS) progressed to multi-organ dysfunction with acute respiratory distress syndrome (ARDS), impaired myocardial contractility, pulmonary hypertension and fluid overload. The maximum PRISM score was 51. The child required maximal respiratory and inotropic support with high volume intravenous fluid administration. However, only by using of CVVH from day 5 to 14, we successfully resolved progressive pulmonary and cardiovascular dysfunction. The child improved directly after initiation of fluid removal, was extubated on day 17 and discharged without obvious sequelae on day 57. All microbiology studies revealed GBS. Perinatal GBS-infections remain a major life-threatening event for newborn babies. CVVH should be considered an option for reversing fluid overload even in neonates with overwhelming SIRS. Alternatively, extracorporeal membrane oxygenation (ECMO) is discussed.

Quality of life in preoperative patients with sacroiliac joint dysfunction is at least as depressed as in other lumbar spinal conditions.

PubMed

Cher, Daniel Joseph; Reckling, W Carlton

2015-01-01

Pain from the sacroiliac joint (SIJ) is an under-recognized cause of low back pain. The degree to which SIJ pain decreases quality of life has not been directly compared to other more familiar conditions of the lumbar spine. Multivariate regression analysis of individual patient data from two prospective multicenter clinical trials of SIJ fusion and three prospective multicenter clinical trials of surgical treatments for degenerative lumbar spine conditions. Controlling for baseline demographic parameters as well as a validated disability score, quality of life scores (EuroQOL 5-D and SF-36) were, in most cases, lower in the SIJ cohorts compared to the three other spine surgery cohorts. Patients with SIJ dysfunction considering surgery have decrements in quality of life as or more severe compared to patients with degenerative spondylolisthesis, spinal stenosis, and intervertebral disc herniation.

Effect of the peels of two Citrus fruits on endothelium function in adolescents with excess weight: A triple-masked randomized trial.

PubMed

Hashemi, Mohammad; Khosravi, Elham; Ghannadi, Alireza; Hashemipour, Mahin; Kelishadi, Roya

2015-08-01

Obesity induces endothelial dysfunction even in the pediatric age group. The possible protective effects of fruits and herbal products on the endothelial dysfunction of obese children remain to be determined. This study aims to investigate the effects of lemon and sour orange peels on endothelial function of adolescents with excess weight. This triple-masked, randomized placebo-controlled trial was conducted for 1-month among 90 overweight and obese participants, aged 6-18 years. They were randomly assigned into three groups of equal number receiving daily oral capsules containing lemon or sour orange powder or placebo. Flow-mediated dilatation (FMD) was compared between three groups by using analysis of covariance. Overall, 30 participants in the lemon group, 27 in the sour orange group and 29 in the control group completed the trial. After the trial, mean FMD was significantly (P < 0.001) higher in the lemon group (11.99 ± 4.05) and in the sour orange group (12.79 ± 5.47) than in the placebo group (6.45 ± 2.79). FMD percent change was 145.02 ± 24.34 in the lemon group, 142.04 ± 16.11 in the sour orange group, and 46.73 ± 5.16 in controls (P < 0.001). This trial showed that consumption of extracts of lemon and sour orange peels, which contain plenty amounts of antioxidants, flavonoids, pectin, and vitamin C, might have significant benefits on endothelial function in children and adolescents with excess weight. Trial registry code: IRCT201311201434N10.

Case report: severe heat stroke with multiple organ dysfunction – a novel intravascular treatment approach

PubMed Central

Broessner, Gregor; Beer, Ronny; Franz, Gerhard; Lackner, Peter; Engelhardt, Klaus; Brenneis, Christian; Pfausler, Bettina; Schmutzhard, Erich

2005-01-01

Introduction We report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia. Methods A 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia. Results Analyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard® and CoolLine®) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke. Conclusion In this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result. PMID:16285034

Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies.

PubMed

Palma, Jose-Alberto; Kaufmann, Horacio

2018-03-01

Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully. Discontinuation of potentially causative/aggravating drugs, patient education, and nonpharmacological approaches are useful and should be tried first. Pathophysiology-based pharmacological treatments that have shown efficacy in controlled trials of patients with synucleinopathies have been approved in many countries and are key to an effective management. Here, we review the treatment of autonomic dysfunction in patients with Parkinson disease and other synucleinopathies, summarize the nonpharmacological and current pharmacological therapeutic strategies including recently approved drugs, and provide practical advice and management algorithms for clinicians, with focus on neurogenic orthostatic hypotension, supine hypertension, dysphagia, sialorrhea, gastroparesis, constipation, neurogenic overactive bladder, underactive bladder, and sexual dysfunction. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Targeting IL-2: an unexpected effect in treating immunological diseases.

PubMed

Ye, Congxiu; Brand, David; Zheng, Song G

2018-01-01

Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis since Treg dysfunction in both animals and humans is associated with multi-organ autoimmune and inflammatory disease. While IL-2 is generally considered to promote T-cell proliferation and enhance effector T-cell function, recent studies have demonstrated that treatments that utilize low-dose IL-2 unexpectedly induce immune tolerance and promote Treg development resulting in the suppression of unwanted immune responses and eventually leading to treatment of some autoimmune disorders. In the present review, we discuss the biology of IL-2 and its signaling to help define the key role played by IL-2 in the development and function of Treg cells. We also summarize proof-of-concept clinical trials which have shown that low-dose IL-2 can control autoimmune diseases safely and effectively by specifically expanding and activating Treg. However, future studies will be needed to validate a better and safer dosing strategy for low-dose IL-2 treatments utilizing well-controlled clinical trials. More studies will also be needed to validate the appropriate dose of IL-2/anti-cytokine or IL-2/anti-IL-2 complex in the experimental animal models before moving to the clinic.

The Cardio-Renal Interrelationship.

PubMed

Boudoulas, Konstantinos Dean; Triposkiadis, Filippos; Parissis, John; Butler, Javed; Boudoulas, Harisios

The heart and the kidney are of utmost importance for the maintenance of cardiovascular (CV) homeostasis. In healthy subjects, hemodynamic changes in either organ may affect hemodynamics of the other organ. This interaction is fine-tuned by neurohumoral activity, including atrial natriuretic peptides, renin-angiotensin aldosterone system and sympathetic activity. Dysfunction or disease of one organ may initiate, accentuate, or precipitate dysfunction or disease state in the other organ, often leading to a vicious cycle. Further, the interaction between the heart and the kidney may occur in the setting of processes and diseases that may affect both organs simultaneously, such as advanced age, hypertension, diabetes mellitus, atherosclerosis, etc. In this regard, a stiff aorta that occurs with aging due to mechanical stress may independently initiate or precipitate dysfunction and disease in the heart and the kidney. All of these factors contribute to a high prevalence of coexistent CV and kidney disease, especially in the elderly. In advanced kidney disease, hemodynamic and neurohumoral homeostasis are lost, volume and pressure overload may coexist, and the elimination of certain pharmacologic agents may be substantially impaired. Thus, coexistence of CV and kidney disease complicates diagnosis, propagates pathophysiology, adversely affects prognosis, and hinders management. Copyright © 2016 Elsevier Inc. All rights reserved.

The efficacy of treadmill training on balance dysfunction in individuals with chronic stroke: a systematic review.

PubMed

Tally, Zachary; Boetefuer, Laura; Kauk, Courtney; Perez, Gabriela; Schrand, Lorraine; Hoder, Jeffrey

2017-10-01

Physical activity and exercise interventions are useful in facilitating the functional recovery of those with chronic stroke and, routinely, are gait-specific. While treadmill training has proven useful in gait performance recovery post-stroke, its efficacy on balance dysfunction has not been  systematically reviewed. The purpose of this systematic review was to determine the effect of treadmill training (TT) interventions on balance dysfunction in individuals with chronic stroke. A systematic literature search of PubMed, EMBASE, and CINAHL was performed. Eligible randomized controlled trials were published between 2007 and 2016. Selected trials investigated TT interventions in persons with chronic stroke and implemented at least one objective balance measure. Methodological quality was assessed using PEDro criteria. Eight studies met eligibility criteria and were included in the qualitative analysis. Studies differed in TT implementation and use of adjunctive treatments; however, all trials demonstrated improvements in balance measures that were as effective, if not more so, than conventional physical therapy treatments, including targeted balance training. This review recognized moderate evidence in favor of TT interventions in balance and stroke rehabilitation programs. With TT, intensity may be a more critical factor than specificity and may offer additional carryover to recovery parameters of postural control and balance, beyond gait performance. It is recommended that clinicians utilizing TT incorporate objective measures of balance to assess the potential for skill transference and improvements in balance. Higher quality studies and additional research are needed to denote critical parameters by which improvements in balance may be optimized.

Using gene chips to identify organ-specific, smooth muscle responses to experimental diabetes: potential applications to urological diseases.

PubMed

Hipp, Jason D; Davies, Kelvin P; Tar, Moses; Valcic, Mira; Knoll, Abraham; Melman, Arnold; Christ, George J

2007-02-01

To identify early diabetes-related alterations in gene expression in bladder and erectile tissue that would provide novel diagnostic and therapeutic treatment targets to prevent, delay or ameliorate the ensuing bladder and erectile dysfunction. The RG-U34A rat GeneChip (Affymetrix Inc., Sunnyvale, CA, USA) oligonucleotide microarray (containing approximately 8799 genes) was used to evaluate gene expression in corporal and male bladder tissue excised from rats 1 week after confirmation of a diabetic state, but before demonstrable changes in organ function in vivo. A conservative analytical approach was used to detect alterations in gene expression, and gene ontology (GO) classifications were used to identify biological themes/pathways involved in the aetiology of the organ dysfunction. In all, 320 and 313 genes were differentially expressed in bladder and corporal tissue, respectively. GO analysis in bladder tissue showed prominent increases in biological pathways involved in cell proliferation, metabolism, actin cytoskeleton and myosin, as well as decreases in cell motility, and regulation of muscle contraction. GO analysis in corpora showed increases in pathways related to ion channel transport and ion channel activity, while there were decreases in collagen I and actin genes. The changes in gene expression in these initial experiments are consistent with the pathophysiological characteristics of the bladder and erectile dysfunction seen later in the diabetic disease process. Thus, the observed changes in gene expression might be harbingers or biomarkers of impending organ dysfunction, and could provide useful diagnostic and therapeutic targets for a variety of progressive urological diseases/conditions (i.e. lower urinary tract symptoms related to benign prostatic hyperplasia, erectile dysfunction, etc.).

Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in critical illness including sepsis and septic shock: relation to disease severity, multiple organ dysfunction, and mortality.

PubMed

Presneill, J J; Waring, P M; Layton, J E; Maher, D W; Cebon, J; Harley, N S; Wilson, J W; Cade, J F

2000-07-01

To define the circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during critical illness and to determine their relationship to the severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the development of multiple organ dysfunction, or mortality. Prospective cohort study. University hospital intensive care unit. A total of 82 critically ill adult patients in four clinically defined groups, namely septic shock (n = 29), sepsis without shock (n = 17), shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14). None. During day 1 of septic shock, peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and were correlated among themselves (rs = 0.44-0.77; p < .02) and with the APACHE II score (rs = 0.25-0.40; p = .03 to .18). G-CSF, IL-6, and UF, and sepsis, shock, septic shock, and APACHE II scores were strongly associated with organ dysfunction or 5-day mortality by univariate analysis. However, multiple logistic regression analysis showed that only septic shock remained significantly associated with organ dysfunction and only APACHE II scores and shock with 5-day mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day mortality. Plasma levels of G-CSF, IL-6, and LIF are greatly elevated in critical illness, including septic shock, and are correlated with one another and with the severity of illness. However, they are not independently predictive of mortality, or the development of multiple organ dysfunction. GM-CSF was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human septic shock.

Adjuvant treatment with crude rhubarb for patients with acute organophosphorus pesticide poisoning: A meta-analysis of randomized controlled trials.

PubMed

Wang, Lina; Pan, Shuming

2015-12-01

Crude rhubarb has been used to treat critically ill patients for many years. However, no previous meta-analysis has been investigated the benefits of crude rhubarb in patients with acute organophosphorus pesticide poisoning (AOPP). To summarize the beneficial effects of adjuvant treatment with crude rhubarb in patients with AOPP by conducting a meta-analysis. A literature search of the databases through Pubmed, EMBASE, China National Knowledge Infrastructure, VIP, and Wanfang were performed for studies published up to October 2014. Randomized controlled trials (RCTs) investigating the effects of crude rhubarb as adjuvant treatment for patients with AOPP were included. A total of 12 RCTs with 886 patients were identified. Adjuvant treatment with crude rhubarb was associated with a significantly lower incidence of intermediate syndrome (risk ratio [RR] 0.22; 95% confidence interval [CI] 0.10-0.48), as well as multiple organ dysfunction syndrome (RR 0.34; 95% CI 0.20-0.56). Crude rhubarb as adjuvant treatment reduced the total dose of pralidoxime (mean difference [MD] -5.12 g; 95% CI -8.24 to -2.00) or atropine (MD -94.89 mg; 95% CI -156.22 to -33.57), and hospital length of stay (MD -2.79 days; 95% CI -4.19 to -1.39) compared with the controls. This meta-analysis suggests that crude rhubarb as adjuvant treatment appears to have additional beneficial effects in patients with AOPP. More well-designed trials are needed to confirm our findings due to the methodological flaws of the included trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exposure to volatile organic compounds and kidney dysfunction in thin film transistor liquid crystal display (TFT-LCD) workers.

PubMed

Chang, Ta-Yuan; Huang, Kuei-Hung; Liu, Chiu-Shong; Shie, Ruei-Hao; Chao, Keh-Ping; Hsu, Wen-Hsin; Bao, Bo-Ying

2010-06-15

Many volatile organic compounds (VOCs) are emitted during the manufacturing of thin film transistor liquid crystal displays (TFT-LCDs), exposure to some of which has been reported to be associated with kidney dysfunction, but whether such an effect exists in TFT-LCD industry workers is unknown. This cross-sectional study aimed to investigate the association between exposure to VOCs and kidney dysfunction among TFT-LCD workers. The results showed that ethanol (1811.0+/-1740.4 ppb), acetone (669.0+/-561.0 ppb), isopropyl alcohol (187.0+/-205.3 ppb) and propylene glycol monomethyl ether acetate (PGMEA) (102.9+/-102.0 ppb) were the four dominant VOCs present in the workplace. The 63 array workers studied had a risk of kidney dysfunction 3.21-fold and 3.84-fold that of 61 cell workers and 18 module workers, respectively. Workers cumulatively exposed to a total level of isopropyl alcohol, PGMEA and propylene glycol monomethyl ether> or =324 ppb-year had a significantly higher risk of kidney dysfunction (adjusted OR=3.41, 95% CI=1.14-10.17) compared with those exposed to <25 ppb-year after adjustment for potential confounding factors. These findings indicated that array workers might be the group at greatest risk of kidney dysfunction within the TFT-LCD industry, and cumulative exposure to specific VOCs might be associated with kidney dysfunction. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

Endotoxemia Following Multiple Trauma: Risk Factors and Prognostic Implications.

PubMed

Charbonney, Emmanuel; Tsang, Jennifer Y; Li, Yangmei; Klein, David; Duque, Patricia; Romaschin, Alexander; Marshall, John C

2016-02-01

To evaluate the prevalence and time course of systemic endotoxemia following severe multiple trauma, to define its risk factors, and to explore the correlation between post-trauma endotoxemia and organ dysfunction. Prospective single-center cohort study. Emergency department and ICU of adult tertiary care level I trauma center. Forty-eight severely injured (Injury Severity Score ≥ 16) patients, admitted to ICU within 24 hours of injury. None. Endotoxemia was not evident on initial presentation, but developed subsequently in 75% of patients, even in the absence of Gram-negative infection. Nonsurviving patients had higher endotoxin levels than survivors on day 1 (endotoxemia, 0.48 vs 0.28; p = 0.048). Shock at admission, or surgery within the first 48 hours after trauma, was associated with higher endotoxin levels and predicted subsequent maximal endotoxemia, after adjusting for other significant covariates. Maximal endotoxemia levels were higher in patients who developed organ dysfunction, reflected in a cumulative Multiple Organ Dysfunction Score greater than 25, and patients with an intermediate endotoxemia level (≥ 0.4) had more cardiovascular dysfunction. It is the first study to detect increasing levels of endotoxemia following multiple trauma. Shock and early surgery predict the development of endotoxemia; endotoxemia is particularly associated with cardiovascular dysfunction. However, Gram-negative infections are uncommon in these patients, suggesting that the gastrointestinal tract is the dominant reservoir of endotoxin. Endotoxin may be an appropriate therapeutic target in patients who have sustained severe multiple trauma.

Management of fever, hyperglycemia, and swallowing dysfunction following hospital admission for acute stroke in New South Wales, Australia.

PubMed

Drury, Peta; Levi, Christopher; McInnes, Elizabeth; Hardy, Jennifer; Ward, Jeanette; Grimshaw, Jeremy M; D' Este, Catherine; Dale, Simeon; McElduff, Patrick; Cheung, N Wah; Quinn, Clare; Griffiths, Rhonda; Evans, Malcolm; Cadilhac, Dominique; Middleton, Sandy

2014-01-01

Fever, hyperglycemia, and swallow dysfunction poststroke are associated with significantly worse outcomes. We report treatment and monitoring practices for these three items from a cohort of acute stroke patients prior to randomization in the Quality in Acute Stroke Care trial. Retrospective medical record audits were undertaken for prospective patients from 19 stroke units. For the first three-days following stroke, we recorded all temperature readings and administration of paracetamol for fever (≥37·5°C) and all glucose readings and administration of insulin for hyperglycemia (>11 mmol/L). We also recorded swallow screening and assessment during the first 24 h of admission. Data for 718 (98%) patients were available; 138 (19%) had four hourly or more temperature readings and 204 patients (29%) had a fever, with 44 (22%) receiving paracetamol. A quarter of patients (n = 102/412, 25%) had six hourly or more glucose readings and 23% (95/412) had hyperglycemia, with 31% (29/95) of these treated with insulin. The majority of patients received a swallow assessment (n = 562, 78%) by a speech pathologist in the first instance rather than a swallow screen by a nonspeech pathologist (n = 156, 22%). Of those who passed a screen (n = 108 of 156, 69%), 68% (n = 73) were reassessed by a speech pathologist and 97% (n = 71) were reconfirmed to be able to swallow safely. Our results showed that acute stroke patients were: undermonitored and undertreated for fever and hyperglycemia; and underscreened for swallowing dysfunction and unnecessarily reassessed by a speech pathologist, indicating the need for urgent behavior change. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Change in Dysfunctional Beliefs About Sleep in Behavior Therapy, Cognitive Therapy, and Cognitive-Behavioral Therapy for Insomnia.

PubMed

Eidelman, Polina; Talbot, Lisa; Ivers, Hans; Bélanger, Lynda; Morin, Charles M; Harvey, Allison G

2016-01-01

As part of a larger randomized controlled trial, 188 participants were randomized to behavior therapy (BT), cognitive therapy (CT), or cognitive-behavioral therapy (CBT) for insomnia. The aims of this study were threefold: (a) to determine whether change in dysfunctional beliefs about sleep was related to change in sleep, insomnia symptoms, and impairment following treatment; (b) to determine whether BT, CT, and CBT differ in their effects on dysfunctional beliefs; and (c) to determine whether the treatments differ in their effects on particular kinds of dysfunctional beliefs. Beliefs, sleep, insomnia symptoms, and sleep-related psychosocial impairment were assessed at pretreatment, posttreatment, and 6- and 12-month follow-up. Greater change in dysfunctional beliefs occurring over the course of BT, CT, or CBT was associated with greater improvement in insomnia symptoms and impairment at posttreatment and both follow-ups. All groups experienced a significant decrease in dysfunctional beliefs during treatment, which were sustained through 6- and 12-month follow-up. Compared with the BT group, a greater proportion of participants in the CT and/or CBT groups endorsed dysfunctional beliefs below a level considered clinically significant at posttreatment and 12-month follow-up. The results demonstrate the importance of targeting dysfunctional beliefs in insomnia treatment, suggest that beliefs may be significantly modified with BT alone, and indicate that cognitive interventions may be particularly powerful in enhancing belief change. Copyright © 2016. Published by Elsevier Ltd.

Cardio-renal syndromes: from foggy bottoms to sunny hills.

PubMed

Ronco, Claudio

2011-11-01

"Cardio-renal syndromes" (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.

Candidate Dosimetric Predictors of Long-Term Swallowing Dysfunction After Oropharyngeal Intensity-Modulated Radiotherapy

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

Schwartz, David L., E-mail: docdls@mdanderson.or; Department of Experimental Diagnostic Imaging, University of Texas M. D. Anderson Cancer Center, Houston, TX; Hutcheson, Katherine

2010-12-01

Purpose: To investigate long-term swallowing function in oropharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT), and to identify novel dose-limiting criteria predictive for dysphagia. Methods and Materials: Thirty-one patients with Stage IV oropharyngeal squamous carcinoma enrolled on a Phase II trial were prospectively evaluated by modified barium swallow studies at baseline, and 6, 12, and 24 months post-IMRT treatment. Candidate dysphagia-associated organs at risk were retrospectively contoured into original treatment plans. Twenty-one (68%) cases were base of tongue and 10 (32%) were tonsil. Stage distribution was T1 (12 patients), T2 (10), T3 (4), T4 (2), and TX (3), and N2more » (24), N3 (5), and NX (2). Median age was 52.8 years (range, 42-78 years). Thirteen patients (42%) received concurrent chemotherapy during IMRT. Thirteen (42%) were former smokers. Mean dose to glottic larynx for the cohort was limited to 18 Gy (range, 6-39 Gy) by matching IMRT to conventional low-neck fields. Results: Dose-volume constraints (V30 < 65% and V35 < 35% for anterior oral cavity and V55 < 80% and V65 < 30% for high superior pharyngeal constrictors) predictive for objective swallowing dysfunction were identified by univariate and multivariate analyses. Aspiration and feeding tube dependence were observed in only 1 patient at 24 months. Conclusions: In the context of glottic laryngeal shielding, we describe candidate oral cavity and superior pharyngeal constrictor organs at risk and dose-volume constraints associated with preserved long-term swallowing function; these constraints are currently undergoing prospective validation. Strict protection of the glottic larynx via beam-split IMRT techniques promises to make chronic aspiration an uncommon outcome.« less

Performance assessment model for guideline-recommended pharmacotherapy in the secondary prevention of coronary artery disease and treatment of left ventricular dysfunction.

PubMed

Simpson, R J; Sueta, C A; Boccuzzi, S J; Lulla, A; Biggs, D; Londhe, A; Smith, S C

1997-10-30

The Agency for Health Care Policy and Research, the National Heart Lung and Blood Institute of the National Institutes of Health, the American Heart Association, and the American College of Cardiology have all developed guidelines for improving the care of patients with cardiovascular disease. The guidelines include recommendations for intensive lipid-lowering therapy in patients with coronary artery disease (CAD) and angiotensin-converting enzyme (ACE) inhibitors in those patients with symptomatic heart failure and asymptomatic left ventricular dysfunction. Despite clinical trial evidence and consensus that these therapies improve survival in high-risk patients, data suggest that there is wide variation in the delivery of guideline-based care. To investigate whether evidence-based assessment of provider practice patterns can impact the delivery of quality cost-effective care, Merck and Company, in conjunction with leading cardiology group practices, the University of North Carolina at Chapel Hill, and Medical Review of North Carolina developed an ambulatory medical record abstraction study. This quality assurance initiative was conducted at practices beginning in the spring of 1996 and continues. Medical records and administrative claims of patients with ischemic heart disease or heart failure were abstracted by a healthcare consulting organization to maintain patient and physician confidentiality. As of mid-July 1997, 626 group practices had completed the medical record abstraction process, with > 1,136 practices participating at some stage of the project; >6,000 physicians participated in the project and >270,000 patients charts were abstracted. Analysis of these data will provide insight and benchmark patterns of care in the pharmacologic management of heart failure and CAD. This project represents a unique collaboration between a pharmaceutical company, an academic institution, a Peer Review Organization, and practicing physicians, to support evidence-based best medical practices.

Impact of pelvic floor muscle training on sexual function of women with urinary incontinence and a comparison of electrical stimulation versus standard treatment (IPSU trial): a randomised controlled trial.

PubMed

Jha, Swati; Walters, Stephen J; Bortolami, Oscar; Dixon, Simon; Alshreef, Abualbishr

2018-03-01

To evaluate the clinical and cost-effectiveness of electric stimulation plus standard pelvic floor muscle training compared to standard pelvic floor muscle training alone in women with urinary incontinence and sexual dysfunction. Single centre two arm parallel group randomised controlled trial conducted in a Teaching hospital in England. Participants were women presenting with urinary incontinence and sexual dysfunction. The interventions compared were electric stimulation versus standard pelvic floor muscle training. included Prolapse and Incontinence Sexual function Questionnaire (PISQ) physical function dimension at post-treatment (primary); other dimensions of PISQ, SF-36; EQ-5D, EPAQ, resource use, adverse events and cost-effectiveness (secondary outcomes). 114 women were randomised (Intervention n=57; Control group n=57). 64/114 (56%). had valid primary outcome data at follow-up (Intervention 30; Control 34). The mean PISQ-PF dimension scores at follow-up were 33.1 (SD 5.5) and 32.3 (SD 5.2) for the Intervention and Control groups respectively; with the Control group having a higher (better) score. After adjusting for baseline score, BMI, menopausal status, time from randomisation and baseline oxford scale score the mean difference was -1.0 (95% CI: -4.0 to 1.9; P=0.474). There was no differences between the groups in any of the secondary outcomes at follow-up. Within this study, the use of electrical stimulation was cost-effective with very small incremental costs and quality adjusted life years (QALYs). In women presenting with urinary incontinence in conjunction with sexual dysfunction, physiotherapy is beneficial to improve overall sexual function. However no specific form of physiotherapy is beneficial over another. Trial registration ISRCTN09586238. Copyright © 2017 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Beta-Blockers (Carvedilol) in Children with Systemic Ventricle Systolic Dysfunction - Systematic Review and Meta-Analysis.

PubMed

Prijic, Sergej; Buchhorn, Reiner; Kosutic, Jovan; Vukomanovic, Vladislav; Prijic, Andreja; Bjelakovic, Bojko; Zdravkovic, Marija

2014-01-01

Numerous prospective randomized clinical trials demonstrated favorable effect of beta-blockers in adults with chronic heart failure. However, effectiveness of beta blockers in pediatric patients with systemic ventricle systolic dysfunction was not recognized sufficiently. Limited number of pediatric patients might be the course of unrecognized carvediolol treatment benefit. Currently, no meta-analysis has examined the impact of carvedilol and conventional therapy on the clinical outcome in children with chronic heart failure due to impaired systemic ventricle systolic function. We have systematically searched the Medline/PubMed and Cochrane Library for the controlled clinical trials that examine carvedilol and standard treatment efficacy in pediatric patients with systemic ventricle systolic dysfunction. Mean differences for continuous variables, odds ratios for dichotomous outcomes, heterogeneity between studies and publication bias were calculated using Cochrane Review Manager (Rev Man 5.2). Total of 8 prospective/observational studies met established criteria. Odds ratio for chronic heart failure related mortality/heart transplantation secondary to carvedilol was 0.52 (95% CI: 0.28-0.97, I(2) = 0%). Our analysis showed that carvedilol could prevent 1 death/ heart transplantation by treating 14 pediatric patients with impaired systemic ventricle systolic function. Meta-analysis demonstrated clinical outcome benefit of carvedilol in children with chronic heart failure.

The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction - baseline characteristics of the study population.

PubMed

Ferrari, R; Ford, I; Fox, K; Steg, P G; Tendera, M

2008-01-01

Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline. BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%). A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%). Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients. (c) 2007 S. Karger AG, Basel

Endocannabinoid system dysfunction in mood and related disorders.

PubMed

Ashton, C H; Moore, P B

2011-10-01

The endocannabinoid (EC) system is widely distributed throughout the brain and modulates many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. This article examines the therapeutic potential of cannabinoids in psychiatric disorders. An overview is presented of the literature focussed on the functions of the EC system, its dysfunction in mood disorders and the therapeutic potential of exogenous cannabinoids. We propose (hypothesize) that the EC system, which is homoeostatic in cortical excitation and inhibition, is dysfunctional in mood and related disorders. Anandamide, tetrahydrocannabinol (THC) and cannabidiol (CBD) variously combine antidepressant, antipsychotic, anxiolytic, analgesic, anticonvulsant actions, suggesting a therapeutic potential in mood and related disorders. Currently, cannabinoids find a role in pain control. Post mortem and other studies report EC system abnormalities in depression, schizophrenia and suicide. Abnormalities in the cannabinoid-1 receptor (CNR1) gene that codes for cannabinoid-1 (CB1) receptors are reported in psychiatric disorders. However, efficacy trials of cannabinoids in psychiatric disorders are limited but offer some encouragement. Research is needed to elucidate the role of the EC system in psychiatric disorders and for clinical trials with THC, CBD and synthetic cannabinoids to assess their therapeutic potential. © 2011 John Wiley & Sons A/S.

The influence of cognitive dysfunction on benefit from learning and memory rehabilitation in MS: A sub-analysis of the MEMREHAB trial.

PubMed

Chiaravalloti, Nancy D; DeLuca, John

2015-10-01

This study examined the influence of processing speed (PS) on benefit from treatment with the modified Story Memory Technique(©) (mSMT), a behavioral intervention shown to improve new learning and memory in multiple sclerosis (MS). This double-blind, placebo-controlled, randomized clinical trial included 85 participants with clinically definite MS, 45 assigned to the treatment group and 40 to the placebo-control group. Participants completed baseline and follow-up neuropsychological assessment. The present study represents a post-hoc analysis to examine the role of PS on treatment efficacy. The treatment group showed a significantly improved CVLT learning slope relative to the placebo group post-treatment, after co-varying PS performance. SDMT performance was a significant predictor of benefit from mSMT treatment, beyond group assignment. Post-hoc analysis indicated a significant correlation between the SDMT and overall cognition, indicating that the SDMT may be serving as a proxy for overall cognitive impairment. Performance on measures of cognitive dysfunction aside from learning and memory impact the benefit of mSMT treatment. While the current study focused on PS as a critical factor, PS may be serving as a marker for generalized cognitive dysfunction. Implications for cognitive rehabilitation in MS are discussed. © The Author(s), 2015.

Allogeneic mesenchymal precursor cells (MPCs): an innovative approach to treating advanced heart failure.

PubMed

Westerdahl, Daniel E; Chang, David H; Hamilton, Michele A; Nakamura, Mamoo; Henry, Timothy D

2016-09-01

Over 37 million people worldwide are living with Heart Failure (HF). Advancements in medical therapy have improved mortality primarily by slowing the progression of left ventricular dysfunction and debilitating symptoms. Ultimately, heart transplantation, durable mechanical circulatory support (MCS), or palliative care are the only options for patients with end-stage HF. Regenerative therapies offer an innovative approach, focused on reversing myocardial dysfunction and restoring healthy myocardial tissue. Initial clinical trials using autologous (self-donated) bone marrow mononuclear cells (BMMCs) demonstrated excellent safety, but only modest efficacy. Challenges with autologous stem cells include reduced quality and efficacy with increased patient age. The use of allogeneic mesenchymal precursor cells (MPCs) offers an "off the shelf" therapy, with consistent potency and less variability than autologous cells. Preclinical and initial clinical trials with allogeneic MPCs have been encouraging, providing the support for a large ongoing Phase III trial-DREAM-HF. We provide a comprehensive review of preclinical and clinical data supporting MPCs as a therapeutic option for HF patients. The current data suggest allogeneic MPCs are a promising therapy for HF patients. The results of DREAM-HF will determine whether allogeneic MPCs can decrease major adverse clinical events (MACE) in advanced HF patients.

Investigational opioid antagonists for treating opioid-induced bowel dysfunction.

PubMed

Mozaffari, Shilan; Nikfar, Shekoufeh; Abdollahi, Mohammad

2018-03-01

Opioids have been highlighted for their role in pain relief among cancer and non-cancer patients. Novel agents have been investigated to reduce opioid-induced constipation (OIC) as the main adverse effect that may lead to treatment discontinuation. Development of peripherally acting mu-opioid receptor antagonists (PAMORA) has resulted in a novel approach to preserve the efficacy of pain control along with less OIC. Areas covered: Clinical evidence for investigational PAMORAs was reviewed and clinical trials on investigational agents to reduce OIC were included. TD-1211 is currently being evaluated in Phase II clinical trial. Oxycodone-naltrexone and ADL-5945 went through Phase III clinical trials, but have been discontinued. Expert opinion: There is a substantial need to develop agents with specific pharmacokinetic properties to meet the needs of patients with underlying diseases. Holding the efficacy of a medicine with the highest selectivity on targeted receptors and the least adverse effects is the main approach in upcoming investigations to improve patients' quality of life (QoL). Novel agents to reduce opioid-induced bowel dysfunction (OIBD) that do not reverse peripherally mediated pain analgesia are of great interest. Direct comparison of available agents in this field is lacking in the literature.

No. 279-Female Sexual Health Consensus Clinical Guidelines.

PubMed

Lamont, John; Bajzak, Krisztina; Bouchard, Céline; Burnett, Margaret; Byers, Sandra; Cohen, Trevor; Fisher, William; Holzapfel, Stephen; Senikas, Vyta

2018-06-01

To establish national guidelines for the assessment of women's sexual health concerns and the provision of sexual health care for women. Published literature was retrieved through searches of PubMed, CINAHL, and the Cochrane Library from May to October 2010, using appropriate controlled vocabulary (e.g., sexuality, "sexual dysfunction," "physiological," dyspareunia) and key words (e.g., sexual dysfunction, sex therapy, anorgasmia). Results were restricted, where possible, to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Each article was screened for relevance and the full text acquired if determined to be relevant. The evidence obtained was reviewed and evaluated by the members of the Expert Workgroup established by The Society of Obstetricians and Gynaecologists of Canada. The quality of evidence was evaluated and recommendations made using the use of criteria described by the Canadian Task Force on Preventive Health Care (Table). Copyright © 2018. Published by Elsevier Inc.

The First Year of the Food and Drug Administration Oncology Center of Excellence: Landmark Approvals in a Dynamic Regulatory Environment.

PubMed

Goldberg, Kirsten B; Blumenthal, Gideon M; Pazdur, Richard

The Food and Drug Administration formally established the Oncology Center of Excellence (OCE) in January 2017, as authorized by the 21st Century Cures Act, to expedite the development and review of certain drugs, biologics, and devices for the treatment of cancer. In its first year, the OCE conducted the clinical reviews for several products, including the first 2 chimeric antigen receptor T-cell therapies approved for the treatment of advanced hematologic malignancies and an in vitro diagnostic next-generation sequencing panel, FoundationOne CDx. The OCE also worked with professional societies and patient advocates on efforts to modernize clinical trial eligibility criteria, resulting in recommendations regarding minimal age, brain metastases, organ dysfunction, and human immunodeficiency virus coinfection. Altogether in 2017, the Food and Drug Administration approved 16 new drug and biologic applications, 30 supplemental drug and biologic applications, and 2 biosimilar applications in oncology.

Effects of liraglutide on ovarian dysfunction in polycystic ovary syndrome: a randomized clinical trial.

PubMed

Nylander, Malin; Frøssing, Signe; Clausen, Helle V; Kistorp, Caroline; Faber, Jens; Skouby, Sven O

2017-07-01

Polycystic ovary syndrome (PCOS) encompasses an ovarian and a metabolic dysfunction. Glucagon-like peptide-1 (GLP-1) analogues facilitate weight loss and ameliorate metabolic dysfunction in overweight women with PCOS, but their effect on ovarian dysfunction is scarcely reported. In a double-blind, randomized trial, 72 women with PCOS were allocated to intervention with the GLP-1 analogue liraglutide or placebo (1.8 mg/day), in a 2:1 ratio. At baseline and 26-week follow-up, bleeding pattern, levels of AMH, sex hormones and gonadotrophins were assessed and ovarian morphology evaluated. Liraglutide caused 5.2 kg (95% CI 3.0 to 7.5, P < 0.0001) weight loss compared with placebo. Bleeding ratio improved with liraglutide: 0.28 (95% CI 0.20 to 0.36, P < 0.001); placebo: 0.14 (95% CI 0.02 to 0.26, P < 0.05); between-group difference: 0.14 (95% CI 0.03 to 0.24, P < 0.05). In the liraglutide group, SHBG increased by 7.4 nmol/L (95% CI 4.1 to 10.7) and free testosterone decreased by 0.005 nmol/L (95% CI -0.009 to -0.001). Ovarian volume decreased by -1.6 ml (95% CI -3.3 to 0.1) with liraglutide versus placebo. Nausea and constipation were more prevalent in the liraglutide group. Liraglutide improved markers of ovarian function in overweight women with PCOS, and might be a possible intervention. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Controlled randomized clinical trial of spirituality integrated psychotherapy, cognitive-behavioral therapy and medication intervention on depressive symptoms and dysfunctional attitudes in patients with dysthymic disorder.

PubMed

Ebrahimi, Amrollah; Neshatdoost, Hamid Taher; Mousavi, Seyed Ghafur; Asadollahi, Ghorban Ali; Nasiri, Hamid

2013-01-01

Due to the controversy over efficacy of cognitive-behavioral therapy for chronic depression, recently, there has been an increasingly tendency toward therapeutic methods based on the cultural and spiritual approaches. The aim of this research was to compare efficacy of spiritual integrated psychotherapy (SIPT) and cognitive-behavioral therapy (CBT) on the intensity of depression symptoms and dysfunctional attitudes of patients with dysthymic disorder. This study had a mixed qualitative and quantitative design. In the first phase, SIPT model was prepared and, in the second phase, a double-blind random clinical trial was performed. Sixty-two patients with dysthymic disorder were selected from several centers include Nour and Alzahra Medical Center, Counseling Centers of Isfahan University of Medical Sciences and Goldis in Isfahan. The participants were randomly assigned to three experimental groups and one control group. The first group received 8 sessions treatment of SIPT, second groups also had 8 sessions of cognitive-behavioral therapy, which was specific to dysthymic disorder and third group were under antidepressant treatment. Beck depression inventory and dysfunctional attitudes scale were used to evaluate all the participants in four measurement stages. The data were analyzed using MANCOVA repeated measure method. The results revealed that SIPT had more efficacy than medication based on both scales (P < 0.01); however, it was not different from CBT. SIPT was more effective on the modification of dysfunctional attitudes compared with CBT and medication (P < 0.05). These findings supported the efficacy of psychotherapy enriched with cultural capacities and religious teachings.

Borderline Personality Disorder and Oxytocin: Review of Clinical Trials and Future Directions.

PubMed

Amad, Ali; Thomas, Pierre; Perez-Rodriguez, M Mercedes

2015-01-01

Borderline personality disorder (BPD) is a common mental disorder characterized by a pervasive pattern of emotional Borderline personality disorder (BPD) is a common mental disorder characterized by a pervasive pattern of emotional lability, impulsivity, interpersonal difficulties, identity disturbances, and disturbed cognition. Traditional pharmacotherapies are effective in treating some of these core symptoms but have only modest effects on the domain of interpersonal dysfunction of BPD. Thus there is a need to develop new, neurobiologically informed pharmacological treatments for BPD. This review focuses on the potential use of intranasal oxytocin (OXT), which has key roles in the regulation of complex social cognition and behaviors, to target symptoms of interpersonal dysfunction in BPD. Surprisingly, despite promising data on the prosocial effects of OXT, only 5 trials in BPD have been published to date. These trials show mixed results with on one hand, a decrease of emotional responses to stress and on the other hand, some "paradoxical" reactions with worsened interpersonal anxiety and decreased cooperative behavior. These mixed results are interpreted according to different theoretical models and also in light of some methodological limitations. Further studies are needed to understand the effect of OXT in patients with BPD and ongoing clinical trials will provide some answers to remaining questions on the use of OXT in BPD. Recommendations for future studies are also proposed in this review.

Lifestyle modifications and erectile dysfunction: what can be expected?

PubMed Central

Maiorino, Maria Ida; Bellastella, Giuseppe; Esposito, Katherine

2015-01-01

Erectile dysfunction (ED) is a common medical disorder whose prevalence is increasing worldwide. Modifiable risk factors for ED include smoking, lack of physical activity, wrong diets, overweight or obesity, metabolic syndrome, and excessive alcohol consumption. Quite interestingly, all these metabolic conditions are strongly associated with a pro-inflammatory state that results in endothelial dysfunction by decreasing the availability of nitric oxide (NO), which is the driving force of the blood genital flow. Lifestyle and nutrition have been recognized as central factors influencing both vascular NO production, testosterone levels, and erectile function. Moreover, it has also been suggested that lifestyle habits that decrease low-grade clinical inflammation may have a role in the improvement of erectile function. In clinical trials, lifestyle modifications were effective in ameliorating ED or restoring absent ED in people with obesity or metabolic syndrome. Therefore, promotion of healthful lifestyles would yield great benefits in reducing the burden of sexual dysfunction. Efforts, in order to implement educative strategies for healthy lifestyle, should be addressed. PMID:25248655

The Relationship between Dysfunctional Family Environments and Family Member Food Intake.

ERIC Educational Resources Information Center

Kintner, Martha; And Others

1981-01-01

Explores relationships between family environment and family food intake. Findings indicate a significant negative relationship between the family's dysfunctional environment (indicated by high conflict, control, and organization) and family dietary intake. A significant positive relationship was found between the family's cohesive and independent…

38 CFR 4.115a - Ratings of the genitourinary system-dysfunctions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Ratings of the genitourinary system—dysfunctions. Diseases of the genitourinary system generally result in... cover all symptoms resulting from genitourinary diseases, specific diagnoses may include a description... organ systems, estpecially cardiovascular 100 Persistent edema and albuminuria with BUN 40 to 80mg%; or...

Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome.

PubMed

Carcillo, Joseph A; Halstead, E Scott; Hall, Mark W; Nguyen, Trung C; Reeder, Ron; Aneja, Rajesh; Shakoory, Bita; Simon, Dennis

2017-06-01

We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis. Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes. Tertiary children's hospital PICU. One hundred consecutive severe sepsis admissions. Clinical data were recorded daily, and blood was collected twice weekly. Multiple organ failure developed in 75 cases and eight died. Multiple organ failure cases with any of the three inflammation phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and ferritin, p < 0.001) than multiple organ failure cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of macrophage activation syndrome and death were more common among multiple organ failure cases with any of the phenotypes (macrophage activation syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and death: 0/38, 0%; p = 0.002). Our approach to phenotype categorization remains hypothetical, and the phenotypes identified need to be confirmed in multicenter studies of pediatric multiple organ dysfunction syndrome.

Adrenergic support in septic shock: a critical review.

PubMed

Póvoa, Pedro; Carneiro, António H

2010-02-01

The definition of septic shock includes sepsis-induced hypotension despite adequate fluid resuscitation, along with the presence of organ perfusion abnormalities, and ultimately cell dysfunction. To restore adequate organ perfusion and cell homeostasis, cardiac output should be restored with volume infusion plus vasopressor agents as indicated. Appropriate arterial pressure for each individual patient and proper arterial oxygen content are key elements to restoring perfusion. Tissue perfusion can be monitored by markers of organ and mitochondrial function, namely urine output, level of consciousness, peripheral skin perfusion, central or mixed venous oxygen saturation, and lactate. The hemodynamic effects of the different vasopressor agents depend on the relative affinity to adrenergic receptors. Those with predominant alpha-agonist activity produce more vasoconstriction (inoconstrictors) while those with predominant beta-agonist stimulation increase cardiac performance (inodilators). The debate about whether one vasopressor agent is superior to another is still ongoing. The Surviving Sepsis Campaign guidelines refer to either norepinephrine or dopamine as the first-choice vasopressor agent to correct hypotension in septic shock. However, recent data from observational and controlled trials have challenged these recommendations concerning different adrenergic agents. As a result, our view on the prescription of vasopressors has changed from a probably oversimplified "one-size-fits-all" approach to a multimodal approach in vasopressor selection.

Concise Review: Mesenchymal Stem (Stromal) Cells: Biology and Preclinical Evidence for Therapeutic Potential for Organ Dysfunction Following Trauma or Sepsis.

PubMed

Matthay, Michael A; Pati, Shibani; Lee, Jae-Woo

2017-02-01

Several experimental studies have provided evidence that bone-marrow derived mesenchymal stem (stromal) cells (MSC) may be effective in treating critically ill surgical patients who develop traumatic brain injury, acute renal failure, or the acute respiratory distress syndrome. There is also preclinical evidence that MSC may be effective in treating sepsis-induced organ failure, including evidence that MSC have antimicrobial properties. This review considers preclinical studies with direct relevance to organ failure following trauma, sepsis or major infections that apply to critically ill patients. Progress has been made in understanding the mechanisms of benefit, including MSC release of paracrine factors, transfer of mitochondria, and elaboration of exosomes and microvesicles. Regardless of how well they are designed, preclinical studies have limitations in modeling the complexity of clinical syndromes, especially in patients who are critically ill. In order to facilitate translation of the preclinical studies of MSC to critically ill patients, there will need to be more standardization regarding MSC production with a focus on culture methods and cell characterization. Finally, well designed clinical trials will be needed in critically ill patient to assess safety and efficacy. Stem Cells 2017;35:316-324. © 2016 AlphaMed Press.

[Application of yellow turpentine baths in patients with chronic prostatitis complicated by sexual dysfunctions].

PubMed

2005-01-01

Patients with chronic prostatitis complicated by sexual dysfunction took turpentine baths with yellow solution in concentration rising from 5 to 55 ml solution per 200 l water, temperature 35-40 degrees C, duration 5-16 min, daily, 12-15 procedures. Yellow turpentine baths raise efficacy of treatment of patients with copulative dysfunction to 64% due to intensive arterial blood inflow to the sexual organs including the cavernous bodies of the penis.

PACAP/Receptor System in Urinary Bladder Dysfunction and Pelvic Pain Following Urinary Bladder Inflammation or Stress

PubMed Central

Girard, Beatrice M.; Tooke, Katharine; Vizzard, Margaret A.

2017-01-01

Complex organization of CNS and PNS pathways is necessary for the coordinated and reciprocal functions of the urinary bladder, urethra and urethral sphincters. Injury, inflammation, psychogenic stress or diseases that affect these nerve pathways and target organs can produce lower urinary tract (LUT) dysfunction. Numerous neuropeptide/receptor systems are expressed in the neural pathways of the LUT and non-neural components of the LUT (e.g., urothelium) also express peptides. One such neuropeptide receptor system, pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1) and its cognate receptor, PAC1 (Adcyap1r1), have tissue-specific distributions in the LUT. Mice with a genetic deletion of PACAP exhibit bladder dysfunction and altered somatic sensation. PACAP and associated receptors are expressed in the LUT and exhibit neuroplastic changes with neural injury, inflammation, and diseases of the LUT as well as psychogenic stress. Blockade of the PACAP/PAC1 receptor system reduces voiding frequency in preclinical animal models and transgenic mouse models that mirror some clinical symptoms of bladder dysfunction. A change in the balance of the expression and resulting function of the PACAP/receptor system in CNS and PNS bladder reflex pathways may underlie LUT dysfunction including symptoms of urinary urgency, increased voiding frequency, and visceral pain. The PACAP/receptor system in micturition pathways may represent a potential target for therapeutic intervention to reduce LUT dysfunction. PMID:29255407

International differences in clinical characteristics, management, and outcomes in acute heart failure patients: better short-term outcomes in patients enrolled in Eastern Europe and Russia in the PROTECT trial

PubMed Central

Mentz, Robert J.; Cotter, Gad; Cleland, John G.F.; Stevens, Susanna R.; Chiswell, Karen; Davison, Beth A.; Teerlink, John R.; Metra, Marco; Voors, Adriaan A.; Grinfeld, Liliana; Ruda, Mikhail; Mareev, Viacheslav; Lotan, Chaim; Bloomfield, Daniel M.; Fiuzat, Mona; Givertz, Michael M.; Ponikowski, Piotr; Massie, Barry M.; O’Connor, Christopher M.

2017-01-01

Aims The implications of geographical variation are unknown following adjustment for hospital length of stay (LOS) in heart failure (HF) trials that included patients whether or not they had systolic dysfunction. We investigated regional differences in an international acute HF trial. Methods and results The PROTECT trial investigated 2033 patients with acute HF and renal dysfunction hospitalized at 173 sites in 17 countries with randomization to rolofylline or placebo. We grouped enrolling countries into six regions. Baseline characteristics, in-hospital management, and outcomes were explored by region. The primary study outcome was 60-day mortality or cardiovascular/renal hospitalization. Secondary outcomes included 180-day mortality. Of 2033 patients, 33% were from Eastern Europe, 19% from Western Europe, 16% from Israel, 15% from North America, 14% from Russia, and 3% from Argentina. Marked differences in baseline characteristics, HF phenotype, in-hospital diuretic and vasodilator strategies, and LOS were observed by region. LOS was shortest in North America and Israel (median 5 days) and longest in Russia (median 15 days). Regional event rates varied significantly. Following multivariable adjustment, region was an independent predictor of the risk of mortality/hospitalization at 60 days, with the lowest risk in Russia (hazard ratio 0.39, 95% confidence interval 0.23–0.64 vs. Western Europe) due to lower rehospitalization; mortality differences were attenuated by 180 days. Conclusions In an international HF trial, there were differences in baseline characteristics, treatments, LOS, and rehospitalization amongst regions, but little difference in longer term mortality. Rehospitalization differences exist independent of LOS. This analysis may help inform future trial design and should be externally validated. PMID:24771609

Effect of the peels of two Citrus fruits on endothelium function in adolescents with excess weight: A triple-masked randomized trial

PubMed Central

Hashemi, Mohammad; Khosravi, Elham; Ghannadi, Alireza; Hashemipour, Mahin; Kelishadi, Roya

2015-01-01

Background: Obesity induces endothelial dysfunction even in the pediatric age group. The possible protective effects of fruits and herbal products on the endothelial dysfunction of obese children remain to be determined. This study aims to investigate the effects of lemon and sour orange peels on endothelial function of adolescents with excess weight. Materials and Methods: This triple-masked, randomized placebo-controlled trial was conducted for 1-month among 90 overweight and obese participants, aged 6-18 years. They were randomly assigned into three groups of equal number receiving daily oral capsules containing lemon or sour orange powder or placebo. Flow-mediated dilatation (FMD) was compared between three groups by using analysis of covariance. Results: Overall, 30 participants in the lemon group, 27 in the sour orange group and 29 in the control group completed the trial. After the trial, mean FMD was significantly (P < 0.001) higher in the lemon group (11.99 ± 4.05) and in the sour orange group (12.79 ± 5.47) than in the placebo group (6.45 ± 2.79). FMD percent change was 145.02 ± 24.34 in the lemon group, 142.04 ± 16.11 in the sour orange group, and 46.73 ± 5.16 in controls (P < 0.001). Conclusion: This trial showed that consumption of extracts of lemon and sour orange peels, which contain plenty amounts of antioxidants, flavonoids, pectin, and vitamin C, might have significant benefits on endothelial function in children and adolescents with excess weight. Trial registry code: IRCT201311201434N10. PMID:26664417

The outcomes and prognostic factors of acute respiratory failure in the patients 90 years old and over.

PubMed

Chen, Wan-Ling; Chen, Chin-Ming; Kung, Shu-Chen; Wang, Ching-Min; Lai, Chih-Cheng; Chao, Chien-Ming

2018-01-23

This retrospective cohort study investigated the outcomes and prognostic factors in nonagenarians (patients 90 years old or older) with acute respiratory failure. Between 2006 and 2016, all nonagenarians with acute respiratory failure requiring invasive mechanical ventilation (MV) were enrolled. Outcomes including in-hospital mortality and ventilator dependency were measured. A total of 173 nonagenarians with acute respiratory failure were admitted to the intensive care unit (ICU). A total of 56 patients died during the hospital stay and the rate of in-hospital mortality was 32.4%. Patients with higher APACHE (Acute Physiology and Chronic Health Evaluation) II scores (adjusted odds ratio [OR], 5.91; 95 % CI, 1.55-22.45; p = 0.009, APACHE II scores ≥ 25 vs APACHE II scores < 15), use of vasoactive agent (adjust OR, 2.67; 95% CI, 1.12-6.37; p = 0.03) and more organ dysfunction (adjusted OR, 11.13; 95% CI, 3.38-36.36, p < 0.001; ≥ 3 organ dysfunction vs ≤ 1 organ dysfunction) were more likely to die. Among the 117 survivors, 25 (21.4%) patients became dependent on MV. Female gender (adjusted OR, 3.53; 95% CI, 1.16-10.76, p = 0.027) and poor consciousness level (adjusted OR, 4.98; 95% CI, 1.41-17.58, p = 0.013) were associated with MV dependency. In conclusion, the mortality rate of nonagenarians with acute respiratory failure was high, especially for those with higher APACHE II scores or more organ dysfunction.

Endocrine dysfunction in sepsis: a beneficial or deleterious host response?

PubMed Central

Gheorghiţă, Valeriu; Barbu, Alina Elena; Gheorghiu, Monica Livia; Căruntu, Florin Alexandru

2015-01-01

Sepsis is a systemic, deleterious inflammatory host response triggered by an infective agent leading to severe sepsis, septic shock and multi-organ failure. The host response to infection involves a complex, organized and coherent interaction between immune, autonomic, neuroendocrine and behavioral systems. Recent data have confirmed that disturbances of the autonomic nervous and neuroendocrine systems could contribute to sepsis-induced organ dysfunction. Through this review, we aimed to summarize the current knowledge about the endocrine dysfunction as response to sepsis, specifically addressed to vasopressin, copeptin, cortisol, insulin and leptin. We searched the following readily accessible, clinically relevant databases: PubMed, UpToDate, BioMed Central. The immune system could be regarded as a “diffuse sensory organ” that signals the presence of pathogens to the brain through different pathways, such as the vagus nerve, endothelial activation/dysfunction, cytokines and neurotoxic mediators and the circumventricular organs, especially the neurohypophysis. The hormonal profile changes substantially as a consequence of inflammatory mediators and microorganism products leading to inappropriately low levels of vasopressin, sick euthyroid syndrome, reduced adrenal responsiveness to ACTH, insulin resistance, hyperglycemia as well as hyperleptinemia. In conclusion, clinical diagnosis of this “pan-endocrine illness” is frequently challenging due to the many limiting factors. The most important benefits of endocrine markers in the management of sepsis may be reflected by their potential to be used as biomarkers in different scoring systems to estimate the severity of the disease and the risk of death. PMID:25763364

Influence of Obesity Diagnosis With Organ Dysfunction, Mortality, and Resource Use Among Children Hospitalized With Infection in the United States.

PubMed

Maley, Nidhi; Gebremariam, Achamyeleh; Odetola, Folafoluwa; Singer, Kanakadurga

2017-06-01

Sepsis induces inflammation in response to infection and is a major cause of mortality and hospitalization in children. Obesity induces chronic inflammation leading to many clinical manifestations. Our understanding of the impact of obesity on diseases, such as infection and sepsis, is limited. The objective of this study was to evaluate the association of obesity with organ dysfunction, mortality, duration, and charges during among US children hospitalized with infection. Retrospective study of hospitalizations in children with infection aged 0 to 20 years, using the 2009 Kids' Inpatient Database. Of 3.4 million hospitalizations, 357 701 were for infection, 5685 of which were reported as obese children. Obese patients had higher rates of organ dysfunction (7.35% vs 5.5%, P < .01), longer hospital stays (4.1 vs 3.5 days, P < .001), and accrued higher charges (US$29 019 vs US$21 200, P < .001). In multivariable analysis, mortality did not differ by obesity status (odds ratio: 0.56, 95% confidence interval: 0.23-1.34), however severity of illness modified the association between obesity status and the other outcomes. While there was no difference in in-hospital mortality by obesity diagnosis, variation in organ dysfunction, hospital stay, and hospital charges according to obesity status was mediated by illness severity. Findings from this study have significant implications for targeted approaches to mitigate the burden of obesity on infection and sepsis.

Improved recovery of regional left ventricular function after PCI of chronic total occlusion in STEMI patients: a cardiovascular magnetic resonance study of the randomized controlled EXPLORE trial.

PubMed

Elias, Joëlle; van Dongen, Ivo M; Hoebers, Loes P; Ouweneel, Dagmar M; Claessen, Bimmer E P M; Råmunddal, Truls; Laanmets, Peep; Eriksen, Erlend; van der Schaaf, René J; Ioanes, Dan; Nijveldt, Robin; Tijssen, Jan G; Hirsch, Alexander; Henriques, José P S

2017-07-19

The Evaluating Xience and left ventricular function in PCI on occlusiOns afteR STEMI (EXPLORE) trial did not show a significant benefit of percutaneous coronary intervention (PCI) of the concurrent chronic total occlusion (CTO) in ST-segment elevation myocardial infarction (STEMI) patients on global left ventricular (LV) systolic function. However a possible treatment effect will be most pronounced in the CTO territory. Therefore, we aimed to study the effect of CTO PCI compared to no-CTO PCI on the recovery of regional LV function, particularly in the CTO territory. Using cardiovascular magnetic resonance (CMR) we studied 180 of the 302 EXPLORE patients with serial CMR (baseline and 4 months follow-up). Segmental wall thickening (SWT) was quantified on cine images by an independent core laboratory. Dysfunctional segments were defined as SWT < 45%. Dysfunctional segments were further analyzed by viability (transmural extent of infarction (TEI) ≤50%.). All outcomes were stratified for randomization treatment. In the dysfunctional segments in the CTO territory recovery of SWT was better after CTO PCI compared to no-CTO PCI (ΔSWT 17 ± 27% vs 11 ± 23%, p = 0.03). This recovery was most pronounced in the dysfunctional but viable segments(TEI < 50%) (ΔSWT 17 ± 27% vs 11 ± 22%, p = 0.02). Furthermore in the CTO territory, recovery of SWT was significantly better in the dysfunctional segments in patients with Rentrop grade 2-3 collaterals compared to grade 0-1 collaterals to the CTO (16 ± 26% versus 11 ± 24%, p = 0.04). CTO PCI compared with no-CTO PCI is associated with a greater recovery of regional systolic function in the CTO territory, especially in the dysfunctional but viable segments. Further research is needed to evaluate the use of CMR in selecting post-STEMI patients for CTO PCI and the effect of regional LV function recovery on clinical outcome. Trialregister.nl NTR1108 , Date registered NTR: 30-okt-2007.

Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial

PubMed Central

Francois, Bruno; Daix, Thomas; Walton, Andrew H.; Shotwell, Matthew S.; Unsinger, Jacqueline; Rimmelé, Thomas; Blood, Teresa; Morre, Michel; Gregoire, Anne; Mayo, Gail A.; Blood, Jane; Durum, Scott K.; Hotchkiss, Richard S.

2018-01-01

BACKGROUND. A defining pathophysiologic feature of sepsis is profound apoptosis-induced death and depletion of CD4+ and CD8+ T cells. Interleukin-7 (IL-7) is an antiapoptotic common γ-chain cytokine that is essential for lymphocyte proliferation and survival. Clinical trials of IL-7 in over 390 oncologic and lymphopenic patients showed that IL-7 was safe, invariably increased CD4+ and CD8+ lymphocyte counts, and improved immunity. METHODS. We conducted a prospective, randomized, double-blind, placebo-controlled trial of recombinant human IL-7 (CYT107) in patients with septic shock and severe lymphopenia. Twenty-seven patients at academic sites in France and the United States received CYT107 or placebo for 4 weeks. Primary aims were to determine the safety of CYT107 in sepsis and its ability to reverse lymphopenia. RESULTS. CYT107 was well tolerated without evidence of inducing cytokine storm or worsening inflammation or organ dysfunction. CYT107 caused a 3- to 4-fold increase in absolute lymphocyte counts and in circulating CD4+ and CD8+ T cells that persisted for weeks after drug administration. CYT107 also increased T cell proliferation and activation. CONCLUSIONS. This is the first trial of an immunoadjuvant therapy targeting defects in adaptive immunity in patients with sepsis. CYT107 reversed the marked loss of CD4+ and CD8+ immune effector cells, a hallmark of sepsis and a likely key mechanism in its morbidity and mortality. CYT107 represents a potential new way forward in the treatment of patients with sepsis by restoring adaptive immunity. Such immune-based therapy should be broadly protective against diverse pathogens including multidrug resistant bacteria that preferentially target patients with impaired immunity. TRIAL REGISTRATION. Trials registered at clinicaltrials.gov: NCT02640807 and NCT02797431. FUNDING. Revimmune, NIH National Institute of General Medical Sciences GM44118. PMID:29515037

Cerebral Dysfunctions Related to Perinatal Organic Damage: Clinical-Neuropathologic Correlations.

ERIC Educational Resources Information Center

Towbin, Abraham

1978-01-01

Recent neuropathology studies identify hypoxia as the main cause of perinatal cerebral damage. Cerebral lesions present at birth, with transition to chronic scar lesions, are correlated to mental retardation, cerebral palsy, epilepsy, and minimal brain dysfunction. Gestation age and severity of hypoxic exposure essentially determine the cerebral…

Smooth muscle membrane organization in the normal and dysfunctional human urinary bladder: a structural analysis.

PubMed

Burkhard, Fiona C; Monastyrskaya, Katia; Studer, Urs E; Draeger, Annette

2005-01-01

The decline in contractile properties is a characteristic feature of the dysfunctional bladder as a result of infravesical outlet obstruction. During clinical progression of the disease, smooth muscle cells undergo structural modifications. Since adaptations to constant changes in length require a high degree of structural organization within the sarcolemma, we have investigated the expression of several proteins, which are involved in smooth muscle membrane organization, in specimens derived from normal and dysfunctional organs. Specimen from patients with urodynamically normal/equivocal (n = 4), obstructed (n = 2), and acontractile (n = 2) bladders were analyzed relative to their structural features and sarcolemmal protein profile. Smooth muscle cells within the normal urinary bladder display a distinct sarcolemmal domain structure, characterized by firm actin-attachment sites, alternating with flexible "hinge" regions. In obstructed bladders, foci of cells displaying degenerative sarcolemmal changes alternate with areas of hypertrophic cells in which the membrane appears unaffected. In acontractile organs, the overall membrane structure remains intact, however annexin 6, a protein belonging to a family of Ca2+-dependent, "membrane-organizers," is downregulated. Degenerative changes in smooth muscle cells, which are chronically working against high resistance, are preferentially located within the actin-attachment sites. In acontractile bladders, the downregulation of annexin 6 might have a bearing on the fine-tuning of the plasma membrane during contraction/relaxation cycles. Copyright 2005 Wiley-Liss, Inc.

Copeptin in patients with heart failure and preserved ejection fraction: a report from the prospective KaRen-study

PubMed Central

Hage, Camilla; Lund, Lars H; Donal, Erwan; Daubert, Jean-Claude; Linde, Cecilia; Mellbin, Linda

2015-01-01

Introduction Underlying mechanisms of heart failure (HF) with preserved ejection fraction (HFPEF) remain unknown. We explored copeptin, a biomarker of the arginine vasopressin system, hypothesising that copeptin in HFPEF is elevated, associated with diastolic dysfunction and N-terminal pro-brain natriuretic peptide (NT-proBNP) and predictive of HF hospitalisation and mortality. Methods and analysis In a prospective observational substudy of the The Karolinska Rennes (KaRen) 86 patients with symptoms of acute HF and ejection fraction (EF) ≥45% were enrolled. After 4–8 weeks, blood sampling and echocardiography was performed. Plasma-copeptin was analysed in 86 patients and 62 healthy controls. Patients were followed in median 579 days (quartile 1; quartile 3 (Q1;Q3) 276;1178) regarding the composite end point all-cause mortality or HF hospitalisation. Ethics and dissemination The patients with HFPEF had higher copeptin levels, median 13.56 pmol/L (Q1;Q3 8.56;20.55) than controls 5.98 pmol/L (4.15;9.42; p<0.001). Diastolic dysfunction, assessable in 75/86 patients, was present in 45 and absent in 30 patients. Copeptin did not differ regarding diastolic dysfunction and did not correlate with cardiac function but with NT-proBNP (r=0.223; p value=0.040). In univariate Cox regression analysis log copeptin predicted the composite end point (HR 1.56 (95% CI 1.03 to 2.38; p value=0.037)) but not after adjusting for NT-proBNP (HR 1.39 (95% CI 0.91 to 2.12; p value=0.125)). Conclusions In the present patients with HFPEF, copeptin is elevated, correlates with NT-proBNP but not markers of diastolic dysfunction, and has prognostic implications, however blunted after adjustment for NT-proBNP. The HFPEF pathophysiology may be better reflected by markers of neurohormonal activation than by diastolic dysfunction. Trial registration number ClinicalTrials.gov NCT00774709. PMID:26568833

Galectin-3 in heart failure with preserved ejection fraction. A RELAX trial substudy (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure).

PubMed

AbouEzzeddine, Omar F; Haines, Phillip; Stevens, Susanna; Nativi-Nicolau, Jose; Felker, G Michael; Borlaug, Barry A; Chen, Horng H; Tracy, Russell P; Braunwald, Eugene; Redfield, Margaret M

2015-03-01

This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains. Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased with normal aging and renal dysfunction. Cardiac fibrosis may contribute to cardiac dysfunction, exercise intolerance, and congestion in HFpEF. Two hundred eight patients from the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. Pathophysiological domains assessed included biomarkers of neurohumoral activation, fibrosis, inflammation and myocardial necrosis, congestion severity and quality of life, cardiac structure and function, and exercise performance. Analysis adjusted for age, sex, and/or cystatin-C levels. Potential interaction between baseline Gal-3 and treatment (sildenafil) effect on the RELAX study primary endpoint (change in peak oxygen consumption) was tested. Gal-3 levels were associated with age and severity of renal dysfunction. Adjusting for age, sex, and/or cystatin-C, Gal-3 was not associated with biomarkers of neurohumoral activation, fibrosis, inflammation or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53). In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function when interpreting Gal-3 levels, and call into question the value of Gal-3 to quantify disease severity in overt HFpEF. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial.

PubMed

Nurnberg, H George; Hensley, Paula L; Gelenberg, Alan J; Fava, Maurizio; Lauriello, John; Paine, Susan

2003-01-01

Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score < or =10) in both groups for the study duration. In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.

Can Valeriana officinalis root extract prevent early postoperative cognitive dysfunction after CABG surgery? A randomized, double-blind, placebo-controlled trial.

PubMed

Hassani, Soghra; Alipour, Abbas; Darvishi Khezri, Hadi; Firouzian, Abolfazl; Emami Zeydi, Amir; Gholipour Baradari, Afshin; Ghafari, Rahman; Habibi, Wali-Allah; Tahmasebi, Homeyra; Alipour, Fatemeh; Ebrahim Zadeh, Pooneh

2015-03-01

We hypothesized that valerian root might prevent cognitive dysfunction in coronary artery bypass graft (CABG) surgery patients through stimulating serotonin receptors and anti-inflammatory activity. The aim of this study was to evaluate the effect of Valeriana officinalis root extract on prevention of early postoperative cognitive dysfunction after on-pump CABG surgery. In a randomized, double-blind, placebo-controlled trial, 61 patients, aged between 30 and 70 years, scheduled for elective CABG surgery using cardiopulmonary bypass (CPB), were recruited into the study. Patients were randomly divided into two groups who received either one valerian capsule containing 530 mg of valerian root extract (1,060 mg/daily) or placebo capsule each 12 h for 8 weeks, respectively. For all patients, cognitive brain function was evaluated before the surgery and at 10-day and 2-month follow-up by Mini Mental State Examination (MMSE) test. Mean MMSE score decreased from 27.03 ± 2.02 in the preoperative period to 26.52 ± 1.82 at the 10th day and then increased to 27.45 ± 1.36 at the 60th day in the valerian group. Conversely, its variation was reduced significantly after 60 days in the placebo group, 27.37 ± 1.87 at the baseline to 24 ± 1.91 at the 10th day, and consequently slightly increased to 24.83 ± 1.66 at the 60th day. Valerian prophylaxis reduced odds of cognitive dysfunction compared to placebo group (OR = 0.108, 95 % CI 0.022-0.545). We concluded that, based on this study, the cognitive state of patients in the valerian group was better than that in the placebo group after CABG; therefore, it seems that the use of V. officinalis root extract may prevent early postoperative cognitive dysfunction after on-pump CABG surgery.

Cognitive enhancement treatments for bipolar disorder: A systematic review and methodological recommendations.

PubMed

Miskowiak, Kamilla W; Carvalho, André F; Vieta, Eduard; Kessing, Lars V

2016-10-01

Cognitive dysfunction is an emerging treatment target in bipolar disorder (BD). Several trials have assessed the efficacy of novel pharmacological and psychological treatments on cognition in BD but the findings are contradictory and unclear. A systematic search following the PRISMA guidelines was conducted on PubMed and PsychInfo. Eligible articles reported randomized, controlled or open-label trials investigating pharmacological or psychological treatments targeting cognitive dysfunction in BD. The quality of the identified randomized controlled trials (RCTs) was evaluated with the Cochrane Collaboration's Risk of Bias tool. We identified 19 eligible studies of which 13 were RCTs and six were open-label or non-randomized studies. The findings regarding efficacy on cognition were overall disappointing or preliminary, possibly due to several methodological challenges. For the RCTs, the risk of bias was high in nine cases, unclear in one case and low in three cases. Key reasons for the high risk of bias were lack of details on the randomization process, suboptimal handling of missing data and lack of a priori priority between cognition outcomes. Other challenges were the lack of consensus on whether and how to screen for cognitive impairment and on how to assess efficacy on cognition. In conclusion, methodological problems are likely to impede the success rates of cognition trials in BD. We recommend adherence to the CONSORT guidelines for RCTs, screening for cognitive impairment before inclusion of trial participants and selection of one primary cognition outcome. Future implementation of a 'neurocircuitry-based' biomarker model to evaluate neural target engagement is warranted. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone improves postprandial endothelial dysfunction in patients with borderline and stage 1 hypertension.

PubMed

Kajikawa, Masato; Maruhashi, Tatsuya; Hidaka, Takayuki; Nakano, Yukiko; Kurisu, Satoshi; Matsumoto, Takeshi; Iwamoto, Yumiko; Kishimoto, Shinji; Matsui, Shogo; Aibara, Yoshiki; Yusoff, Farina Mohamad; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Noma, Kensuke; Nakashima, Ayumu; Watanabe, Takuya; Tone, Hiroshi; Hibi, Masanobu; Osaki, Noriko; Katsuragi, Yoshihisa; Higashi, Yukihito

2018-01-12

The purpose of this study was to evaluate acute effects of coffee with a high content of chlorogenic acids and different hydroxyhydroquinone contents on postprandial endothelial dysfunction. This was a single-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 37 patients with borderline or stage 1 hypertension were randomized to two study groups. The participants consumed a test meal with a single intake of the test coffee. Subjects in the Study 1 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or placebo coffee with crossover. Endothelial function assessed by flow-mediated vasodilation and plasma concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after coffee intake. Compared with baseline values, single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone, but not coffee with a high content of chlorogenic acids and high content of hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow-mediated vasodilation and decreased circulating 8-isoprostane levels. These findings suggest that a single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone is effective for improving postprandial endothelial dysfunction. URL for Clinical Trial: https://upload.umin.ac.jp ; Registration Number for Clinical Trial: UMIN000013283.

Motor Learning Versus StandardWalking Exercise in Older Adults with Subclinical Gait Dysfunction: A Randomized Clinical Trial

PubMed Central

Brach, Jennifer S.; Van Swearingen, Jessie M.; Perera, Subashan; Wert, David M.; Studenski, Stephanie

2013-01-01

Background Current exercise recommendationsfocus on endurance and strength, but rarely incorporate principles of motor learning. Motor learning exerciseis designed to address neurological aspects of movement. Motor learning exercise has not been evaluated in older adults with subclinical gait dysfunction. Objectives Tocompare motor learning versus standard exercise on measures of mobility and perceived function and disability. Design Single-blind randomized trial. Setting University research center. Participants Olderadults (n=40), mean age 77.1±6.0 years), who had normal walking speed (≥1.0 m/s) and impaired motor skill (Figure of 8 walk time > 8 s). Interventions The motor learning program (ML) incorporated goal-oriented stepping and walking to promote timing and coordination within the phases of the gait cycle. The standard program (S) employed endurance training by treadmill walking.Both included strength training and were offered twice weekly for one hour for 12 weeks. Measurements Primary outcomes included mobility performance (gait efficiency, motor skill in walking, gait speed, and walking endurance)and secondary outcomes included perceived function and disability (Late Life Function and Disability Instrument). Results 38 of 40 participants completed the trial (ML, n=18; S, n=20). ML improved more than Sin gait speed (0.13 vs. 0.05 m/s, p=0.008) and motor skill (−2.2 vs. −0.89 s, p<0.0001). Both groups improved in walking endurance (28.3 and 22.9m, but did not differ significantly p=0.14). Changes in gait efficiency and perceived function and disability were not different between the groups (p>0.10). Conclusion In older adults with subclinical gait dysfunction, motor learning exercise improved some parameters of mobility performance more than standard exercise. PMID:24219189

Global Epidemiology of Pediatric Severe Sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study

PubMed Central

Weiss, Scott L.; Pappachan, John; Wheeler, Derek; Jaramillo-Bustamante, Juan C.; Salloo, Asma; Singhi, Sunit C.; Erickson, Simon; Roy, Jason A.; Bush, Jenny L.; Nadkarni, Vinay M.; Thomas, Neal J.

2015-01-01

Rationale: Limited data exist about the international burden of severe sepsis in critically ill children. Objectives: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. Methods: A point prevalence study was conducted on 5 days throughout 2013–2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. Measurements and Main Results: Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6–8.9%). The patients’ median age was 3.0 (interquartile range [IQR], 0.7–11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0–25), and vasoactive-free days were 23 (IQR, 12–28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5–10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,437 patients per group. Conclusions: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted. PMID:25734408

A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy.

PubMed

Lawrence, J A; Griffin, L; Balcueva, E P; Groteluschen, D L; Samuel, T A; Lesser, G J; Naughton, M J; Case, L D; Shaw, E G; Rapp, S R

2016-02-01

Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. Women who received adjuvant chemotherapy 1-5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory-the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p = 0.033) and HVLT-R Discrimination (p = 0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results.

Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study.

PubMed

Weiss, Scott L; Fitzgerald, Julie C; Pappachan, John; Wheeler, Derek; Jaramillo-Bustamante, Juan C; Salloo, Asma; Singhi, Sunit C; Erickson, Simon; Roy, Jason A; Bush, Jenny L; Nadkarni, Vinay M; Thomas, Neal J

2015-05-15

Limited data exist about the international burden of severe sepsis in critically ill children. To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. A point prevalence study was conducted on 5 days throughout 2013-2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6-8.9%). The patients' median age was 3.0 (interquartile range [IQR], 0.7-11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0-25), and vasoactive-free days were 23 (IQR, 12-28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5-10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,471 [corrected] patients per group. Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted.

Arginase Inhibitor in the Pharmacological Correction of Endothelial Dysfunction

PubMed Central

Pokrovskiy, Mihail V.; Korokin, Mihail V.; Tsepeleva, Svetlana A.; Pokrovskaya, Tatyana G.; Gureev, Vladimir V.; Konovalova, Elena A.; Gudyrev, Oleg S.; Kochkarov, Vladimir I.; Korokina, Liliya V.; Dudina, Eleonora N.; Babko, Anna V.; Terehova, Elena G.

2011-01-01

This paper is about a way of correction of endothelial dysfunction with the inhibitor of arginase: L-norvaline. There is an imbalance between vasoconstriction and vasodilatation factors of endothelium on the basis of endothelial dysfunction. Among vasodilatation agents, nitrogen oxide plays the basic role. Amino acid L-arginine serves as a source of molecules of nitrogen oxide in an organism. Because of the high activity of arginase enzyme which catalyzes the hydrolysis of L-arginine into ornithine and urea, the bioavailability of nitrogen oxide decreases. The inhibitors of arginase suppress the activity of the given enzyme, raising and production of nitrogen oxide, preventing the development of endothelial dysfunction. PMID:21747978

Additional traditional Chinese medicine on gastrointestinal dysfunction in patients with sepsis: A systematic review and meta-analysis.

PubMed

Zhang, Yajing; Zhao, Zhiqiang; Tang, E; Hu, Yucai; Mao, Jingyuan

2016-03-01

To evaluate the clinical effect and safety of western medicine plus Traditional Chinese medicine for sepsis with gastrointestinal dysfunction. We searched CNKI (January 1979 to June 2014), VIP (January 1989 to June 2014), CBM (1978 to 2014), Wan Fang DATA (January 1990 to June 2014), PubMed (1978 to June 2014), The Cochrane Library (Issue 5, 2014), Embase (1974 to June 2014), and other relevant databases and journals to identify randomized controlled trials (RCTs) on western medicine plus Traditional Chinese medicine versus western medicine only for sepsis with gastrointestinal dysfunction. The methodological quality was assessed and the data was extracted according to the Cochrane Reviewer's Handbook and related methods. Meta-analyses were performed by RevMan 5.1.0 software. Five eligible studies included 278 patients. The results of meta-analyses showed that western medicine plus Traditional Chinese medicine therapy can improve the APACHEII score, the peristaltic sound score and SIRS score, improve abdominal distension, decreased white blood cell count, reduce DAO in sepsis patients with gastrointestinal dysfunction. 3 studies reported adverse reactions, there was no significant difference between two groups. Western medicine plus Traditional Chinese medicine can improve gastrointestinal dysfunction in sepsis.

Double valve replacement in a patient with implantable cardioverter defibrillator with severe left ventricular dysfunction.

PubMed

Manjunath, Girish; Rao, Prakash; Prakash, Nagendra; Shivaram, B K

2016-01-01

Recent data from landmark trials suggest that the indications for cardiac pacing and implantable cardioverter defibrillators (ICDs) are set to expand to include heart failure, sleep-disordered breathing, and possibly routine implantation in patients with myocardial infarction and poor ventricular function.[1] This will inevitably result in more patients with cardiac devices undergoing surgeries. Perioperative electromagnetic interference and their potential effects on ICDs pose considerable challenges to the anesthesiologists.[2] We present a case of a patient with automatic ICD with severe left ventricular dysfunction posted for double valve replacement.

Pharmacotherapy for Irritable Bowel Syndrome

PubMed Central

Camilleri, Michael

2017-01-01

Irritable bowel syndrome (IBS) is a disorder of the brain-gut axis; the pathophysiological mechanisms include altered colonic motility, bile acid metabolism, neurohormonal regulation, immune dysfunction, alterations in the epithelial barrier and secretory properties of the gut. This article reviews the mechanisms, efficacy, and safety of current pharmacotherapy, and medications that are in phase III trials for the treatment of IBS. There remains a significant unmet need for effective treatments—particularly for the pain component of IBS—although the introduction of drugs directed at secretion, motility and a non-absorbable antibiotic provide options for the bowel dysfunction in IBS. PMID:29077050

Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis: A Double-Blind, Randomized, Placebo-Controlled Trial.

PubMed

Rassaf, Tienush; Rammos, Christos; Hendgen-Cotta, Ulrike B; Heiss, Christian; Kleophas, Werner; Dellanna, Frank; Floege, Jürgen; Hetzel, Gerd R; Kelm, Malte

2016-01-07

Hemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow-mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)-rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol-rich bioactive food ingredients on acute and chronic HD-induced vascular dysfunction in ESRD. We conducted a randomized, double-blind, placebo-controlled trial from 2012 to 2013. Fifty-seven participants were enrolled, ingested CF-rich beverages (900 mg CF per study day), and were compared with those ingesting CF-free placebo. This included (1) a baseline cross-over acute study to determine safety and efficacy of CF and (2) a subsequent chronic parallel group study with a 30-day follow-up period to study effects of CF on HD-mediated vascular dysfunction entailing (3) an acute substudy during HD in flavanol-naive patients and (4) an acute on chronic study during HD. Primary and secondary outcome measures included changes in FMD and hemodynamics. CF ingestion was well tolerated. Acute ingestion improved FMD by 53% (3.2±0.6% to 4.8±0.9% versus placebo, 3.2±0.7% to 3.3±0.8%; P<0.001), with no effects on BP or heart rate. A 30-day ingestion of CF led to an increase in baseline FMD by 18% (3.4±0.9% to 3.9±0.8% versus placebo, 3.5±0.7% to 3.5±0.7%; P<0.001), with reduced diastolic BP (73±12 to 69±11 mmHg versus placebo, 70±11 to 73±13 mmHg; P=0.03) and increased heart rate (70±12 to 74±13 bpm versus placebo, 75±15 to 74±13 bpm; P=0.01). No effects were observed for placebo. Acute ingestion of CF during HD alleviated HD-induced vascular dysfunction (3.4±0.9% to 2.7±0.6% versus placebo, 3.5±0.7% to 2.0±0.6%; P<0.001). This effect was sustained throughout the study (acute on chronic, 3.9±0.9% to 3.0±0.7% versus placebo, 3.5±0.7% to 2.2±0.6; P=0.01). Dietary CF ingestion mitigates acute HD-induced and chronic endothelial dysfunction in patients with ESRD and thus, improves vascular function in this high-risk population. Larger clinical trials are warranted to test whether this translates into an improved cardiovascular prognosis in patients with ESRD. Copyright © 2016 by the American Society of Nephrology.

Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction.

PubMed

Münzel, Thomas; Steven, Sebastian; Daiber, Andreas

2014-12-01

Given acutely, organic nitrates, such as nitroglycerin (GTN), isosorbide mono- and dinitrates (ISMN, ISDN), and pentaerythrityl tetranitrate (PETN), have potent vasodilator and anti-ischemic effects in patients with acute coronary syndromes, acute and chronic congestive heart failure and arterial hypertension. During long-term treatment, however, side effects such as nitrate tolerance and endothelial dysfunction occur, and therapeutic efficacy of these drugs rapidly vanishes. Recent experimental and clinical studies have revealed that organic nitrates per se are not just nitric oxide (NO) donors, but rather a quite heterogeneous group of drugs considerably differing for mechanisms underlying vasodilation and the development of endothelial dysfunction and tolerance. Based on this, we propose that the term nitrate tolerance should be avoided and more specifically the terms of GTN, ISMN and ISDN tolerance should be used. The present review summarizes preclinical and clinical data concerning organic nitrates. Here we also emphasize the consequences of chronic nitrate therapy on the supersensitivity of the vasculature to vasoconstriction and on the increased autocrine expression of endothelin. We believe that these so far rather neglected and underestimated side effects of chronic therapy with at least GTN and ISMN are clinically important. Copyright © 2014 Elsevier Inc. All rights reserved.

A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-12-1-0543 TITLE: A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism ...Therapy for Autism Spectrum Disorder 5b. GRANT NUMBER W81XWH-12-1-0543 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) John Gabrieli, Ph.D; Aude Henin...core social dysfunctions, and (2) oxytocin (OT) administration prior to CBT sessions will each enhance social function in young adults with autism

A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management.

PubMed

Grossmann, Mathis; Matsumoto, Alvin M

2017-03-01

Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic-pituitary-testicular axis pathology but have functional hypogonadism that is potentially reversible. Literature review from 1970 to October 2016. Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency-like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy.

[Advances in arterial hypertension and diabetes mellitus].

PubMed

Cordero, Alberto; Lekuona, Iñaki; Galve, Enrique; Mazón, Pilar

2012-01-01

In 2011, the importance of hypertension and diabetes mellitus as the two main risk factors responsible for the development of cardiovascular disease became clear, as did their significance as major public health issues. Compared with previous years, in which publication of the results of large clinical trials dominated scientific progress, in the last year, the focus has shifted to evidence that novel mechanisms associated with blood pressure, glucose metabolism and diabetes can influence cardiovascular disease. Of particular importance were clinical trials in the area of renal dysfunction, such as the SHARP and ROADMAP trials. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Effect of chewing gum on the postoperative recovery of gastrointestinal function

PubMed Central

Ge, Wei; Chen, Gang; Ding, Yi-Tao

2015-01-01

Postoperative gastrointestinal dysfunction remains a source of morbidity and the major determinant of length of stay after abdominal operation. There are many different reasons for postoperative gastrointestinal dysfunction such as stress response, perioperative interventions, bowel manipulation and so on. The mechanism of enhanced recovery from postoperative gastrointestinal dysfunction with the help of chewing gum is believed to be the cephalic-vagal stimulation of digestion which increases the promotability of neural and humoral factors that act on different parts of the gastrointestinal tract. Recently, there were a series of randomized controlled trials to confirm the role of chewing gum in the recovery of gastrointestinal function. The results suggested that chewing gum enhanced early recovery of bowel function following abdominal surgery expect the gastrointestinal surgery. However, the effect of chewing gum in gastrointestinal surgery was controversial. PMID:26550107

Ammonia toxicity: from head to toe?

PubMed

Dasarathy, Srinivasan; Mookerjee, Rajeshwar P; Rackayova, Veronika; Rangroo Thrane, Vinita; Vairappan, Balasubramaniyan; Ott, Peter; Rose, Christopher F

2017-04-01

Ammonia is diffused and transported across all plasma membranes. This entails that hyperammonemia leads to an increase in ammonia in all organs and tissues. It is known that the toxic ramifications of ammonia primarily touch the brain and cause neurological impairment. However, the deleterious effects of ammonia are not specific to the brain, as the direct effect of increased ammonia (change in pH, membrane potential, metabolism) can occur in any type of cell. Therefore, in the setting of chronic liver disease where multi-organ dysfunction is common, the role of ammonia, only as neurotoxin, is challenged. This review provides insights and evidence that increased ammonia can disturb many organ and cell types and hence lead to dysfunction.

Addressing sexual dysfunction after risk-reducing salpingo-oophorectomy: effects of a brief, psychosexual intervention.

PubMed

Bober, Sharon L; Recklitis, Christopher J; Bakan, Jennifer; Garber, Judy E; Patenaude, Andrea F

2015-01-01

Women at high risk for ovarian cancer due to BRCA1 or BRCA2 mutation or family history are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) after age 35 or completion of childbearing. This potentially life-saving surgery leads to premature menopause, frequently resulting in distressing and unaddressed sexual dysfunction. To pilot a novel sexual health intervention for women with BRCA1/2 mutations who previously underwent RRSO a using a single-arm trial. Feasibility and primary outcomes including sexual dysfunction and psychological distress were assessed. This single-arm trial included a one-time, half-day educational session comprised of targeted sexual health education, body awareness and relaxation training, and mindfulness-based cognitive therapy strategies, followed by two sessions of tailored telephone counseling. Assessments were completed at baseline and 2 months postintervention. Study end points include feasibility and effectiveness as reported by the participant. Thirty-seven women completed baseline and postintervention assessments. At baseline, participants had a mean age of 44.4 (standard deviation [SD] = 3.9) years and mean duration of 3.8 (SD = 2.7) years since RRSO. Overall sexual functioning (P = 0.018), as well as desire (P = 0.003), arousal (P = 0.003), satisfaction (P = 0.028), and pain (P = 0.018), improved significantly. There were significant reductions in somatization (P = 0.029) and anxiety scores (P < 0.001), and, overall, for the Global Severity Index (P < 0.001) of the Brief Symptom Inventory. Sexual self-efficacy and sexual knowledge also improved significantly from baseline to postintervention (both P < 0.001). Women were highly satisfied with the intervention content and reported utilizing new skills to manage sexual dysfunction. This intervention integrates elements of cognitive behavioral therapy with sexual health education to address a much-neglected problem after RRSO. Results from this promising single-arm study provide preliminary data to move toward conducting a randomized, controlled trial. © 2014 International Society for Sexual Medicine.

New insights into bioactivation of organic nitrates, nitrate tolerance and cross-tolerance.

PubMed

Daiber, A; Wenzel, P; Oelze, M; Münzel, T

2008-01-01

Organic nitrates still represent a group of very effective anti-ischemic drugs used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. Long-term therapy with organic nitrates, however, results in a rapid development of nitrate tolerance blunting their hemodynamic and antiischemic efficacy. Recent studies revealed that mitochondrial reactive oxygen species (ROS) formation and a subsequent oxidative inactivation of nitrate reductase, the mitochondrial aldehyde dehydrogenase (ALDH-2), play an important role for the development of nitrate and crosstolerance. The present review focuses firstly on the role of ALDH-2 for organic nitrate bioactivation and secondly on the role of oxidative stress in the development of tolerance and cross-tolerance (endothelial dysfunction) in response to various organic nitrates. Finally, we would like to draw the reader's attention to the protective properties of the organic nitrate pentaerithrityl tetranitrate (PETN), which, in contrast to all other organic nitrates, is able to upregulate enzymes with a strong antioxidative capacity thereby preventing tolerance and the development of endothelial dysfunction.

Exercise Training for Heart Failure Patients with and without Systolic Dysfunction: An Evidence-Based Analysis of How Patients Benefit

PubMed Central

Smart, Neil

2011-01-01

Significant benefits can be derived by heart failure patients from exercise training. This paper provides an evidence-based assessment of expected clinical benefits of exercise training for heart failure patients. Meta-analyses and randomized, controlled trials of exercise training in heart failure patients were reviewed from a search of PubMed, Cochrane Controlled Trial Registry (CCTR), CINAHL, and EMBASE. Exercise training improves functional capacity, quality of life, hospitalization, and systolic and diastolic function in heart failure patients. Heart failure patients with preserved systolic function (HFnEF) participating in exercise training studies are more likely to be women and are 5–7 years older than their systolic heart failure (CHF) counterparts. All patients exhibit low functional capacities, although in HFnEF patients this may be age related, therefore subtle differences in exercise prescriptions are required. Published works report that exercise training is beneficial for heart failure patients with and without systolic dysfunction. PMID:20953365

The effectiveness of a Group Triple P with Chinese parents who have a child with developmental disabilities: a randomized controlled trial.

PubMed

Leung, Cynthia; Fan, Angel; Sanders, Matthew R

2013-03-01

The study examined the effectiveness of Group Triple P, a Level 4 variant of the Triple P multilevel system of parenting support, with Chinese parents who had a preschool aged child with a developmental disability, using randomized controlled trial design. Participants (Intervention group: 42; Waitlist Control group: 39) completed measures on child behaviour, parental stress, dysfunctional discipline styles and parental conflict before and after program completion by the Intervention group. Intervention group participants also completed these same measures six months after program completion. Compared to the Waitlist Control group, parents receiving Group Triple P reported significantly lower levels of child behaviour problems, parental stress, dysfunctional discipline style and parental conflict scores. The Intervention group participants maintained their gains six months after program completion. The results provided promising evidence for the Level 4 Group Triple P as an effective intervention program for Chinese parents who have preschool aged children with developmental disabilities. Copyright © 2012 Elsevier Ltd. All rights reserved.

Therapeutic progress in amyotrophic lateral sclerosis-beginning to learning.

PubMed

Kumar, Vijay; Islam, Asimul; Hassan, Md Imtaiyaz; Ahmad, Faizan

2016-10-04

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle weakness, paralysis and finally death. The proposed mechanisms of ALS include glutamate excitotoxicity, oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and proteasomal dysfunction. Although numerous pathological mechanisms have been explained, ALS remains incurable disease because of failure of clinical trials and lack of any effective therapy. The rapid advancement in genetic discoveries in ALS emphasizes the point that ALS is a multi-subtype syndrome rather than a single disease. This can be argued as one of the single reason why many previous therapeutic drug trials have failed. Efforts to develop novel ALS treatments which target specific pathomechanisms are currently being pursued. Herein, we review the recent discovery and preclinical characterization of neuroprotective compounds and compare their effects on disease onset, duration and survival. Furthermore, the structure-activity relationships of these agents are analyzed with the overall goal of developing a screening strategy for future clinical applications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The use of the sexual function questionnaire as a screening tool for women with sexual dysfunction.

PubMed

Quirk, Frances; Haughie, Scott; Symonds, Tara

2005-07-01

To determine if the validated Sexual Function Questionnaire (SFQ), developed to assess efficacy in female sexual dysfunction (FSD) clinical trials, may also have utility in identifying target populations for such studies. Data from five clinical trials and two general population surveys were used to analyze the utility of the SFQ as a tool to discriminate between the presence of specific components of FSD (i.e., hypoactive sexual desire disorder, female sexual arousal disorder, female orgasmic disorder, and dyspareunia). Sensitivity/specificity analysis and logistic regression analysis, using data from all five clinical studies and the general population surveys, confirmed that the SFQ domains have utility in detecting the presence of specific components of FSD and provide scores indicative of the presence of a specific sexual disorder. The SFQ is a valuable new tool for detecting the presence of FSD and identifying the specific components of sexual functions affected (desire, arousal, orgasm, or dyspareunia).

Light Chain Amyloidosis

PubMed Central

Milani, Paolo; Merlini, Giampaolo

2018-01-01

Light chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic light chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by the response to therapy. The specific treatment is chemotherapy targeting the underlying plasma-cell clone. It needs to be risk-adapted, according to the severity of cardiac and/or multi-organ involvement. Autologous stem cell transplant (preceded by induction and/or followed by consolidation with bortezomib-based regimens) can be considered for low-risk patients (~20%). Bortezomib combined with alkylators is used in the majority of intermediate-risk patients, and with possible dose escalation in high-risk subjects. Novel, powerful anti-plasma cell agents were investigated in the relapsed/refractory setting, and are being moved to upfront therapy in clinical trials. In addition, the use of novel approaches based on antibodies targeting the amyloid deposits or small molecules interfering with the amyloidogenic process gave promising results in preliminary studies. Some of them are under evaluation in controlled trials. These molecules will probably add powerful complements to standard chemotherapy. The understanding of the specific molecular mechanisms of cardiac damage and the characteristics of the amyloidogenic clone are unveiling novel potential treatment approaches, moving towards a cure for this dreadful disease. PMID:29531659

Cognitive remission: a novel objective for the treatment of major depression?

PubMed

Bortolato, Beatrice; Miskowiak, Kamilla W; Köhler, Cristiano A; Maes, Michael; Fernandes, Brisa S; Berk, Michael; Carvalho, André F

2016-01-22

Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.

Treating the dysfunctional placenta

PubMed Central

2017-01-01

Placental dysfunction underlies major obstetric diseases such as pre-eclampsia and fetal growth restriction (FGR). Whilst there has been a little progress in prophylaxis, there are still no treatments for placental dysfunction in normal obstetric practice. However, a combination of increasingly well-described in vitro systems for studying the human placenta, together with the availability of more appropriate animal models of pre-eclampsia and FGR, has facilitated a recent surge in work aimed at repurposing drugs and therapies, developed for other conditions, as treatments for placental dysfunction. This review: (1) highlights potential candidate drug targets in the placenta – effectors of improved uteroplacental blood flow, anti-oxidants, heme oxygenase induction, inhibition of HIF, induction of cholesterol synthesis pathways, increasing insulin-like growth factor II availability; (2) proposes an experimental pathway for taking a potential drug or treatment for placental dysfunction from concept through to early phase clinical trials, utilizing techniques for studying the human placenta in vitro and small animal models, particularly the mouse, for in vivo studies; (3) describes the data underpinning sildenafil citrate and adenovirus expressing vascular endothelial growth as potential treatments for placental dysfunction and summarizes recent research on other potential treatments. The importance of sharing information from such studies even when no effect is found, or there is an adverse outcome, is highlighted. Finally, the use of adenoviral vectors or nanoparticle carriers coated with homing peptides to selectively target drugs to the placenta is highlighted: such delivery systems could improve efficacy and reduce the side effects of treating the dysfunctional placenta. PMID:28483805

Cardiac Dysfunction and Oxidative Stress in the Metabolic Syndrome: an Update on Antioxidant Therapies

PubMed Central

Ilkun, Olesya; Boudina, Sihem

2013-01-01

The metabolic syndrome (MetS) is a cluster of risk factors including obesity, insulin resistance, dyslipidemia, elevated blood pressure and glucose intolerance. The MetS increases the risk for cardiovascular disease (CVD) and type 2 diabetes. Each component of the MetS causes cardiac dysfunction and their combination carries additional risk. The mechanisms underlying cardiac dysfunction in the MetS are complex and might include lipid accumulation, increased fibrosis and stiffness, altered calcium homeostasis, abnormal autophagy, altered substrate utilization, mitochondrial dysfunction and increased oxidative stress. Mitochondrial and extra-mitochondrial sources of reactive oxygen species (ROS) and reduced antioxidant defense mechanisms characterize the myocardium of humans and animals with the MetS. The mechanisms for increased cardiac oxidative stress in the MetS are not fully understood but include increased fatty acid oxidation, mitochondrial dysfunction and enhanced NADPH oxidase activity. Therapies aimed to reduce oxidative stress and enhance antioxidant defense have been employed to reduce cardiac dysfunction in the MetS in animals. In contrast, large scale clinical trials using antioxidants therapies for the treatment of CVD have been disappointing because of the lack of efficacy and undesired side effects. The focus of this review is to summarize the current knowledge about the mechanisms underlying cardiac dysfunction in the MetS with a special interest in the role of oxidative stress. Finally, we will update the reader on the results obtained with natural antioxidant and mitochondria-targeted antioxidant therapies for the treatment of CVD in the MetS. PMID:23323621

Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances

PubMed Central

Iacoviello, Massimo; Leone, Marta; Antoncecchi, Valeria; Ciccone, Marco Matteo

2015-01-01

Chronic kidney disease and its worsening are recurring conditions in chronic heart failure (CHF) which are independently associated with poor patient outcome. The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index (a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction. PMID:25610846

Sequential N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin Measurements During Albumin Replacement in Patients With Severe Sepsis or Septic Shock.

PubMed

Masson, Serge; Caironi, Pietro; Fanizza, Caterina; Carrer, Sara; Caricato, Anselmo; Fassini, Paola; Vago, Tarcisio; Romero, Marilena; Tognoni, Gianni; Gattinoni, Luciano; Latini, Roberto

2016-04-01

Myocardial dysfunction is a frequent complication in patients with severe sepsis and can worsen the prognosis. We investigated whether circulating biomarkers related to myocardial function and injury predicted outcome and were associated with albumin replacement. A multicenter, randomized clinical trial about albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis trial). Forty ICUs in Italy. Nine hundred and ninety-five patients with severe sepsis or septic shock. Randomization to albumin and crystalloid solutions or crystalloid solutions alone. Plasma concentrations of N- terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T were measured 1, 2, and 7 days after enrollment. We tested the relationship of single marker measurements or changes over time with clinical events, organ dysfunctions, albumin replacement, and ICU or 90-day mortality in the overall population and after stratification by shock. N-terminal pro-B-type natriuretic peptide levels were abnormal in 97.4% of the patients and high-sensitivity cardiac troponin T in 84.5%, with higher concentrations in those with shock. After extensive adjustments, N-terminal pro-B-type natriuretic peptide concentrations predicted ICU or 90-day mortality, better than high-sensitivity cardiac troponin T. Early changes in N-terminal pro-B-type natriuretic peptide or high-sensitivity cardiac troponin T concentrations were independently associated with subsequent mortality in patients with shock. Patients given albumin had significantly higher N-terminal pro-B-type natriuretic peptide levels; in addition, early rise in N-terminal pro-B-type natriuretic peptide was associated with a better outcome in this subgroup. Circulating N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T are frequently elevated in severe sepsis or septic shock and have relevant prognostic value, which may be important in monitoring the clinical efficacy of supporting therapy.

Albumin replacement in patients with severe sepsis or septic shock.

PubMed

Caironi, Pietro; Tognoni, Gianni; Masson, Serge; Fumagalli, Roberto; Pesenti, Antonio; Romero, Marilena; Fanizza, Caterina; Caspani, Luisa; Faenza, Stefano; Grasselli, Giacomo; Iapichino, Gaetano; Antonelli, Massimo; Parrini, Vieri; Fiore, Gilberto; Latini, Roberto; Gattinoni, Luciano

2014-04-10

Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P=0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P=0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P=0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P=0.29). No significant differences in other secondary outcomes were observed between the two groups. In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.).

Student Leadership in a Residential College: From Dysfunction to Effective Collaboration

ERIC Educational Resources Information Center

Bloomdahl, Susana Contreras; Navan, Joy

2013-01-01

This article depicts the intervention strategy of two faculty members on a dysfunctional student council in a residential college setting. The council demonstrated poor collaboration and productivity, which indicated signs of distrust. The group intervention helped to expose the students' lack of organization and need to learn more about each…

Aminoethyl nitrate – the novel super nitrate?

PubMed Central

Bauersachs, Johann

2009-01-01

Long-term use of most organic nitrates is limited by development of tolerance, induction of oxidative stress and endothelial dysfunction. In this issue of the BJP, Schuhmacher et al. characterized a novel class of organic nitrates with amino moieties (aminoalkyl nitrates). Aminoethyl nitrate was identified as a novel organic mononitrate with high potency but devoid of induction of mitochondrial oxidative stress. Cross-tolerance to nitroglycerin or the endothelium-dependent agonist acetylcholine after in vivo treatment was not observed. Like all nitrates, aminoethyl nitrate induced vasorelaxation by activation of soluble guanylate cyclase. Thus, in contrast to the prevailing view, high potency in an organic nitrate is not necessarily accompanied by induction of oxidative stress or endothelial dysfunction. This work from Daiber's group is an important step forward in the understanding of nitrate bioactivation, tolerance phenomena and towards the development of better organic nitrates for clinical use. PMID:19732062

Metformin effects on the heart and the cardiovascular system: A review of experimental and clinical data.

PubMed

Nesti, L; Natali, A

2017-08-01

Metformin, the eldest and most widely used glucose lowering drug, is likely to be effective also on cardiac and vascular disease prevention. Nonetheless, uncertainty still exists with regard to its effects on the cardiovascular system as a whole and specifically on the myocardium, both at the organ and cellular levels. We reviewed the available data on the cardiac and vascular effects of metformin, encompassing both in vitro, either tissue or isolated organ, and in vivo studies in experimental animals and humans, as well as the evidence generated by major clinical trials. At the cellular level metformin's produces both AMP-activated kinase (AMPK) dependent and independent effects. At the systemic level, possibly also through other pathways, this drug improves endothelial function, protects from oxidative stress and inflammation, and from the negative effects of angiotensin II. On the myocardium it attenuates ischemia-reperfusion injury and prevents adverse remodeling induced by humoral and hemodynamic factors. The effects on myocardial cell metabolism and contractile function being not evident at rest or in more advanced stages of cardiac dysfunction, could be relevant during transient ischemia, during an acute increase in workload and in the early stages of diabetic/hypertensive cardiomyopathy as confirmed by few small clinical trials and some observational studies. The overall evidence emerging from both clinical trials and real world registry is in favor of a protective effect of metformin with respect to both coronary events and progression to heart failure. Given this potential, its efficacy and its safety (and also its low cost) metformin remains the central pillar of the therapy of diabetes. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

The outcomes and prognostic factors of acute respiratory failure in the patients 90 years old and over

PubMed Central

Kung, Shu-Chen; Wang, Ching-Min; Lai, Chih-Cheng; Chao, Chien-Ming

2018-01-01

This retrospective cohort study investigated the outcomes and prognostic factors in nonagenarians (patients 90 years old or older) with acute respiratory failure. Between 2006 and 2016, all nonagenarians with acute respiratory failure requiring invasive mechanical ventilation (MV) were enrolled. Outcomes including in-hospital mortality and ventilator dependency were measured. A total of 173 nonagenarians with acute respiratory failure were admitted to the intensive care unit (ICU). A total of 56 patients died during the hospital stay and the rate of in-hospital mortality was 32.4%. Patients with higher APACHE (Acute Physiology and Chronic Health Evaluation) II scores (adjusted odds ratio [OR], 5.91; 95 % CI, 1.55-22.45; p = 0.009, APACHE II scores ≥ 25 vs APACHE II scores < 15), use of vasoactive agent (adjust OR, 2.67; 95% CI, 1.12-6.37; p = 0.03) and more organ dysfunction (adjusted OR, 11.13; 95% CI, 3.38-36.36, p < 0.001; ≥ 3 organ dysfunction vs ≤ 1 organ dysfunction) were more likely to die. Among the 117 survivors, 25 (21.4%) patients became dependent on MV. Female gender (adjusted OR, 3.53; 95% CI, 1.16-10.76, p = 0.027) and poor consciousness level (adjusted OR, 4.98; 95% CI, 1.41-17.58, p = 0.013) were associated with MV dependency. In conclusion, the mortality rate of nonagenarians with acute respiratory failure was high, especially for those with higher APACHE II scores or more organ dysfunction. PMID:29467961

Contemporary Patterns of Multiple Organ Dysfunction in Trauma.

PubMed

Shepherd, Joanna M; Cole, Elaine; Brohi, Karim

2017-04-01

Multiple organ dysfunction syndrome (MODS) is associated with poor outcomes for trauma patients. Different forms of MODS may exist and have different consequences. The ability to distinguish them clinically may have implications for prognosis and treatment. We wished to study whether prolonged MODS (PRMODS) could be observed as a distinct clinical entity to early resolving MODS (ERMODS) in critically injured patients. Adult major trauma patients recruited to a prospective observational study at a single major trauma center were eligible for inclusion. MODS was defined as Sequential Organ Failure Assessment (SOFA) score >5; and PRMODS as lasting >7 days. Time to recovery (TTR) was calculated as the number of days before the SOFA fell below the MODS threshold (≤5). Five hundred ninety-five patients were enrolled of whom 285 developed ERMODS (48%) and 184 (31%) PRMODS. Organ dysfunction was more severe and protracted in PRMODS, especially in patients without brain injury (mean SOFA 11 vs. 6, Day 2, P < 0.001; TTR 17 vs. 3 days, P < 0.001). PRMODS exhibited higher rates of hepatic and renal dysfunction (84% vs. 56%; and 78% vs. 47%, P≤0.001). Patterns of recovery were distinct in hepatic, renal, and neurological systems (TTR 15 vs. 4; 20 vs. 3; and 28 vs. 7 days, P < 0.01). PRMODS was associated with higher infection and mortality rates (91% vs. 41%; and 22% vs. 7%, P < 0.001). PRMODS appears common, a distinct clinical entity, and associated with worse patient outcomes. PRMODS may represent an important endpoint for studies evaluating outcomes following trauma.

Association between length of storage of red blood cell units and outcome of critically ill children: a prospective observational study

PubMed Central

2010-01-01

Introduction Transfusion is a common treatment in pediatric intensive care units (PICUs). Studies in adults suggest that prolonged storage of red blood cell units is associated with worse clinical outcome. No prospective study has been conducted in children. Our objectives were to assess the clinical impact of the length of storage of red blood cell units on clinical outcome of critically ill children. Methods Prospective, observational study conducted in 30 North American centers, in consecutive patients aged <18 years with a stay ≥ 48 hours in a PICU. The primary outcome measure was the incidence of multiple organ dysfunction syndrome after transfusion. The secondary outcomes were 28-day mortality and PICU length of stay. Odds ratios were adjusted for gender, age, number of organ dysfunctions at admission, total number of transfusions, and total dose of transfusion, using a multiple logistic regression model. Results The median length of storage was 14 days in 296 patients with documented length of storage. For patients receiving blood stored ≥ 14 days, the adjusted odds ratio for an increased incidence of multiple organ dysfunction syndrome was 1.87 (95% CI 1.04;3.27, P = 0.03). There was also a significant difference in the total PICU length of stay (adjusted median difference +3.7 days, P < 0.001) and no significant change in mortality. Conclusions In critically ill children, transfusion of red blood cell units stored for ≥ 14 days is independently associated with an increased occurrence of multiple organ dysfunction syndrome and prolonged PICU stay. PMID:20377853

Identifying Pediatric Severe Sepsis and Septic Shock: Accuracy of Diagnosis Codes.

PubMed

Balamuth, Fran; Weiss, Scott L; Hall, Matt; Neuman, Mark I; Scott, Halden; Brady, Patrick W; Paul, Raina; Farris, Reid W D; McClead, Richard; Centkowski, Sierra; Baumer-Mouradian, Shannon; Weiser, Jason; Hayes, Katie; Shah, Samir S; Alpern, Elizabeth R

2015-12-01

To evaluate accuracy of 2 established administrative methods of identifying children with sepsis using a medical record review reference standard. Multicenter retrospective study at 6 US children's hospitals. Subjects were children >60 days to <19 years of age and identified in 4 groups based on International Classification of Diseases, Ninth Revision, Clinical Modification codes: (1) severe sepsis/septic shock (sepsis codes); (2) infection plus organ dysfunction (combination codes); (3) subjects without codes for infection, organ dysfunction, or severe sepsis; and (4) infection but not severe sepsis or organ dysfunction. Combination codes were allowed, but not required within the sepsis codes group. We determined the presence of reference standard severe sepsis according to consensus criteria. Logistic regression was performed to determine whether addition of codes for sepsis therapies improved case identification. A total of 130 out of 432 subjects met reference SD of severe sepsis. Sepsis codes had sensitivity 73% (95% CI 70-86), specificity 92% (95% CI 87-95), and positive predictive value 79% (95% CI 70-86). Combination codes had sensitivity 15% (95% CI 9-22), specificity 71% (95% CI 65-76), and positive predictive value 18% (95% CI 11-27). Slight improvements in model characteristics were observed when codes for vasoactive medications and endotracheal intubation were added to sepsis codes (c-statistic 0.83 vs 0.87, P = .008). Sepsis specific International Classification of Diseases, Ninth Revision, Clinical Modification codes identify pediatric patients with severe sepsis in administrative data more accurately than a combination of codes for infection plus organ dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis.

PubMed

Weiss, Scott L; Fitzgerald, Julie C; Balamuth, Fran; Alpern, Elizabeth R; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert; Nadkarni, Vinay M; Thomas, Neal J

2014-11-01

Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock. Retrospective observational study. PICU at an academic medical center. One hundred thirty patients treated for severe sepsis or septic shock. None. We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure-free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74-277 min) and to first appropriate antimicrobial was 177 minutes (90-550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27-12.06) and 3.59 (95% CI, 1.09-11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45-16.2) and 4.92 (95% CI, 1.30-18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure-free days (16 [interquartile range, 1-23] vs 20 [interquartile range, 6-26]; p = 0.04). Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.

Delayed Antimicrobial Therapy Increases Mortality and Organ Dysfunction Duration in Pediatric Sepsis

PubMed Central

Weiss, Scott L.; Fitzgerald, Julie C.; Balamuth, Fran; Alpern, Elizabeth R.; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert; Nadkarni, Vinay M.; Thomas, Neal J.

2014-01-01

Objectives Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock. Design Retrospective observational study. Setting PICU at an academic medical center. Patients One hundred thirty patients treated for severe sepsis or septic shock. Interventions None. Measurements and Main Results We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure–free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74–277 min) and to first appropriate antimicrobial was 177 minutes (90–550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27–12.06) and 3.59 (95% CI, 1.09–11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45–16.2) and 4.92 (95% CI, 1.30–18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure–free days (16 [interquartile range, 1–23] vs 20 [interquartile range, 6–26]; p = 0.04). Conclusions Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis. PMID:25148597

Effect of postpartum pelvic floor muscle training on vaginal symptoms and sexual dysfunction-secondary analysis of a randomised trial.

PubMed

Kolberg Tennfjord, M; Hilde, G; Staer-Jensen, J; Siafarikas, F; Engh, M Ellström; Bø, K

2016-03-01

Evaluate effect of pelvic floor muscle training (PFMT) on vaginal symptoms and sexual matters, dyspareunia and coital incontinence in primiparous women stratified by major or no defects of the levator ani muscle. Randomised controlled trial (RCT). Akershus University Hospital, Norway. About 175 primiparous women with a singleton vaginal delivery. Two-armed assessor blinded parallel group RCT from 6 weeks to 6 months postpartum comparing effect of PFMT versus control. International Consultation on Incontinence Modular Questionnaire-vaginal symptoms questionnaire (ICIQ-VS) and ICIQ sexual matters module (ICIQ-FLUTSsex). Overall, analysis (n = 175) showed no difference between training and control groups in women having vaginal symptoms or symptoms related to sexual dysfunction 6 months postpartum. The majority of women (88%) had intercourse and there was no difference between groups. Unadjusted subgroup analysis of women with a major defect of the levator ani muscle (n = 55) showed that women in the training group had 45% less risk of having the symptom 'vagina feels loose or lax' compared with the control group (relative risk 0.55, 95% confidence interval 0.31, 0.95; P = 0.03). Unadjusted analysis showed that in women with major defect of the levator ani muscle, significantly fewer in the training group had the symptom 'vagina feels loose or lax' compared with the control group. No difference was found between groups for symptoms related to sexual dysfunction. More studies are needed to explore effect of PFMT on vaginal symptoms and sexual dysfunction. Unadjusted analysis shows that PFMT might prevent symptoms of 'vagina feels loose or lax'. © 2015 Royal College of Obstetricians and Gynaecologists.

Novel Oral Therapies for Opioid-induced Bowel Dysfunction in Patients with Chronic Noncancer Pain.

PubMed

Holder, Renee M; Rhee, Diane

2016-03-01

Opioid analgesics are frequently prescribed and play an important role in chronic pain management. Opioid-induced bowel dysfunction, which includes constipation, hardened stool, incomplete evacuation, gas, and nausea and vomiting, is the most common adverse event associated with opioid use. Mu-opioid receptors are specifically responsible for opioid-induced bowel dysfunction, resulting in reduced peristaltic and secretory actions. Agents that reverse these actions in the bowel without reversing pain control in the central nervous system may be preferred over traditional laxatives. The efficacy and safety of these agents in chronic noncancer pain were assessed from publications identified through Ovid and PubMed database searches. Trials that evaluated the safety and efficacy of oral agents for opioid-induced constipation or opioid-induced bowel dysfunction, excluding laxatives, were reviewed. Lubiprostone and naloxegol are approved in the United States by the Food and Drug Administration for use in opioid-induced constipation. Axelopran (TD-1211) and sustained-release naloxone have undergone phase 2 and phase 1 studies, respectively, for the same indication. Naloxegol and axelopran are peripherally acting μ-opioid receptor antagonists. Naloxone essentially functions as a peripherally acting μ-opioid receptor antagonist when administered orally in a sustained-release formulation. Lubiprostone is a locally acting chloride channel (CIC-2) activator that increases secretions and peristalsis. All agents increase spontaneous bowel movements and reduce other bowel symptoms compared with placebo in patients with noncancer pain who are chronic opioid users. The most common adverse events were gastrointestinal in nature, and none of the drugs were associated with severe adverse or cardiovascular events. Investigations comparing these agents to regimens using standard laxative and combination therapy and trials in special populations and patients with active cancer are needed to further define their role in therapy. © 2016 Pharmacotherapy Publications, Inc.

Controlled randomized clinical trial of spirituality integrated psychotherapy, cognitive-behavioral therapy and medication intervention on depressive symptoms and dysfunctional attitudes in patients with dysthymic disorder

PubMed Central

Ebrahimi, Amrollah; Neshatdoost, Hamid Taher; Mousavi, Seyed Ghafur; Asadollahi, Ghorban Ali; Nasiri, Hamid

2013-01-01

Background: Due to the controversy over efficacy of cognitive-behavioral therapy for chronic depression, recently, there has been an increasingly tendency toward therapeutic methods based on the cultural and spiritual approaches. The aim of this research was to compare efficacy of spiritual integrated psychotherapy (SIPT) and cognitive-behavioral therapy (CBT) on the intensity of depression symptoms and dysfunctional attitudes of patients with dysthymic disorder. Materials and Methods: This study had a mixed qualitative and quantitative design. In the first phase, SIPT model was prepared and, in the second phase, a double-blind random clinical trial was performed. Sixty-two patients with dysthymic disorder were selected from several centers include Nour and Alzahra Medical Center, Counseling Centers of Isfahan University of Medical Sciences and Goldis in Isfahan. The participants were randomly assigned to three experimental groups and one control group. The first group received 8 sessions treatment of SIPT, second groups also had 8 sessions of cognitive-behavioral therapy, which was specific to dysthymic disorder and third group were under antidepressant treatment. Beck depression inventory and dysfunctional attitudes scale were used to evaluate all the participants in four measurement stages. The data were analyzed using MANCOVA repeated measure method. Results: The results revealed that SIPT had more efficacy than medication based on both scales (P < 0.01); however, it was not different from CBT. SIPT was more effective on the modification of dysfunctional attitudes compared with CBT and medication (P < 0.05). Conclusion: These findings supported the efficacy of psychotherapy enriched with cultural capacities and religious teachings. PMID:24516853

Sexual dysfunction in premenopausal women could be related to hormonal profile.

PubMed

Vale, Fabiene Bernardes Castro; Coimbra, Bruna Barbosa; Lopes, Gerson Pereira; Geber, Selmo

2017-02-01

Female sexual dysfunction (FSD) is a public health problem that affects women's quality of life. Although the relationship between some hormones and the FSD has been described, it is not well established for all hormones. Therefore, the aim of our study was to evaluate the association between hormonal dysfunction and sexual dysfunction in premenopausal women. We performed a cross-sectional study with 60 patients with regular menstrual cycles, with age ranging from 18 to 44 years, with previous diagnosis of FSD. All patients were evaluated using the female sexual function index (FSFI) questionnaire and had the levels of total testosterone, prolactin (PRL), thyroid-releasing hormone and free testosterone index measured. Among the 60 patients, 43 (71.7%) were diagnosed with hypoactive sexual desire disorder (HSDD), 9 (15%) had anorgasmy and 8 (3.3%) had sexual pain dysfunction. Hormonal evaluation, demonstrated that 79.1% of patients with HSDD, 78.4% of patients with anorgasmy and 50% of patients with sexual pain dysfunction had female androgen insensitivity. We can conclude that there is an important association between low levels of total and free testosterone and FSD. This finding offers a new alternative for diagnosis and treatment of HSDD. Moreover, given the potential role of androgens in sexual function, randomized controlled trials with adequate long-term follow-up are essential to confirm its possible effect.

A rational approach to fluid therapy in sepsis.

PubMed

Marik, P; Bellomo, R

2016-03-01

Aggressive fluid resuscitation to achieve a central venous pressure (CVP) greater than 8 mm Hg has been promoted as the standard of care, in the management of patients with severe sepsis and septic shock. However recent clinical trials have demonstrated that this approach does not improve the outcome of patients with severe sepsis and septic shock. Pathophysiologically, sepsis is characterized by vasoplegia with loss of arterial tone, venodilation with sequestration of blood in the unstressed blood compartment and changes in ventricular function with reduced compliance and reduced preload responsiveness. These data suggest that sepsis is primarily not a volume-depleted state and recent evidence demonstrates that most septic patients are poorly responsive to fluids. Furthermore, almost all of the administered fluid is sequestered in the tissues, resulting in severe oedema in vital organs and, thereby, increasing the risk of organ dysfunction. These data suggest that a physiologic, haemodynamically guided conservative approach to fluid therapy in patients with sepsis would be prudent and would likely reduce the morbidity and improve the outcome of this disease. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue

PubMed Central

Boengler, Kerstin; Kosiol, Maik; Mayr, Manuel; Schulz, Rainer

2017-01-01

Abstract Age is the most important risk factor for most diseases. Mitochondria play a central role in bioenergetics and metabolism. In addition, several lines of evidence indicate the impact of mitochondria in lifespan determination and ageing. The best‐known hypothesis to explain ageing is the free radical theory, which proposes that cells, organs, and organisms age because they accumulate reactive oxygen species (ROS) damage over time. Mitochondria play a central role as the principle source of intracellular ROS, which are mainly formed at the level of complex I and III of the respiratory chain. Dysfunctional mitochondria generating less ATP have been observed in various aged organs. Mitochondrial dysfunction comprises different features including reduced mitochondrial content, altered mitochondrial morphology, reduced activity of the complexes of the electron transport chain, opening of the mitochondrial permeability transition pore, and increased ROS formation. Furthermore, abnormalities in mitochondrial quality control or defects in mitochondrial dynamics have also been linked to senescence. Among the tissues affected by mitochondrial dysfunction are those with a high‐energy demand and thus high mitochondrial content. Therefore, the present review focuses on the impact of mitochondria in the ageing process of heart and skeletal muscle. In this article, we review different aspects of mitochondrial dysfunction and discuss potential therapeutic strategies to improve mitochondrial function. Finally, novel aspects of adipose tissue biology and their involvement in the ageing process are discussed. PMID:28432755

Cognitive dysfunction and depression in adult kidney transplant recipients: baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT)

USDA-ARS?s Scientific Manuscript database

Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment and depression all are common in individuals with kidney disease, including kidney transplant recipient. Accordingly, we assessed the prevalenc...

Association Between Periodontal Disease and Erectile Dysfunction: A Systematic Review.

PubMed

Kellesarian, Sergio Varela; Kellesarian, Tammy Varela; Ros Malignaggi, Vanessa; Al-Askar, Mansour; Ghanem, Alexis; Malmstrom, Hans; Javed, Fawad

2018-03-01

A limited number of studies have reported an association between erectile dysfunction (ED) and chronic periodontitis (CP). The aim of the present study is to assess the association between CP and ED through a systematic review of published literature. To address the focused question, "Is there a relationship between ED and CP?" indexed databases were searched till December 2015 using various key words "erectile dysfunction," "periodontal disease," "periodontitis," "dental infection," and "impotence." Letters to the editor, commentaries, historic reviews, and experimental studies were excluded. The pattern of the present systematic review was customized to primarily summarize the pertinent data. Nine studies were included. Seven studies had a cross-sectional design and two studies were randomized control trials. The number of study participants ranged between 53 and 513,258 individuals with age ranging between 20 years and 85 years (median age ranging between 34.9 ± 4.9 years and 50.9 ± 16.6 years). In all studies, a positive relationship between CP and ED was reported. In four studies, odds ratio were reported, ranging between 1.53 and 3.35. From the literature reviewed, there seems to be a positive association between ED and CP; however, further well-designed controlled clinical trials are needed in this regard. It is emphasized that physicians should refer patients with ED to oral health care providers for a comprehensive oral evaluation and treatment.

Risk stratification and prognostic performance of the predisposition, infection, response, and organ dysfunction (PIRO) scoring system in septic patients in the emergency department: a cohort study.

PubMed

Chen, Yun-Xia; Li, Chun-Sheng

2014-04-16

The predisposition, infection, response and organ dysfunction (PIRO) staging system was designed as a stratification tool to deal with the inherent heterogeneity of septic patients. The present study was conducted to assess the performance of PIRO in predicting multiple organ dysfunction (MOD), intensive care unit (ICU) admission, and 28-day mortality in septic patients in the emergency department (ED), and to compare this scoring system with the Mortality in Emergency Department Sepsis (MEDS) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores. Consecutive septic patients (n = 680) admitted to the ED of Beijing Chao-Yang Hospital were enrolled. PIRO, MEDS, and APACHE II scores were calculated for each patient on ED arrival. Organ function was reassessed within 3 days of enrollment. All patients were followed up for 28 days. Outcome criteria were the development of MOD within 3 days, ICU admission or death within 28 days after enrollment. The predictive ability of the four components of PIRO was analyzed separately. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess the prognostic and risk stratification value of the scoring systems. Organ dysfunction independently predicted ICU admission, MOD, and 28-day mortality, with areas under the ROC curve (AUC) of 0.888, 0.851, and 0.816, respectively. The predictive value of predisposition, infection, and response was weaker than that of organ dysfunction. A negative correlation was found between the response component and MOD, as well as mortality. PIRO, MEDS, and APACHE II scores significantly differed between patients who did and did not meet the outcome criteria (P < 0.001). PIRO and APACHE II independently predicted ICU admission and MOD, but MEDS did not. All three systems were independent predictors of 28-day mortality with similar AUC values. The AUC of PIRO was 0.889 for ICU admission, 0.817 for MOD, and 0.744 for 28-day mortality. The AUCs of PIRO were significantly greater than those of APACHE II and MEDS (P < 0.05) in predicting ICU admission and MOD. The study indicates that PIRO is helpful for risk stratification and prognostic determinations in septic patients in the ED.

Metabolic syndrome and cardiovascular disease: challenges and opportunities.

PubMed

Cooper-DeHoff, Rhonda M; Pepine, Carl J

2007-12-01

Metabolic syndrome (MetS) has been defined in different ways. However, key components common to most definitions are a constellation of risk factors including abdominal adiposity, impaired fasting glucose, hypertension, and dyslipidemia. A major mediator of MetS appears to be insulin resistance, which relates to the development of the vascular and metabolic dysfunctions that precede overt cardiovascular disease and type 2 diabetes. Evidence suggests that the mechanisms underlying the elevated cardiovascular risk associated with MetS begin with subclinical organ damage. Therapy for MetS targets individual components of the syndrome and includes lifestyle interventions, lipid-modifying therapy, and antihypertensive agents, particularly those that inhibit the renin-angiotensin system. Results of trials of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have demonstrated reductions in new-onset diabetes and cardiovascular events in a wide range of patients. Clinical trials to investigate further the role of these drugs in the primary prevention of type 2 diabetes in patients with MetS are currently under way. The purpose of this paper is to review the MetS from the perspective of the cardiology workforce with the hope that a better understanding of the links between MetS and cardiovascular disease could lead to improved management of persons at risk.

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

PubMed Central

Dumnicka, Paulina; Maduzia, Dawid; Ceranowicz, Piotr; Olszanecki, Rafał; Drożdż, Ryszard; Kuśnierz-Cabala, Beata

2017-01-01

Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients. PMID:28208708

Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-for-profit organizations: 2000-2005.

PubMed

Ridker, Paul M; Torres, Jose

2006-05-17

In surveys based on data available prior to 2000, clinical trials funded by for-profit organizations appeared more likely to report positive findings than those funded by not-for-profit organizations. Whether this situation has changed over the past 5 years or whether similar effects are present among jointly funded trials is unknown. To determine in contemporary randomized cardiovascular trials the association between funding source and the likelihood of reporting positive findings. We reviewed 324 consecutive superiority trials of cardiovascular medicine published between January 1, 2000, and July 30, 2005, in JAMA, The Lancet, and the New England Journal of Medicine. The proportion of trials favoring newer treatments over the standard of care was evaluated by funding source. Of the 324 superiority trials, 21 cited no funding source. Of the 104 trials funded solely by not-for-profit organizations, 51 (49%) reported evidence significantly favoring newer treatments over the standard of care, whereas 53 (51%) did not (P = .80). By contrast, 92 (67.2%) of 137 trials funded solely by for-profit organizations favored newer treatments over standard of care (P<.001). Among 62 jointly funded trials, 35 (56.5%), an intermediate proportion, favored newer treatments. For 205 randomized trials evaluating drugs, the proportions favoring newer treatments were 39.5%, not-for-profit; 54.4%, jointly funded; and 65.5%, for-profit trials (P for trend across groups = .002). For the 39 randomized trials evaluating cardiovascular devices, the proportions favoring newer treatments were 50.0%, not-for-profit; 69.2%, jointly funded; and 82.4%, for-profit trials (P for trend across groups = .07). Regardless of funding source, trials using surrogate end points, such as quantitative angiography, intravascular ultrasound, plasma biomarkers, and functional measures were more likely to report positive findings (67%) than trials using clinical end points (54.1%; P = .02). Recent cardiovascular trials funded by for-profit organizations are more likely to report positive findings than trials funded by not-for-profit organizations, as are trials using surrogate rather than clinical end points. Trials jointly funded by not-for-profit and for-profit organizations appear to report positive findings at a rate approximately midway between rates observed in trials supported solely by one or the other of these entities.

Targeting Treatments to Improve Cognitive Function in Mood Disorder: Suggestions From Trials Using Erythropoietin.

PubMed

Miskowiak, Kamilla Woznica; Rush, A John; Gerds, Thomas A; Vinberg, Maj; Kessing, Lars V

2016-12-01

There is no established efficacious treatment for cognitive dysfunction in unipolar and bipolar disorder. This may be partially due to lack of consensus regarding the need to screen for cognitive impairment in cognition trials or which screening criteria to use. We have demonstrated in 2 randomized placebo-controlled trials that 8 weeks of erythropoietin (EPO) treatment has beneficial effects on verbal memory across unipolar and bipolar disorder, with 58% of EPO-treated patients displaying a clinically relevant memory improvement as compared to 15% of those treated with placebo. We reassessed the data from our 2 EPO trials conducted between September 2009 and October 2012 to determine whether objective performance-based memory impairment or subjective self-rated cognitive impairment at baseline was related to the effect of EPO on cognitive function as assessed by Rey Auditory Verbal Learning Test (RAVLT) total recall with multiple logistic regression adjusted for diagnosis, age, gender, symptom severity, and education levels. We included 79 patients with an ICD-10 diagnosis of unipolar or bipolar disorder, of whom 39 received EPO and 40 received placebo (saline). For EPO-treated patients with objective memory dysfunction at baseline (n = 16) (defined as RAVLT total recall ≤ 43), the odds of a clinically relevant memory improvement were increased by a factor of 290.6 (95% CI, 2.7-31,316.4; P = .02) compared to patients with no baseline impairment (n = 23). Subjective cognitive complaints (measured with the Cognitive and Physical Functioning Questionnaire) and longer illness duration were associated with small increases in patients' chances of treatment efficacy on memory (53% and 16% increase, respectively; P ≤ .04). Diagnosis, gender, age, baseline depression severity, and number of mood episodes did not significantly change the chances of EPO treatment success (P ≥ .06). In the placebo-treated group, the odds of memory improvement were not significantly different for patients with or without objectively defined memory dysfunction (P ≥ .59) or subjective complaints at baseline (P ≥ .06). Baseline objectively assessed memory impairments and-to a lesser degree-subjective cognitive complaints increased the chances of treatment efficacy on cognition in unipolar and bipolar disorder. ClinicalTrials.gov identifier: NCT00916552. © Copyright 2016 Physicians Postgraduate Press, Inc.

Pelvic Floor Physical Therapy and Women's Health Promotion.

PubMed

Lawson, Samantha; Sacks, Ashley

2018-05-19

Pelvic floor dysfunction is defined as abnormal function of the pelvic floor and includes conditions that can have significant adverse impacts on a woman's quality of life, including urinary incontinence (stress, urge, and mixed), fecal incontinence, pelvic organ prolapse, sexual dysfunction, diastasis recti abdominis, pelvic girdle pain, and chronic pain syndromes. Women's health care providers can screen for, identify, and treat pelvic floor dysfunction. This article examines the case of a woman with multiple pelvic-floor-related problems and presents the evidence for the use of pelvic floor physical therapy (PFPT) for pregnancy-related pelvic floor dysfunction. PFPT is an evidence-based, low-risk, and minimally invasive intervention, and women's health care providers can counsel women about the role that PFPT may play in the prevention, treatment, and/or management of pelvic floor dysfunction. © 2018 by the American College of Nurse-Midwives.

Recurrent venous thromboembolism in patients with pulmonary embolism and right ventricular dysfunction: a post-hoc analysis of the Hokusai-VTE study.

PubMed

Brekelmans, Marjolein P A; Ageno, Walter; Beenen, Ludo F; Brenner, Benjamin; Buller, Harry R; Chen, Cathy Z; Cohen, Alexander T; Grosso, Michael A; Meyer, Guy; Raskob, Gary; Segers, Annelise; Vanassche, Thomas; Verhamme, Peter; Wells, Philip S; Zhang, George; Weitz, Jeffrey I

2016-09-01

In patients with pulmonary embolism, right ventricular dysfunction is associated with early mortality. The Hokusai-VTE study used N-terminal pro-brain natriuretic peptide (NT-proBNP) and right to left ventricular diameter ratio on CT as indicators of right ventricular dysfunction and reported that recurrent venous thromboembolism rates were lower with edoxaban than warfarin. The aim of the current study was to further explore the significance of right ventricular dysfunction and investigate potential explanations for the superiority of edoxaban-ie, differences in baseline clinical characteristics, duration of initial heparin treatment, bleeding rates, or quality of warfarin treatment. The Hokusai-VTE trial was a randomised, double-blind, event-driven non-inferiority trial in patients from centres in 37 countries that compared edoxaban with warfarin in the treatment of acute venous thromboembolism. Patients received treatment for at least 3 months and up to a maximum of 12 months. Patients were followed up for 12 months. Outcome data at 12 months was collected for all patients irrespective of treatment duration. This prespecified subgroup analysis focuses on the included patients with pulmonary embolism. The primary efficacy outcome was the incidence of adjudicated symptomatic recurrent venous thromboembolism defined as a composite of deep vein thrombosis or non-fatal or fatal pulmonary embolism at 12 months. Recurrence rates with edoxaban and warfarin were compared in patients with and without right ventricular dysfunction. In those with NT-proBNP concentrations of 500 pg/mL or higher, we compared baseline characteristics, duration of heparin treatment, and bleeding leading to study drug discontinuation in the edoxaban and warfarin groups. We also assessed quality of warfarin treatment. All analyses were done with the modified intention-to-treat population. The Hokusai-VTE trial is registered with ClinicalTrials.gov, number NCT00986154. Between Jan 28, 2010, and Oct 5, 2012, 8292 patients were enrolled from 439 centres, of whom 8240 received at least one dose of study drug. 3319 patients had pulmonary embolism. NT-proBNP was 500 pg/mL or higher in 465 (30%) of 1565 patients given edoxaban and in 507 (32%) of 1599 given warfarin. Recurrent venous thromboembolism occurred in 14 (3%) of 465 patients in the edoxaban group and 30 (6%) of 507 in the warfarin group (hazard ratio [HR] 0·50, 95% CI 0·26-0·94; p=0·033). The right to left ventricular diameter ratio was 0·9 or higher in 414 (44%) of 937 patients in the edoxaban group and 427 (45%) of 946 in the warfarin group. Recurrent venous thromboembolism occurred in 11 (3%) of 414 and 20 (5%) of 427 patients in the edoxaban and warfarin groups (HR 0·57, 95% CI 0·27-1·17; p=0·13). Baseline characteristics, duration of heparin treatment, and rates of bleeding leading to study drug discontinuation were similar in the edoxaban and warfarin groups and the quality of warfarin management was adequate for patients with NT-proBNP concentrations of 500 pg/mL or higher. Findings from our analysis suggest that edoxaban is more effective than warfarin in the treatment and prevention of recurrent venous thromboembolism in patients with pulmonary embolism and evidence of right ventricular dysfunction. Daiichi Sankyo. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Motion-Sensing Game-Based Therapy to Foster the Learning of Children with Sensory Integration Dysfunction

ERIC Educational Resources Information Center

Chuang, Tsung-Yen; Kuo, Ming-Shiou

2016-01-01

Children with Sensory Integration Dysfunction (SID, also known as Sensory Processing Disorder, SPD) are also learners with disabilities with regard to responding adequately to the demands made by a learning environment. With problems of organizing and processing the sensation information coming from body modalities, children with SID (CwSID)…

New diagnostic and therapeutic possibilities for diastolic heart failure.

PubMed

Jeong, Euy-Myoung; Dudley, Samuel C

2014-02-03

Despite the fact that up to half of all heart failure occurs in patients without evidence of systolic cardiac dysfunction, there are no universally accepted diagnostic markers and no approved therapies for heart failure with preserved ejection fraction (HFpEF). HFpEF, otherwise known as diastolic heart failure, has nearly the same grim prognosis as systolic heart failure, and diastolic heart failure is increasing in incidence and prevalence. Major trials have shown that many of the treatments that are salutary in systolic heart failure have no beneficial effects in diastolic heart failure, suggesting different underlying mechanisms for these two disorders. Even criteria for diagnosis of HFpEF are still debated, and there is still no gold standard marker to detect diastolic dysfunction. Here, we will review some promising new insights into the pathogenesis of diastolic dysfunction that may lead to new diagnostic and therapeutic tools.

A novel approach to mesh revision after sacrocolpopexy.

PubMed

Dawson, Melissa L; Rebecca, Rinko; Shah, Nima M; Whitmore, Kristene E

2016-01-01

Pelvic organ prolapse (POP) is the herniation of pelvic organs to or beyond the vaginal walls. POP affects 50% of parous women; of those women, 11% will need surgery based on bothersome symptoms. Transvaginal mesh has been used for vaginal augmentation since the 1990s. Complications from mesh use are now more prominent, and include chronic pelvic pain, dyspareunia, vaginal mesh erosion, and urinary and defecatory dysfunction. Presently, there is no consensus regarding treatment of these complications. Reported herein are two cases of women with defecatory dysfunction and pain after sacrocolpopexy who underwent mesh revision procedures performed with both urogynecologic and colorectal surgery.

The use of monoamine pharmacological agents in the treatment of sexual dysfunction: evidence in the literature.

PubMed

Moll, Jennifer L; Brown, Candace S

2011-04-01

The monoamine neurotransmitters serotonin, dopamine, and norepinephrine play an important role in many medical and psychological conditions, including sexual responsiveness and behavior. Pharmacological agents that modulate monoamines may help alleviate sexual dysfunction. To provide an overview of pharmacological agents that modulate monoamines and their use in the treatment of sexual dysfunction. EMBASE and PubMed search for articles published between 1950 and 2010 using key words "sexual dysfunction,"monoamines,"monoaminergic receptors," and "generic names for pharmacological agents." To assess the literature evaluating the efficacy of monoamine pharmacologic agents used in the treatment of sexual dysfunction. The literature primarily cites the use of monoaminergic agents to treat sexual side effects from serotonergic reuptake inhibitors (SSRIs), with bupropion, buspirone and ropinirole providing the most convincing evidence. Controlled trials have shown that bupropion improves overall sexual dysfunction, but not frequency of sexual activity in depressed and nondepressed patients. Nefazodone and apomorphine have been used to treat sexual dysfunction, but their use is limited by significant side effect and safety profiles. New research on pharmacologic agents with subtype selectivity at dopaminergic and serotonergic receptors and those that possess dual mechanisms of action are being investigated. There has been tremendous progress over the past 50 years in understanding the role of monoamines in sexual function and the effect of pharmacologic agents which stimulate or antagonize monoaminergic receptors on sexual dysfunction. Nevertheless, large, double-blind, placebo-controlled studies evaluating the efficacy of currently available agents in populations without comorbid disorders are limited, preventing adequate interpretation of data. Continued research on sexual function and specific receptor subtypes will result in the development of more selective pharmacologic agents with the goal of increasing efficacy without the dose-limiting side effects of nonselective agents. © 2011 International Society for Sexual Medicine.

Co-Occurrence of Developmental Disorders: The Case of Developmental Dyscalculia

ERIC Educational Resources Information Center

Rubinsten, Orly

2009-01-01

Five to seven percent of children experience severe difficulties in learning mathematics and/or reading. Current trials that are focused on identifying biological markers suggest that these learning disabilities, known as Developmental Dyscalculia (DD) and Dyslexia (for reading), are due to underlying brain dysfunctions. One ongoing controversy…

Treatment Outcome and Quality of Life in Patients With Pediatric Extra-Cranial Germ Cell Tumors Previously Treated on Clinical Trial CCLG-GC-1979-01 or CCLG-GC-1989-01

ClinicalTrials.gov

2013-08-09

Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Gastrointestinal Complications; Infertility; Long-term Effects Secondary to Cancer Therapy in Children; Neurotoxicity; Ovarian Cancer; Pulmonary Complications; Sexual Dysfunction; Urinary Complications

Sexual dysfunction and neuroendocrine correlates of posttraumatic stress disorder in combat veterans: Preliminary findings.

PubMed

Lehrner, Amy; Flory, Janine D; Bierer, Linda M; Makotkine, Iouri; Marmar, Charles R; Yehuda, Rachel

2016-01-01

Sexual dysfunction is not a symptom of PTSD but is a common clinical complaint in trauma survivors with this disorder. In that there are biological parallels in the neuroendocrine processes underlying both PTSD and sexual behavior, we conducted an exploratory investigation of the relationship of PTSD and related neuroendocrine indicators with sexual dysfunction in armed service veterans. Major Depressive Disorder, highly comorbid with PTSD and sexual dysfunction, was also assessed. In veterans with PTSD, sexual problems were associated with plasma DHEA and cortisol, urinary catecholamines, and glucocorticoid sensitivity, even when controlling for the effects of comorbid depression. In a subsample analysis, testosterone levels did not distinguish PTSD or sexual dysfunction, suggesting that sexual problems reported by veterans in this sample were not the result of organic disorder. PTSD did predict higher dihydrotestosterone (DHT) levels, which were associated with sexual problems. More detailed assessment of sexual dysfunction in biologically informed studies of PTSD is warranted to clarify the relationships of PTSD symptomatology and related neurobiology with sexual dysfunction. Published by Elsevier Ltd.

Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction

PubMed Central

de Matos, Ana Cristina Carvalho; Requião-Moura, Lúcio Roberto; Clarizia, Gabriela; Durão, Marcelino de Souza; Tonato, Eduardo José; Chinen, Rogério; de Arruda, Érika Ferraz; Filiponi, Thiago Corsi; Pires, Luciana Mello de Mello Barros; Bertocchi, Ana Paula Fernandes; Pacheco-Silva, Alvaro

2015-01-01

ABSTRACT Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction. PMID:26154553

The Case for Adjunctive Monoclonal Antibody Immunotherapy in Schizophrenia.

PubMed

Miller, Brian J; Buckley, Peter F

2016-06-01

This article presents the case in favor of clinical trials of adjunctive monoclonal antibody immunotherapy in schizophrenia. Evidence for prenatal and premorbid immune risk factors for the development of schizophrenia in the offspring is highlighted. Then key evidence for immune dysfunction in patients with schizophrenia is considered. Next, previous trials of adjunctive anti-inflammatory or other immunotherapy in schizophrenia are discussed. Then evidence for psychosis as a side effect of immunotherapy for other disorders is discussed. Also presented is preliminary evidence for adjunctive monoclonal antibody immunotherapy in psychiatric disorders. Finally, important considerations in the design and implementation of clinical trials of adjunctive monoclonal antibody immunotherapy in schizophrenia are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Facing death alone or together? Investigating the interdependence of death anxiety, dysfunctional attitudes and quality of life in patient-caregiver dyads confronting lung cancer.

PubMed

Lau, Bobo Hi-Po; Wong, Daniel F K; Fung, Y L; Zhou, Jillian; Chan, Cecilia L W; Chow, Amy Y M

2018-05-21

Based on the cognitive theory, anxiety arising from the awareness of death and dying may activate dysfunctional attitudes, which may then reduce quality of life. This study examined the interdependence and the mediating role of dysfunctional attitudes on the relationship between death anxiety and quality of life among patients with lung cancer and their caregivers. From March 2016 to April 2017, 173 pairs of patients and their caregivers enrolled in a randomized controlled trial of psychosocial support. Using the baseline data, actor-partner interdependence modelling was used to analyze the relationships among death anxiety, dysfunctional attitudes and quality of life. In patients, death anxiety was related to dependency (β=.51) and self-control (β=-.37); achievement (β=-.21) and self-control (β=.34) were related to quality of life. Among caregivers, death anxiety was related to all three dysfunctional attitudes of their own (βs=.23 to.32); dependency (β=-.22) was associated with quality of life. Caregiver quality of life were also associated with patient self-control (β=.22) and achievement (β=-.18). Patient self-control mediated the links between patient death anxiety with both patient and caregiver quality of life. The relationship between death anxiety and quality of life was mediated by dependency in caregivers. Death anxiety influences dysfunctional attitudes and quality of life of both patients and caregivers. Our results support the relevance of dysfunctional attitudes in understanding the impact of death anxiety and underscore the need for parallel psychosocial interventions. This article is protected by copyright. All rights reserved.

Urological complications of uterine leiomyoma: a review of literature.

PubMed

Dagur, Gautam; Suh, Yiji; Warren, Kelly; Singh, Navjot; Fitzgerald, John; Khan, Sardar A

2016-06-01

Uterine leiomyomas are common gynecologic tumor in reproductive-aged women, by age 50, diagnosis shared by urologist, gynecologists and radiologists. The goal of this article is to review the current literature, study the impact of leiomyoma on female lower urinary tract, examine the cause female sexual dysfunction and provide a comprehensive review of current diagnostic, imaging studies, and current treatment of leiomyoma. Clinical leiomyoma studies published from 1956 through 2015 were identified using the PubMed search engines and the key words leiomyoma, fibroid in the current literature. Impact of leiomyoma on the lower urinary tract including female sexual dysfunction was reviewed with terms of "urinary retention", "bladder", "urethra", "dyspareunia", "incontinence", "incomplete bladder emptying", "female sexual dysfunction", and "lower urinary tract" to study the urological and sexual effects of leiomyoma. Literature related to leiomyoma was reviewed from 1965 to present. Women with uterine leiomyomata complained of pelvic pain, menstrual irregularities, infertility, lower urinary tract symptoms and sexual dysfunction. Leiomyoma is a common tumor of the uterus that often clinically impacts on the lower urinary tract and results in urological and sexual symptoms. Leiomyoma can compress and grow into and become adherent to the bladder and surrounding pelvic organs or metastasize into peritoneal organs. Leiomyoma can enlarge and compress the urinary bladder, urethra, and lower end of the ureters. Leiomyoma can cause embarrassing sexual dysfunction in females. Current literature of non-surgical and surgical therapy of leiomyoma is described.

Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients.

PubMed

Bruder, Eric A; Ball, Ian M; Ridi, Stacy; Pickett, William; Hohl, Corinne

2015-01-08

The use of etomidate for emergency airway interventions in critically ill patients is very common. In one large registry trial, etomidate was the most commonly used agent for this indication. Etomidate is known to suppress adrenal gland function, but it remains unclear whether or not this adrenal gland dysfunction affects mortality. The primary objective was to assess, in populations of critically ill patients, whether a single induction dose of etomidate for emergency airway intervention affects mortality.The secondary objectives were to address, in populations of critically ill patients, whether a single induction dose of etomidate for emergency airway intervention affects adrenal gland function, organ dysfunction, or health services utilization (as measured by intensive care unit (ICU) length of stay (LOS), duration of mechanical ventilation, or vasopressor requirements).We repeated analyses within subgroups defined by the aetiologies of critical illness, timing of adrenal gland function measurement, and the type of comparator drug used. We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; CINAHL; EMBASE; LILACS; International Pharmaceutical Abstracts; Web of Science; the Database of Abstracts of Reviews of Effects (DARE); and ISI BIOSIS Citation index(SM) on 8 February 2013. We reran the searches in August 2014. We will deal with any studies of interest when we update the review.We also searched the Scopus database of dissertations and conference proceedings and the US Food and Drug Administration Database. We handsearched major emergency medicine, critical care, and anaesthesiology journals.We handsearched the conference proceedings of major emergency medicine, anaesthesia, and critical care conferences from 1990 to current, and performed a grey literature search of the following: Current Controlled Trials; National Health Service - The National Research Register; ClinicalTrials.gov; NEAR website. We included randomized controlled trials in patients undergoing emergency endotracheal intubation for critical illness, including but not limited to trauma, stroke, myocardial infarction, arrhythmia, septic shock, hypovolaemic or haemorrhagic shock, and undifferentiated shock states. We included single (bolus) dose etomidate for emergency airway intervention compared to any other rapid-acting intravenous bolus single-dose induction agent. Refinement of our initial search results by title review, and then by abstract review was carried out by three review authors. Full-text review of potential studies was based on their adherence to our inclusion and exclusion criteria. This was decided by three independent review authors. We reported the decisions regarding inclusion and exclusion in accordance with the PRISMA statement.Electronic database searching yielded 1635 potential titles, and our grey literature search yielded an additional 31 potential titles. Duplicate titles were filtered leaving 1395 titles which underwent review of their titles and abstracts by three review authors. Sixty seven titles were judged to be relevant to our review, however only eight met our inclusion criteria and seven were included in our analysis. We included eight studies in the review and seven in the meta-analysis. Of those seven studies, only two were judged to be at low risk of bias. Overall, no strong evidence exists that etomidate increases mortality in critically ill patients when compared to other bolus dose induction agents (odds ratio (OR) 1.17; 95% confidence interval (CI) 0.86 to 1.60, 6 studies, 772 participants, moderate quality evidence). Due to a large number of participants lost to follow-up, we performed a post hoc sensitivity analysis. This gave a similar result (OR 1.15; 95% CI 0.86 to 1.53). There was evidence that the use of etomidate in critically ill patients was associated with a positive adrenocorticotropic hormone (ACTH) stimulation test, and this difference was more pronounced at between 4 to 6 hours (OR 19.98; 95% CI 3.95 to 101.11) than after 12 hours (OR 2.37; 95% CI 1.61 to 3.47) post-dosing. Etomidate's use in critically ill patients was associated with a small increase in SOFA score, indicating a higher risk of multisystem organ failure (mean difference (MD) 0.70; 95% CI 0.01 to 1.39, 2 studies, 591 participants, high quality evidence), but this difference was not clinically meaningful. Etomidate use did not have an effect on ICU LOS (MD 1.70 days; 95% CI -2.00 to 5.40, 4 studies, 621 participants, moderate quality evidence), hospital LOS (MD 2.41 days; 95% CI -7.08 to 11.91, 3 studies, 152 participants, moderate quality evidence), duration of mechanical ventilation (MD 2.14 days; 95% CI -1.67 to 5.95, 3 studies, 621 participants, moderate quality evidence), or duration of vasopressor use (MD 1.00 day; 95% CI -0.53 to 2.53, 1 study, 469 participants). Although we have not found conclusive evidence that etomidate increases mortality or healthcare resource utilization in critically ill patients, it does seem to increase the risk of adrenal gland dysfunction and multi-organ system dysfunction by a small amount. The clinical significance of this finding is unknown. This evidence is judged to be of moderate quality, owing mainly to significant attrition bias in some of the smaller studies, and new research may influence the outcomes of our review. The applicability of these data may be limited by the fact that 42% of the patients in our review were intubated for "being comatose", a population less likely to benefit from the haemodynamic stability inherent in etomidate use, and less at risk from its potential negative downstream effects of adrenal suppression.

High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial.

PubMed

Larsen, Fin Stolze; Schmidt, Lars Ebbe; Bernsmeier, Christine; Rasmussen, Allan; Isoniemi, Helena; Patel, Vishal C; Triantafyllou, Evangelos; Bernal, William; Auzinger, Georg; Shawcross, Debbie; Eefsen, Martin; Bjerring, Peter Nissen; Clemmesen, Jens Otto; Hockerstedt, Krister; Frederiksen, Hans-Jørgen; Hansen, Bent Adel; Antoniades, Charalambos G; Wendon, Julia

2016-01-01

Acute liver failure (ALF) often results in cardiovascular instability, renal failure, brain oedema and death either due to irreversible shock, cerebral herniation or development of multiple organ failure. High-volume plasma exchange (HVP), defined as exchange of 8-12 or 15% of ideal body weight with fresh frozen plasma in case series improves systemic, cerebral and splanchnic parameters. In this prospective, randomised, controlled, multicentre trial we randomly assigned 182 patients with ALF to receive either standard medical therapy (SMT; 90 patients) or SMT plus HVP for three days (92 patients). The baseline characteristics of the groups were similar. The primary endpoint was liver transplantation-free survival during hospital stay. Secondary-endpoints included survival after liver transplantation with or without HVP with intention-to-treat analysis. A proof-of-principle study evaluating the effect of HVP on the immune cell function was also undertaken. For the entire patient population, overall hospital survival was 58.7% for patients treated with HVP vs. 47.8% for the control group (hazard ratio (HR), with stratification for liver transplantation: 0.56; 95% confidence interval (CI), 0.36-0.86; p=0.0083). HVP prior to transplantation did not improve survival compared with patients who received SMT alone (CI 0.37 to 3.98; p=0.75). The incidence of severe adverse events was similar in the two groups. Systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores fell in the treated group compared to control group, over the study period (p<0.001). Treatment with HVP improves outcome in patients with ALF by increasing liver transplant-free survival. This is attributable to attenuation of innate immune activation and amelioration of multi-organ dysfunction. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A case of erectile dysfunction and risk factors for coronary artery disease.

PubMed

Kloner, R A

2005-12-01

The hypothetical case of a man with erectile dysfunction and multiple cardiovascular risk factors is presented to illustrate the use of the second Princeton Consensus Conference Guidelines. Methods to optimize efficacy of the phosphodiesterase inhibitors are described. The overall cardiovascular safety of the phosphodiesterase inhibitors and their interaction with organic nitrates and alpha blockers are discussed.

Interactions between lower urinary tract symptoms and cardiovascular risk factors determine distinct patterns of erectile dysfunction: a latent class analysis.

PubMed

Barbosa, João A B A; Muracca, Eduardo; Nakano, Élcio; Assalin, Adriana R; Cordeiro, Paulo; Paranhos, Mario; Cury, José; Srougi, Miguel; Antunes, Alberto A

2013-12-01

An epidemiological association between lower urinary tract symptoms and erectile dysfunction is well established. However, interactions among multiple risk factors and the role of each in pathological mechanisms are not fully elucidated We enrolled 898 men undergoing prostate cancer screening for evaluation with the International Prostate Symptom Score (I-PSS) and simplified International Index of Erectile Function-5 (IIEF-5) questionnaires. Age, race, hypertension, diabetes, dyslipidemia, metabolic syndrome, cardiovascular disease, serum hormones and anthropometric parameters were also evaluated. Risk factors for erectile dysfunction were identified by logistic regression. The 333 men with at least mild to moderate erectile dysfunction (IIEF 16 or less) were included in a latent class model to identify relationships across erectile dysfunction risk factors. Age, hypertension, diabetes, lower urinary tract symptoms and cardiovascular event were independent predictors of erectile dysfunction (p<0.05). We identified 3 latent classes of patients with erectile dysfunction (R2 entropy=0.82). Latent class 1 had younger men at low cardiovascular risk and a moderate/high prevalence of lower urinary tract symptoms. Latent class 2 had the oldest patients at moderate cardiovascular risk with an increased prevalence of lower urinary tract symptoms. Latent class 3 had men of intermediate age with the highest prevalence of cardiovascular risk factors and lower urinary tract symptoms. Erectile dysfunction severity and lower urinary tract symptoms increased from latent class 1 to 3. Risk factor interactions determined different severities of lower urinary tract symptoms and erectile dysfunction. The effect of lower urinary tract symptoms and cardiovascular risk outweighed that of age. While in the youngest patients lower urinary tract symptoms acted as a single risk factor for erectile dysfunction, the contribution of vascular disease resulted in significantly more severe dysfunction. Applying a risk factor interaction model to prospective trials could reveal distinct classes of drug responses and help define optimal treatment strategies for specific groups. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Clinical trial registration and reporting: a survey of academic organizations in the United States.

PubMed

Mayo-Wilson, Evan; Heyward, James; Keyes, Anthony; Reynolds, Jesse; White, Sarah; Atri, Nidhi; Alexander, G Caleb; Omar, Audrey; Ford, Daniel E

2018-05-02

Many clinical trials conducted by academic organizations are not published, or are not published completely. Following the US Food and Drug Administration Amendments Act of 2007, "The Final Rule" (compliance date April 18, 2017) and a National Institutes of Health policy clarified and expanded trial registration and results reporting requirements. We sought to identify policies, procedures, and resources to support trial registration and reporting at academic organizations. We conducted an online survey from November 21, 2016 to March 1, 2017, before organizations were expected to comply with The Final Rule. We included active Protocol Registration and Results System (PRS) accounts classified by ClinicalTrials.gov as a "University/Organization" in the USA. PRS administrators manage information on ClinicalTrials.gov. We invited one PRS administrator to complete the survey for each organization account, which was the unit of analysis. Eligible organization accounts (N = 783) included 47,701 records (e.g., studies) in August 2016. Participating organizations (366/783; 47%) included 40,351/47,701 (85%) records. Compared with other organizations, Clinical and Translational Science Award (CTSA) holders, cancer centers, and large organizations were more likely to participate. A minority of accounts have a registration (156/366; 43%) or results reporting policy (129/366; 35%). Of those with policies, 15/156 (11%) and 49/156 (35%) reported that trials must be registered before institutional review board approval is granted or before beginning enrollment, respectively. Few organizations use computer software to monitor compliance (68/366; 19%). One organization had penalized an investigator for non-compliance. Among the 287/366 (78%) accounts reporting that they allocate staff to fulfill ClinicalTrials.gov registration and reporting requirements, the median number of full-time equivalent staff is 0.08 (interquartile range = 0.02-0.25). Because of non-response and social desirability, this could be a "best case" scenario. Before the compliance date for The Final Rule, some academic organizations had policies and resources that facilitate clinical trial registration and reporting. Most organizations appear to be unprepared to meet the new requirements. Organizations could enact the following: adopt policies that require trial registration and reporting, allocate resources (e.g., staff, software) to support registration and reporting, and ensure there are consequences for investigators who do not follow standards for clinical research.

Autodigestion: Proteolytic Degradation and Multiple Organ Failure in Shock

PubMed Central

Altshuler, Angelina E.; Kistler, Erik B.; Schmid-Schönbein, Geert W.

2015-01-01

There is currently no effective treatment for multiorgan failure following shock other than alleviation supportive care. A better understanding of the pathogenesis of these sequelae to shock is required. The intestine plays a central role in multiorgan failure. It was previously suggested that bacteria and their toxins are responsible for the organ failure seen in circulatory shock, but clinical trials in septic patients have not confirmed this hypothesis. Instead, we review here evidence that the digestive enzymes, synthesized in the pancreas and discharged into the small intestine as requirement for normal digestion, may play a role in multi-organ failure. These powerful enzymes are non-specific, highly concentrated and fully activated in the lumen of the intestine. During normal digestion they are compartmentalized in the lumen of the intestine by the mucosal epithelial barrier. However, if this barrier becomes permeable, e.g. in an ischemic state, the digestive enzymes escape into the wall of the intestine. They digest tissues in the mucosa and generate small molecular weight cytotoxic fragments such as unbound free fatty acids. Digestive enzymes may also escape into the systemic circulation and activate other degrading proteases. These proteases have the ability to clip the ectodomain of surface receptors and compromise their function; for example cleaving the insulin receptor causing insulin resistance. The combination of digestive enzymes and cytotoxic fragments leaking into the central circulation causes cell and organ dysfunction, and ultimately may lead to complete organ failure and death. We summarize current evidence suggesting that enteral blockade of digestive enzymes inside the lumen of the intestine may serve to reduce acute cell and organ damage and improve survival in experimental shock. PMID:26717111

Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust-induced asthma).

PubMed

Pirie, R S; Collie, D D S; Dixon, P M; McGorum, B C

2003-05-01

Equine heaves is a naturally occurring organic dust-induced asthma characterized by airway neutrophilia, mucus hypersecretion and obstructive lung dysfunction. However, the relative role of different dust components in disease severity remains unclear. This study investigated the relative contribution of inhaled endotoxin and organic dust particulates (mainly mould spores) in inducing heaves in heaves-susceptible horses. Control and heaves-susceptible horses received inhalation challenges with hay dust suspension (HDS) before and after lipopolysaccharide (LPS) depletion. Heaves-susceptible horses also received inhalation challenge with HDS particulates with and without the addition of LPS and were housed in two separate dusty environments during which mould and endotoxin exposure was measured. The airway inflammatory and functional response to each challenge was measured. Depletion of endotoxin from HDS attenuated the airway neutrophilia and abrogated the airway dysfunction induced in heaves horses by inhaled HDS. The airway response was re-established by adding back LPS to the depleted HDS, confirming that the attenuation in airway response was due specifically to endotoxin depletion. Interestingly, the magnitude of alteration in airway response following endotoxin depletion and add-back was greater than that which could be attributed solely to endotoxin per se, indicating that the LPS activity was enhanced by the other dust components. Consistent with this possibility, washed particulates harvested from HDS enhanced the airway response to inhaled LPS in heaves horses. Heaves horses given two different hay/straw challenges had a significantly different severity of airway inflammation and dysfunction, despite airborne dust and endotoxin concentrations in the horses' breathing zones being similar. Although inhaled endotoxin appears not to be the only determinant of disease severity in heaves, it does contribute significantly to the induction of airway inflammation and dysfunction. This contribution is largely via the synergistic action of inhaled endotoxin and organic dust particulates, although other soluble dust components also contribute to a lesser degree.

Long space missions, gene therapy, and the vital role of magnesium: a three-pronged plan for the next 50 years

PubMed Central

Rowe, William J

2010-01-01

Since pharmaceuticals cannot be used in space until liver and kidney dysfunctions are corrected, and with invariable malabsorption, it appears there is no alternative other than to use subcutaneous magnesium (Mg) replacements in the presence of deficiencies and use of gene therapy. I suggest beginning with the correction of as many as four gene deficiencies: atrial natriuretic peptide (ANP), nitric oxide (NO), vascular endothelial growth factor (VEGF), and erythropoietin (EPO), all as well as Mg related to perfusion and angiogenesis. There is no evidence of significant lunar radiation levels in the absence of a solar storm. It could then be determined whether this has resulted in correction of liver and kidney dysfunction. If this persists, serial additions of gene therapy will be required determining the effect of each individual gene trial on organ function. Microgravity and endothelial gaps with leaks trigger reduced plasma volume. Partial correction by use of a plasma volume substitute and development of a delivery device may reduce complexity of gene therapy. Research would be conducted both on Earth and in microgravity, with the development of subcutaneous pharmaceuticals and Mg, and a space walk-reliable subcutaneous silicon device, given that no replenishable subcutaneous device is presently available. A three-pronged approach provides a plan for the next 50 years: A. complete correction of a Mg deficit; B. partial replacement with plasma volume substitutes, and C. multiple gene factor strategy. PMID:21694938

Long space missions, gene therapy, and the vital role of magnesium: a three-pronged plan for the next 50 years.

PubMed

Rowe, William J

2010-01-01

Since pharmaceuticals cannot be used in space until liver and kidney dysfunctions are corrected, and with invariable malabsorption, it appears there is no alternative other than to use subcutaneous magnesium (Mg) replacements in the presence of deficiencies and use of gene therapy. I suggest beginning with the correction of as many as four gene deficiencies: atrial natriuretic peptide (ANP), nitric oxide (NO), vascular endothelial growth factor (VEGF), and erythropoietin (EPO), all as well as Mg related to perfusion and angiogenesis. There is no evidence of significant lunar radiation levels in the absence of a solar storm. It could then be determined whether this has resulted in correction of liver and kidney dysfunction. If this persists, serial additions of gene therapy will be required determining the effect of each individual gene trial on organ function. Microgravity and endothelial gaps with leaks trigger reduced plasma volume. Partial correction by use of a plasma volume substitute and development of a delivery device may reduce complexity of gene therapy. Research would be conducted both on Earth and in microgravity, with the development of subcutaneous pharmaceuticals and Mg, and a space walk-reliable subcutaneous silicon device, given that no replenishable subcutaneous device is presently available. A three-pronged approach provides a plan for the next 50 years: A. complete correction of a Mg deficit; B. partial replacement with plasma volume substitutes, and C. multiple gene factor strategy. 2010 Halvorson et al, publisher and licensee Dove Medical Press Ltd.

A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management

PubMed Central

Matsumoto, Alvin M.

2017-01-01

Abstract Context: Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic–pituitary–testicular axis pathology but have functional hypogonadism that is potentially reversible. Evidence Acquisition: Literature review from 1970 to October 2016. Evidence Synthesis: Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency–like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. Conclusions: There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy. PMID:28359097

Comparing Patients’ Opinions on the Hospital Discharge Process Collected With a Self-Reported Questionnaire Completed Via the Internet or Through a Telephone Survey: An Ancillary Study of the SENTIPAT Randomized Controlled Trial

PubMed Central

Carrat, Fabrice; Hejblum, Gilles

2015-01-01

Background Hospital discharge, a critical stage in the hospital-to-home transition of patient care, is a complex process with potential dysfunctions having an impact on patients’ health on their return home. No study has yet reported the feasibility and usefulness of an information system that would directly collect and transmit, via the Internet, volunteer patients’ opinions on their satisfaction concerning the organization of hospital discharge. Objective Our primary objective was to compare patients’ opinions on the discharge process collected with 2 different methods: self-questionnaire completed on a dedicated website versus a telephone interview. The secondary goal was to estimate patient satisfaction. Methods We created a questionnaire to examine hospital discharge according to 3 dimensions: discharge logistics organization, preplanned posthospital continuity-of-care organization, and patients’ impressions at the time of discharge. A satisfaction score (between 0 and 1) for each of those dimensions and an associated total score were calculated. Taking advantage of the randomized SENTIPAT trial that questioned patients recruited at hospital discharge about the evolution of their health after returning home and randomly assigned them to complete a self-questionnaire directly online or during a telephone interview, we conducted an ancillary study comparing satisfaction with the organization of hospital discharge for these 2 patient groups. The questionnaire was proposed to 1141 patients included in the trial who were hospitalized for ≥2 days, among whom 867 eligible patients had access to the Internet at home and were randomized to the Internet or telephone group. Results Of the 1141 patients included, 755 (66.17%) completed the questionnaire. The response rates for the Internet (39.1%, 168/430) and telephone groups (87.2%, 381/437) differed significantly (P<.001), but their total satisfaction scores did not (P=.08) nor did the satisfaction subscores (P=.58 for discharge logistics organization, P=.12 for preplanned posthospital continuity-of-care organization, and P=.35 for patients’ impressions at the time of discharge). The total satisfaction score (median 0.83, IQR 0.72-0.92) indicated the patients’ high satisfaction. Conclusions The direct transmission of personal health data via the Internet requires patients’ active participation and those planning surveys in the domain explored in this study should anticipate a lower response rate than that issued from a similar survey conducted by telephone interviews. Nevertheless, collecting patients’ opinions on their hospital discharge via the Internet proved operational; study results indicate that conducting such surveys via the Internet yields similar estimates to those obtained via a telephone survey. The results support the establishment of a permanent dedicated website that could also be used to obtain users’ opinions on other aspects of their hospital stay and follow-up. Trial Registration Clinicaltrials.gov NCT01769261; http://clinicaltrials.gov/ct2/show/NCT01769261 (Archived by WebCite at http://www.webcitation.org/6ZDF5bdQb). PMID:26109261

Multiple organ dysfunction syndrome, an unusual complication of heroin intoxication: a case report and review of literature.

PubMed

Feng, Gang; Luo, Qiancheng; Guo, Enwei; Yao, Yulan; Yang, Feng; Zhang, Bingyu; Li, Longxuan

2015-01-01

Multiple organ dysfunction syndrome (MODS) has rarely been described in patients with heroin intoxication. Here, we report a rare case of MODS involving six organs, due to heroin intoxication. The patient was a 32-year-old Chinese man with severe heroin intoxication complicated by acute pulmonary edema and respiratory insufficiency, shock, myocardial damage and cardiac insufficiency, rhabdomyolysis and acute renal insufficiency, acute liver injury and hepatic insufficiency, toxic leukoencephalopathy, and hypoglycemia. He managed to survive and was discharged after 10 weeks of intensive care. The possible pathogenesis and therapeutic measures of MODS induced by heroin intoxication and some suggestions for preventing and treating severe complications of heroin intoxication, based on clinical evidence and the pertinent literature, are discussed in this report.

Effect of Vortioxetine vs. Escitalopram on Sexual Functioning in Adults with Well-Treated Major Depressive Disorder Experiencing SSRI-Induced Sexual Dysfunction.

PubMed

Jacobsen, Paula L; Mahableshwarkar, Atul R; Chen, Yinzhong; Chrones, Lambros; Clayton, Anita H

2015-10-01

Sexual dysfunction is common with serotonergic antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), and does not resolve in most patients. Vortioxetine, an antidepressant with a multimodal mechanism of action, has shown low rates of sexual dysfunction in previous major depressive disorder (MDD) trials. This study compared the effects of vortioxetine and escitalopram on sexual functioning in adults with well-treated MDD experiencing treatment-emergent sexual dysfunction (TESD). Participants treated with, and responding to, citalopram, paroxetine, or sertraline were randomized to switch to either vortioxetine (10/20 mg; n = 225) or escitalopram (10/20 mg; n = 222) for 8 weeks. Sexual function was assessed using the Changes in Sexual Functioning Questionnaire Short Form (CSFQ-14), and antidepressant efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI) scale, and Profile of Mood States brief form (POMS-brief). Safety and tolerability were also assessed. The primary endpoint was change from baseline in the CSFQ-14 total score after 8 weeks of treatment. The MADRS, CGI, and POMS-brief were used to assess antidepressant efficacy. Safety was assessed via adverse events, vital signs, electrocardiograms, laboratory values, weight, and physical examination findings. Vortioxetine showed significantly greater improvements in CSFQ-14 total score (8.8 ± 0.64, mean ± standard error) vs. escitalopram (6.6 ± 0.64; P = 0.013). Benefits vs. escitalopram were significant on four of five dimensions and all three phases of sexual functioning assessed by the CSFQ-14 (P < 0.05). Antidepressant efficacy continued in both groups, with similar, but slight, improvements in MADRS and CGI scores. Vortioxetine and escitalopram had similar clinical efficacy profiles in this study, with safety profiles similar to previous trials. Nausea (n = 9, 4.0%) was the most common treatment-emergent adverse event leading to discontinuation of vortioxetine. Switching antidepressant therapy to vortioxetine may be beneficial for patients experiencing sexual dysfunction during antidepressant therapy with SSRIs. © 2015 International Society for Sexual Medicine.

Fermented Milk Containing Lactobacillus casei Strain Shirota Preserves the Diversity of the Gut Microbiota and Relieves Abdominal Dysfunction in Healthy Medical Students Exposed to Academic Stress.

PubMed

Kato-Kataoka, Akito; Nishida, Kensei; Takada, Mai; Kawai, Mitsuhisa; Kikuchi-Hayakawa, Hiroko; Suda, Kazunori; Ishikawa, Hiroshi; Gondo, Yusuke; Shimizu, Kensuke; Matsuki, Takahiro; Kushiro, Akira; Hoshi, Ryoutaro; Watanabe, Osamu; Igarashi, Tomoki; Miyazaki, Kouji; Kuwano, Yuki; Rokutan, Kazuhito

2016-06-15

Stress-induced abdominal dysfunction is an attractive target for probiotics. To investigate the effects of the probiotic Lactobacillus casei strain Shirota on abdominal dysfunction, a double-blind, placebo-controlled trial was conducted with healthy medical students undertaking an authorized nationwide examination for academic advancement. For 8 weeks, until the day before the examination, 23 and 24 subjects consumed an L. casei strain Shirota-fermented milk and a placebo milk daily, respectively. In addition to assessments of abdominal symptoms, psychophysical state, and salivary stress markers, gene expression changes in peripheral blood leukocytes and composition of the gut microbiota were analyzed using DNA microarray analysis and 16S rRNA gene amplicon sequence analysis, respectively, before and after the intervention. Stress-induced increases in a visual analog scale measuring feelings of stress, the total score of abdominal dysfunction, and the number of genes with changes in expression of more than 2-fold in leukocytes were significantly suppressed in the L. casei strain Shirota group compared with those in the placebo group. A significant increase in salivary cortisol levels before the examination was observed only in the placebo group. The administration of L. casei strain Shirota, but not placebo, significantly reduced gastrointestinal symptoms. Moreover, 16S rRNA gene amplicon sequencing demonstrated that the L. casei strain Shirota group had significantly higher numbers of species, a marker of the alpha-diversity index, in their gut microbiota and a significantly lower percentage of Bacteroidaceae than the placebo group. Our findings indicate that the daily consumption of probiotics, such as L. casei strain Shirota, preserves the diversity of the gut microbiota and may relieve stress-associated responses of abdominal dysfunction in healthy subjects exposed to stressful situations. A novel clinical trial was conducted with healthy medical students under examination stress conditions. It was demonstrated that the daily consumption of lactic acid bacteria provided health benefits to prevent the onset of stress-associated abdominal symptoms and a good change of gut microbiota in healthy medical students. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Association between plantar fascia vascularity and morphology and foot dysfunction in individuals with chronic plantar fasciitis.

PubMed

Chen, Hongying; Ho, Hok-Ming; Ying, Michael; Fu, Siu Ngor

2013-10-01

Single-cohort laboratory-based study. To identify whether plantar fascia vascularity and thickness are associated with foot pain and dysfunction in individuals with chronic plantar fasciitis. Background Altered plantar fascia vascularity and thickening of the fascia have been identified in individuals with chronic plantar fasciitis. Thirty-eight patients with chronic unilateral plantar fasciitis and 21 controls participated in this study. Proximal plantar fascia vascularization and thickness were assessed using ultrasound imaging, and pain and foot dysfunction were quantified with a visual analog scale and the Chinese version of the Foot Function Index, respectively. Paired t tests were used to assess the side-to-side differences in fascia thickness and vascularity index (VI) in the control and patient groups, and an unpaired t test was used to make comparisons with the patient group. Multiple regression analysis was performed to identify whether the VI and fascia thickness were associated with pain and foot dysfunction. There were significantly higher VI (mean ± SD, 2.4% ± 1.4%) and fascia thickness (5.0 ± 1.3 mm) values in the affected feet when compared with the unaffected feet in the patient group (VI, 1.4% ± 0.5%; fascia thickness, 3.3 ± 0.7 mm) and with the dominant side of the controls (VI, 1.6% ± 0.4%; fascia thickness, 2.9 ± 0.6 mm). After accounting for age, gender, body mass index, and duration of symptoms, the VI explained 13% and 33% of the variance in pain scores measured with a visual analog scale and the pain subscale of the Foot Function Index, respectively; the VI and fascia thickness explained 42% of the variance in the Foot Function Index. Individuals with unilateral chronic plantar fasciitis demonstrated significantly greater vascularity and thickened fascia on the affected side compared to the unaffected side and also to healthy controls. Fascia vascularity was associated independently with self-perceived pain, and both fascia vascularity and thickness were associated with foot dysfunction in patients with chronic plantar fasciitis. Public trials registry: Current Controlled Trials, ISRCTN49594569.

Effects of industrially produced trans fat on markers of systemic inflammation: evidence from a randomized trial in women

USDA-ARS?s Scientific Manuscript database

Background: Intake of industrial trans fatty acids (TFA) has been positively associated to systemic markers of low-grade inflammation and endothelial dysfunction in cross-sectional studies, but results from intervention studies are inconclusive. Objective: To examine the effect of a high intake of T...

75 FR 9231 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-01

... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Metabolic Dysfunction Collaborative... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; CAMUS Trial. Date: April 2...

Brief Report: Acamprosate in Fragile X Syndrome

ERIC Educational Resources Information Center

Erickson, Craig A.; Mullett, Jennifer E.; McDougle, Christopher J.

2010-01-01

Glutamatergic dysfunction is implicated in the pathophysiology of fragile X syndrome (FXS). We report on the first trial of acamprosate, a drug with putative mGluR5 antagonism, in three adults with FXS and autism. Medical records describing open-label treatment with acamprosate in 3 patients with FXS and a comorbid diagnosis of autistic disorder…

Complementary feeding with cowpea reduces growth faltering in rural Malawian infants: A blind, randomized controlled clinical trial

USDA-ARS?s Scientific Manuscript database

Growth faltering is common in rural African children and is attributed to inadequate dietary intake and environmental enteric dysfunction (EED). We tested the hypothesis that complementary feeding with cowpea or common bean flour would reduce growth faltering and EED in 6-mo-old rural Malawians com...

The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis.

PubMed

Lowes, Damon A; Thottakam, Bensita M V; Webster, Nigel R; Murphy, Michael P; Galley, Helen F

2008-12-01

Sepsis is characterised by a systemic dysregulated inflammatory response and oxidative stress, often leading to organ failure and death. Development of organ dysfunction associated with sepsis is now accepted to be due at least in part to oxidative damage to mitochondria. MitoQ is an antioxidant selectively targeted to mitochondria that protects mitochondria from oxidative damage and which has been shown to decrease mitochondrial damage in animal models of oxidative stress. We hypothesised that if oxidative damage to mitochondria does play a significant role in sepsis-induced organ failure, then MitoQ should modulate inflammatory responses, reduce mitochondrial oxidative damage, and thereby ameliorate organ damage. To assess this, we investigated the effects of MitoQ in vitro in an endothelial cell model of sepsis and in vivo in a rat model of sepsis. In vitro MitoQ decreased oxidative stress and protected mitochondria from damage as indicated by a lower rate of reactive oxygen species formation (P=0.01) and by maintenance of the mitochondrial membrane potential (P<0.005). MitoQ also suppressed proinflammatory cytokine release from the cells (P<0.05) while the production of the anti-inflammatory cytokine interleukin-10 was increased by MitoQ (P<0.001). In a lipopolysaccharide-peptidoglycan rat model of the organ dysfunction that occurs during sepsis, MitoQ treatment resulted in lower levels of biochemical markers of acute liver and renal dysfunction (P<0.05), and mitochondrial membrane potential was augmented (P<0.01) in most organs. These findings suggest that the use of mitochondria-targeted antioxidants such as MitoQ may be beneficial in sepsis.

Combining neuroendocrine inhibitors in heart failure: reflections on safety and efficacy.

PubMed

Jneid, Hani; Moukarbel, George V; Dawson, Bart; Hajjar, Roger J; Francis, Gary S

2007-12-01

Neuroendocrine activation in heart failure has become the major target of pharmacotherapy for this growing epidemic. Agents targeting the renin-angiotensin-aldosterone and sympathetic nervous systems have shown cardiovascular and survival benefits in clinical trials. Beta-blockers and angiotensin-converting enzyme (ACE) inhibitors remain the mainstream initial therapy. The benefits of aldosterone antagonists have been demonstrated in advanced heart failure (spironolactone) and after myocardial infarction complicated by left ventricular dysfunction and heart failure (eplerenone). Emerging clinical evidence demonstrated that angiotensin receptor blockers may be a reasonable alternative to ACE inhibitors in patients with heart failure (candesartan) and following myocardial infarction complicated by heart failure or left ventricular dysfunction (valsartan). Angiotensin receptor blockers (candesartan) also provided incremental benefits when added to ACE inhibitors in chronic heart failure. Thus, combining neuroendocrine inhibitors in heart failure appears both biologically plausible and evidence-based. However, this approach raised concerns about side effects, such as hypotension, renal insufficiency, hyperkalemia, and others. Close follow-up and implementation of evidence-based medicine (ie, using agents and doses proven beneficial in clinical trials) should therefore be undertaken when combining neuroendocrine inhibitors.

Erectile dysfunction post-radical prostatectomy – a challenge for both patient and physician

PubMed Central

Bratu, O; Oprea, I; Marcu, D; Spinu, D; Niculae, A; Geavlete, B; Mischianu, D

2017-01-01

Post-radical prostatectomy erectile dysfunction (post RP ED) is a major postoperative complication with a great impact on the quality of life of the patients. Until present, no proper algorithm or guideline based on the clinical trials has been established for the management of post RP ED. According to literature, it is better to initiate a penile rehabilitation program as soon as possible after surgery than doing nothing, in order to prevent and limit the postoperative local hypoxygenation and fibrosis. The results of numerous clinical trials regarding the effectiveness of the phosphodiesterase 5 inhibitors therapy on post RP ED have made them the gold standard treatment. Encouraging results have been achieved in studies with vacuum erectile devices, intraurethral suppositories with alprostadil and intracavernosal injections, but due to their side effects, especially in the cases of intracavernosal injections and intraurethral suppositories, their clinical use was limited therefore making them a second line option for the post RP ED treatment. What should not be forgotten is that penile implant prosthesis has proven very effective, numerous studies confirming high rates of satisfaction for both patients and partners. PMID:28255370

A Systematic Review of Randomized Controlled Trials Examining the Effectiveness of Saffron (Crocus sativus L.) on Psychological and Behavioral Outcomes

PubMed Central

Hausenblas, Heather Ann; Heekin, Kacey; Mutchie, Heather Lee; Anton, Stephen

2017-01-01

Introduction Throughout the past three decades, increased scientific attention has been given to examining saffron’s (Crocus sativus L.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression. Saffron has been shown to improve numerous health-related physiological to psychological outcomes. The purpose of this systematic review is to examine and categorize the current state of scientific evidence from randomized controlled trials (RCTs) regarding the efficacy of saffron on psychological and behavioral outcomes. Methods Electronic and non-electronic systematic searches were conducted to identify all relevant human clinical research on saffron. The search strategy was extensive and was designed according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)”. Reference lists of articles that met the inclusion criteria were searched. Only English language studies were reviewed. Results Twelve studies met our inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes with respect to the following health conditions: major depressive disorder (n = 6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n = 4), and weight loss/snacking behaviors (n = 1). The data from these studies support the efficacy of saffron in improving: depressive symptoms, premenstrual symptoms, sexual function, and satiety. Conclusion Findings from initial clinical trials suggest that saffron can improve the symptoms and effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings. PMID:26165367

Improving BPH symptoms and sexual dysfunctions with a saw palmetto preparation? Results from a pilot trial.

PubMed

Suter, Andreas; Saller, Reinhard; Riedi, Eugen; Heinrich, Michael

2013-02-01

In elderly men, benign prostatic hyperplasia (BPH) is a major risk factor for sexual dysfunctions (SDys). Additionally, the standard treatments for BPH symptoms, alpha blockers and 5-alpha-reductase inhibitors, cause SDys themselves. Preparations from saw palmetto berries are an efficacious and well-tolerated symptomatic treatment for mild to moderate BPH and have traditionally been used to treat SDys. We conducted an open multicentric clinical pilot trial to investigate whether the saw palmetto berry preparation Prostasan® influenced BPH symptoms and SDys. Eighty-two patients participated in the 8-week trial, taking one capsule of 320 mg saw palmetto extract daily. At the end of the treatment, the International Prostate Symptom Score was reduced from 14.4 ± 4.7 to 6.9 ± 5.2 (p < 0.0001); SDys measured with the brief Sexual Function Inventory improved from 22.4 ± 7.2 to 31.4 ± 9.2 (p < 0.0001), and the Urolife BPH QoL-9 sex total improved from 137.3 ± 47.9 to 195.0 ± 56.3 (p < 0.0001). Investigators' and patients' assessments confirmed the good efficacy, and treatment was very well tolerated and accepted by the patients. Correlation analyses confirmed the relationship between improved BPH symptoms and reduced SDys. This was the first trial with saw palmetto to show improvement in BPH symptoms and SDys as well. [Corrections made here after initial online publication.] Copyright © 2012 John Wiley & Sons, Ltd.

The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial.

PubMed

Schädler, Dirk; Pausch, Christine; Heise, Daniel; Meier-Hellmann, Andreas; Brederlau, Jörg; Weiler, Norbert; Marx, Gernot; Putensen, Christian; Spies, Claudia; Jörres, Achim; Quintel, Michael; Engel, Christoph; Kellum, John A; Kuhlmann, Martin K

2017-01-01

We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

Investigation of erectile dysfunction.

PubMed

Patel, D V; Halls, J; Patel, U

2012-11-01

Erectile dysfunction (ED) represents a common and debilitating condition with a wide range of organic and non-organic causes. Physical aetiologies can be divided into disorders affecting arterial inflow, the venous occlusion mechanism or the penile structure itself. Various imaging modalities can be utilised to investigate the physical causes of ED, but penile Doppler sonography (PDS) is the most informative technique, indicated in those patients with ED who do not respond to oral pharmacological agents (e.g. phosphodiesterase type 5 inhibitors). This review will examine the anatomical and physiological basis of penile erection, the method for performing PDS and features of specific causes of ED, and will also consider the alternative imaging modalities available.

Review: Pathogenesis of canine atopic dermatitis: skin barrier and host-micro-organism interaction.

PubMed

Santoro, Domenico; Marsella, Rosanna; Pucheu-Haston, Cherie M; Eisenschenk, Melissa N C; Nuttall, Tim; Bizikova, Petra

2015-04-01

Canine atopic dermatitis (AD) is a common, genetically predisposed, inflammatory and pruritic skin disease. The pathogenesis of canine AD is incompletely understood. The aim of this review is to provide an in-depth update on the involvement of skin barrier and host-microbiome interaction in the pathogenesis of canine AD. Online citation databases and abstracts from international meetings were searched for publications related to skin barrier and host-microbiome interaction (e.g. bacteria, yeast, antimicrobial peptides). A total of 126 publications were identified. This review article focuses on epidermal barrier dysfunction and the interaction between cutaneous microbes (bacteria and yeasts) and the host (antimicrobial peptides). Epidemiological updates on the presence of pathogenic organisms and canine AD are also provided. Major advances have been made in the investigation of skin barrier dysfunction in canine AD, although many questions still remain. Skin barrier dysfunction and host-microbiome interactions are emerging as primary alterations in canine AD. Based on this review, it is clear that future studies focused on the development of drugs able to restore the skin barrier and increase the natural defences against pathogenic organisms are needed. © 2015 ESVD and ACVD.

Familial dysautonomia: History, genotype, phenotype and translational research.

PubMed

Norcliffe-Kaufmann, Lucy; Slaugenhaupt, Susan A; Kaufmann, Horacio

2017-05-01

Familial dysautonomia (FD) is a rare neurological disorder caused by a splice mutation in the IKBKAP gene. The mutation arose in the 1500s within the small Jewish founder population in Eastern Europe and became prevalent during the period of rapid population expansion within the Pale of Settlement. The carrier rate is 1:32 in Jews descending from this region. The mutation results in a tissue-specific deficiency in IKAP, a protein involved in the development and survival of neurons. Patients homozygous for the mutations are born with multiple lesions affecting mostly sensory (afferent) fibers, which leads to widespread organ dysfunction and increased mortality. Neurodegenerative features of the disease include progressive optic atrophy and worsening gait ataxia. Here we review the progress made in the last decade to better understand the genotype and phenotype. We also discuss the challenges of conducting controlled clinical trials in this rare medically fragile population. Meanwhile, the search for better treatments as well as a neuroprotective agent is ongoing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of a novel cytokine haemoadsorbtion system on inflammatory response in septic shock after cephalic pancreatectomy – a case report

PubMed Central

Tomescu, Dana; Dima, Simona O.; Tănăsescu, Sabina; Tănase, Cristiana Pistol; Năstase, Anca; Popescu, Mihai

2014-01-01

Severe sepsis and septic shock are associated with an inflammatory cascade that is primarily responsible for multiple organ dysfunction. To date, there are no specific treatments designed to modulate and rebalance inflammatory cytokines levels. We present a case of a 50 years old man with postoperative septic shock after undergoing cephalic pancreatectomy for a pancreatic cystic tumor. The use of a haemoadsorbtion device (CytoSorb®) in combination with continuous veno-venous haemofiltration was associated with a decrease in TNFα, IL-1β and IFNγ and an increase in IL-10 levels measured before and after two consecutive procedures. The effect of CytoSorb® on inflammatory cytokines translated into a more stable haemodynamic profile with a stable cardiac output and normalization of systemic vascular resistance index and decreased vasopressor requirements. Further prospective large clinical trials are required in order to determine the indications for CytoSorb® and to evaluate the overall outcome. PMID:28913446

Effects of a novel cytokine haemoadsorbtion system on inflammatory response in septic shock after cephalic pancreatectomy - a case report.

PubMed

Tomescu, Dana; Dima, Simona O; Tănăsescu, Sabina; Tănase, Cristiana Pistol; Năstase, Anca; Popescu, Mihai

2014-10-01

Severe sepsis and septic shock are associated with an inflammatory cascade that is primarily responsible for multiple organ dysfunction. To date, there are no specific treatments designed to modulate and rebalance inflammatory cytokines levels. We present a case of a 50 years old man with postoperative septic shock after undergoing cephalic pancreatectomy for a pancreatic cystic tumor. The use of a haemoadsorbtion device (CytoSorb ® ) in combination with continuous veno-venous haemofiltration was associated with a decrease in TNFα, IL-1β and IFNγ and an increase in IL-10 levels measured before and after two consecutive procedures. The effect of CytoSorb ® on inflammatory cytokines translated into a more stable haemodynamic profile with a stable cardiac output and normalization of systemic vascular resistance index and decreased vasopressor requirements. Further prospective large clinical trials are required in order to determine the indications for CytoSorb ® and to evaluate the overall outcome.

Data-driven modelling of social forces and collective behaviour in zebrafish.

PubMed

Zienkiewicz, Adam K; Ladu, Fabrizio; Barton, David A W; Porfiri, Maurizio; Bernardo, Mario Di

2018-04-14

Zebrafish are rapidly emerging as a powerful model organism in hypothesis-driven studies targeting a number of functional and dysfunctional processes. Mathematical models of zebrafish behaviour can inform the design of experiments, through the unprecedented ability to perform pilot trials on a computer. At the same time, in-silico experiments could help refining the analysis of real data, by enabling the systematic investigation of key neurobehavioural factors. Here, we establish a data-driven model of zebrafish social interaction. Specifically, we derive a set of interaction rules to capture the primary response mechanisms which have been observed experimentally. Contrary to previous studies, we include dynamic speed regulation in addition to turning responses, which together provide attractive, repulsive and alignment interactions between individuals. The resulting multi-agent model provides a novel, bottom-up framework to describe both the spontaneous motion and individual-level interaction dynamics of zebrafish, inferred directly from experimental observations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hippocampal-prefrontal theta-gamma coupling during performance of a spatial working memory task.

PubMed

Tamura, Makoto; Spellman, Timothy J; Rosen, Andrew M; Gogos, Joseph A; Gordon, Joshua A

2017-12-19

Cross-frequency coupling supports the organization of brain rhythms and is present during a range of cognitive functions. However, little is known about whether and how long-range cross-frequency coupling across distant brain regions subserves working memory. Here we report that theta-slow gamma coupling between the hippocampus and medial prefrontal cortex (mPFC) is augmented in a genetic mouse model of cognitive dysfunction. This increased cross-frequency coupling is observed specifically when the mice successfully perform a spatial working memory task. In wild-type mice, increasing task difficulty by introducing a long delay or by optogenetically interfering with encoding, also increases theta-gamma coupling during correct trials. Finally, epochs of high hippocampal theta-prefrontal slow gamma coupling are associated with increased synchronization of neurons within the mPFC. These findings suggest that enhancement of theta-slow gamma coupling reflects a compensatory mechanism to maintain spatial working memory performance in the setting of increased difficulty.

Understanding the impact of hypoglycemia on the cardiovascular system

PubMed Central

Davis, Ian Charles; Ahmadizadeh, Ida; Randell, Jacqueline; Younk, Lisa; Davis, Stephen N

2017-01-01

Introduction Hypoglycemia occurs commonly in insulin requiring individuals with either Type 1 or Type 2 Diabetes. Areas Covered This article will review recent information on the pro-inflammatory and pro-atherothrombotic effects of hypoglycemia. Additionally, effects of hypoglycemia on arrhythmogenic potential and arterial endothelial dysfunction will be discussed. Effects of hypoglycemia on cardiovascular morbidity and mortality from large clinical studies in Type 1 and Type 2 DM will also be reviewed. Expert Commentary The relative and absolute risk of severe hypoglycemia leading to death and serious adverse events in both cardiovascular and other organ systems has been highlighted following the publication of recent large clinical trials focused on glucose control and outcomes. It would be helpful if future studies could develop broader end points to include minor and moderate hypoglycemia as well as more robust methods for capturing hypoglycemia contemporaneously with adverse events. In addition, perhaps consideration of including hypoglycemia as a primary outcome, may help identify the possible cause and effect of hypoglycemia on cardiovascular morbidity and mortality. PMID:29109754

Acromegaly pathogenesis and treatment

PubMed Central

Melmed, Shlomo

2009-01-01

Dysregulated growth hormone (GH) hypersecretion is usually caused by a GH-secreting pituitary adenoma and leads to acromegaly — a disorder of disproportionate skeletal, tissue, and organ growth. High GH and IGF1 levels lead to comorbidities including arthritis, facial changes, prognathism, and glucose intolerance. If the condition is untreated, enhanced mortality due to cardiovascular, cerebrovascular, and pulmonary dysfunction is associated with a 30% decrease in life span. This Review discusses acromegaly pathogenesis and management options. The latter include surgery, radiation, and use of novel medications. Somatostatin receptor (SSTR) ligands inhibit GH release, control tumor growth, and attenuate peripheral GH action, while GH receptor antagonists block GH action and effectively lower IGF1 levels. Novel peptides, including SSTR ligands, exhibiting polyreceptor subtype affinities and chimeric dopaminergic-somatostatinergic properties are currently in clinical trials. Effective control of GH and IGF1 hypersecretion and ablation or stabilization of the pituitary tumor mass lead to improved comorbidities and lowering of mortality rates for this hormonal disorder. PMID:19884662

Association Between Periodontal Disease and Erectile Dysfunction: A Systematic Review

PubMed Central

Kellesarian, Sergio Varela; Kellesarian, Tammy Varela; Ros Malignaggi, Vanessa; Al-Askar, Mansour; Ghanem, Alexis; Malmstrom, Hans; Javed, Fawad

2016-01-01

A limited number of studies have reported an association between erectile dysfunction (ED) and chronic periodontitis (CP). The aim of the present study is to assess the association between CP and ED through a systematic review of published literature. To address the focused question, “Is there a relationship between ED and CP?” indexed databases were searched till December 2015 using various key words “erectile dysfunction,” “periodontal disease,” “periodontitis,” “dental infection,” and “impotence.” Letters to the editor, commentaries, historic reviews, and experimental studies were excluded. The pattern of the present systematic review was customized to primarily summarize the pertinent data. Nine studies were included. Seven studies had a cross-sectional design and two studies were randomized control trials. The number of study participants ranged between 53 and 513,258 individuals with age ranging between 20 years and 85 years (median age ranging between 34.9 ± 4.9 years and 50.9 ± 16.6 years). In all studies, a positive relationship between CP and ED was reported. In four studies, odds ratio were reported, ranging between 1.53 and 3.35. From the literature reviewed, there seems to be a positive association between ED and CP; however, further well-designed controlled clinical trials are needed in this regard. It is emphasized that physicians should refer patients with ED to oral health care providers for a comprehensive oral evaluation and treatment. PMID:27030114

Eplerenone: a selective aldosterone receptor antagonist for patients with heart failure.

PubMed

Barnes, Brian J; Howard, Patricia A

2005-01-01

To evaluate the pharmacology, pharmacokinetics, safety, and clinical use of eplerenone in heart failure (HF). English-language MEDLINE searches were performed from 1966 to May 2004. Key words included eplerenone, aldosterone receptor antagonist, heart failure, myocardial infarction, left-ventricular dysfunction, and cost-effectiveness. Additional references were identified from bibliographies of selected articles. Human trials evaluating the efficacy, safety, and cost-effectiveness of aldosterone receptor antagonists in HF were evaluated. Eplerenone is the first selective aldosterone receptor antagonist. The drug is indicated to improve the survival of stable patients with left-ventricular systolic dysfunction (ejection fraction <40%) and clinical evidence of HF following acute myocardial infarction. Efficacy and safety in this population have been demonstrated in a large, randomized clinical trial. Eplerenone is associated with severe and sometimes life-threatening hyperkalemia. Patients with reduced renal function and diabetes, as well as those on other drugs that increase potassium levels, are at highest risk. Eplerenone is metabolized by the cytochrome P450 system and may interact with drugs that interfere with this system. A major advantage of eplerenone over the nonselective aldosterone receptor antagonist spironolactone is lack of binding to progesterone and androgen receptors, which is associated with drug-induced gynecomastia, breast pain, and impotence. The addition of eplerenone to traditional HF therapy has been shown to reduce morbidity and mortality in patients who develop left-ventricular dysfunction after acute myocardial infarction. Eplerenone's selectivity reduces sex hormone-related adverse effects. Despite these benefits, the overall cost-effectiveness has yet to be determined.

Sodium-to-Potassium Ratio and Blood Pressure, Hypertension, and Related Factors12

PubMed Central

Perez, Vanessa; Chang, Ellen T.

2014-01-01

The potential cost-effectiveness and feasibility of dietary interventions aimed at reducing hypertension risk are of considerable interest and significance in public health. In particular, the effectiveness of restricted sodium or increased potassium intake on mitigating hypertension risk has been demonstrated in clinical and observational research. The role that modified sodium or potassium intake plays in influencing the renin-angiotensin system, arterial stiffness, and endothelial dysfunction remains of interest in current research. Up to the present date, no known systematic review has examined whether the sodium-to-potassium ratio or either sodium or potassium alone is more strongly associated with blood pressure and related factors, including the renin-angiotensin system, arterial stiffness, the augmentation index, and endothelial dysfunction, in humans. This article presents a systematic review and synthesis of the randomized controlled trials and observational research related to this issue. The main findings show that, among the randomized controlled trials reviewed, the sodium-to-potassium ratio appears to be more strongly associated with blood pressure outcomes than either sodium or potassium alone in hypertensive adult populations. Recent data from the observational studies reviewed provide additional support for the sodium-to-potassium ratio as a superior metric to either sodium or potassium alone in the evaluation of blood pressure outcomes and incident hypertension. It remains unclear whether this is true in normotensive populations and in children and for related outcomes including the renin-angiotensin system, arterial stiffness, the augmentation index, and endothelial dysfunction. Future study in these populations is warranted. PMID:25398734

Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events?

PubMed

Als-Nielsen, Bodil; Chen, Wendong; Gluud, Christian; Kjaergard, Lise L

2003-08-20

Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions. To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events. Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication). Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not. The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events. Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data.

Interplay Between Premature Ejaculation and Erectile Dysfunction: A Systematic Review and Meta-Analysis.

PubMed

Corona, Giovanni; Rastrelli, Giulia; Limoncin, Erika; Sforza, Alessandra; Jannini, Emmanuele A; Maggi, Mario

2015-12-01

The specific determinants and underlying factors linking erectile dysfunction (ED) and premature ejaculation (PE) have yet to be clearly identified. The aim of this study was to review and meta-analyze all available data regarding the link between ED and PE. An extensive Medline Embase and Cochrane search was performed including the following words: "premature ejaculation" and "erectile dysfunction". All observational trials comparing the risk of ED in relation to PE were included. Data extraction was performed independently by two of the authors (G.R, G.C.), and conflicts resolved by the third investigator (M.M.). Out of 474 retrieved articles, 18 were included in the study for a total of 57,229 patients, of which 12,144 (21.2%) had PE. The presence of PE, however defined, was associated with a significant increase in ED risk (odds ratio: 3.68[2.61;5.18]; P < 0.0001). Meta-regression analysis showed that the risk of ED in PE subjects was higher in older individuals as well as in those with a lower level of education and in those who reported a stable relationship less frequently. In addition, subjects with PE and ED more often reported anxiety and depressive symptoms and a lower prevalence of organic associated morbidities, including diabetes mellitus, hypertension and dyslipidemia. All the latter associations were confirmed even after adjustment for age. Finally the risk of PE-related ED increased with the increased proportion of acquired ejaculatory problems (adj r = 0.414; P < 0.0001 after the adjustment for age). In conclusion, the present data showed that ED and PE are not distinctly separate entities, but should be considered from a dimensional point of view. Understanding this dimensional perspective might help sexual health care professionals in providing the most appropriate therapeutic approach to realistically increase patient related outcomes in sexual medicine. © 2015 International Society for Sexual Medicine.

The postoperative Model for End stage Liver Disease score as a predictor of short-term outcome after transplantation of extended criteria donor livers.

PubMed

Benko, Tamas; Gallinat, Anja; Minor, Thomas; Saner, Fuat H; Sotiropoulos, Georgios C; Paul, Andreas; Hoyer, Dieter P

2017-06-01

Recently, the postoperative Model for End stage Liver Disease score (POPMELD) was suggested as a definition of postoperative graft dysfunction and a predictor of outcome after liver transplantation (LT). The aim of the present study was to validate this concept in the context of extended criteria donor (ECD) organs. Single-center prospectively collected data (OPAL study/01/11-12/13) of 116 ECD LTs were utilized. For each recipient, the Model for End stage Liver Disease (MELD) score was calculated for 7 postoperative days (PODs). The ability of international normalized ratio, bilirubin, aspartate aminotransferase, Donor Risk Index, a recent definition of early allograft dysfunction, and the POPMELD was compared to predict 90-day graft loss. Predictive abilities were compared by receiver operating characteristic curves, sensitivity and specificity, and positive and negative predictive values. The median Donor Risk Index was 1.8. In all, 60.3% of recipients were men [median age of 54 (23-68) years]. The median POD1-7 peak-aspartate aminotransferase value was 1052 (194-17 577) U/l. The rate of early allograft dysfunction was 22.4%. The 90-day graft survival was 89.7%. Out of possible predictors of the 90-day graft loss MELD on POD5 was the best predictor of outcome (area under the curve=0.84). A MELD score of 16 or more on POD5 predicted the 90-day graft loss with a specificity of 80.8%, a sensitivity of 81.8%, and a positive and negative predictive value of 31 and 97.7%. A MELD score of 16 or more on POD5 is an excellent predictor of outcome in ECD donor LT. Routine evaluation of POPMELD scores might support clinical decision-making and should be reported routinely in clinical trials.

The effect of statins on erectile dysfunction: a meta-analysis of randomized trials.

PubMed

Kostis, John B; Dobrzynski, Jeanne M

2014-07-01

Erectile dysfunction (ED) is common in older men, especially those with comorbidities such as diabetes and atherosclerotic disease, conditions where statins are frequently prescribed. To examine the effect of statin therapy on ED using the five-item version of the International Inventory of Erectile Function (IIEF). We performed a random-effects meta-analysis of studies identified by a systematic search of MEDLINE, Web of Knowledge, the Cochrane Database, and ClinicalTrials.gov. Examination of the 186 retrieved citations resulted in the selection of 11 randomized trials for inclusion in the meta-analysis. Change in the IIEF score. IIEF increased by 3.4 points (95% CI 1.7-5.0, P = 0.0001) with statins compared to control. This effect remained statistically significant after multiple sensitivity analyses, including analysis for publication bias, a cumulative meta-analysis, and 11 repeated analyses with each study omitted sequentially. The increase in IIEF with statins was approximately one-third to one-half of that previously reported with phosphodiesterase-5 inhibitors and larger than the effect of lifestyle modification. Metaregression showed an increase in benefit with decreasing lipophilicity. The average age of participants and the degree of LDL cholesterol lowering did not alter the effect on IIEF. Statins cause a clinically relevant improvement of erectile function as measured by the five-item version of the IIEF. © 2014 International Society for Sexual Medicine.

Erectile dysfunction

PubMed Central

Yafi, Faysal A.; Jenkins, Lawrence; Albersen, Maarten; Corona, Giovanni; Isidori, Andrea M.; Goldfarb, Shari; Maggi, Mario; Nelson, Christian J.; Parish, Sharon; Salonia, Andrea; Tan, Ronny; Mulhall, John P.; Hellstrom, Wayne J. G.

2016-01-01

Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Roles for nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed. Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction. Minimally invasive interventions to relieve the symptoms of erectile dysfunction include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices. Surgical therapies are reserved for the subset of patients who have contraindications to these nonsurgical interventions, those who experience adverse effects from (or are refractory to) medical therapy and those who also have penile fibrosis or penile vascular insufficiency. Erectile dysfunction can have deleterious effects on a man’s quality of life; most patients have symptoms of depression and anxiety related to sexual performance. These symptoms, in turn, affect his partner’s sexual experience and the couple’s quality of life. This Primer highlights numerous aspects of erectile dysfunction, summarizes new treatment targets and ongoing preclinical studies that evaluate new pharmacotherapies, and covers the topic of regenerative medicine, which represents the future of sexual medicine. PMID:27188339

Robot-supported upper limb training in a virtual learning environment : a pilot randomized controlled trial in persons with MS.

PubMed

Feys, Peter; Coninx, Karin; Kerkhofs, Lore; De Weyer, Tom; Truyens, Veronik; Maris, Anneleen; Lamers, Ilse

2015-07-23

Despite the functional impact of upper limb dysfunction in multiple sclerosis (MS), effects of intensive exercise programs and specifically robot-supported training have been rarely investigated in persons with advanced MS. To investigate the effects of additional robot-supported upper limb training in persons with MS compared to conventional treatment only. Seventeen persons with MS (pwMS) (median Expanded Disability Status Scale of 8, range 3.5-8.5) were included in a pilot RCT comparing the effects of additional robot-supported training to conventional treatment only. Additional training consisted of 3 weekly sessions of 30 min interacting with the HapticMaster robot within an individualised virtual learning environment (I-TRAVLE). Clinical measures at body function (Hand grip strength, Motricity Index, Fugl-Meyer) and activity (Action Research Arm test, Motor Activity Log) level were administered before and after an intervention period of 8 weeks. The intervention group were also evaluated on robot-mediated movement tasks in three dimensions, providing active range of motion, movement duration and speed and hand-path ratio as indication of movement efficiency in the spatial domain. Non-parametric statistics were applied. PwMS commented favourably on the robot-supported virtual learning environment and reported functional training effects in daily life. Movement tasks in three dimensions, measured with the robot, were performed in less time and for the transporting and reaching movement tasks more efficiently. There were however no significant changes for any clinical measure in neither intervention nor control group although observational analyses of the included cases indicated large improvements on the Fugl-Meyer in persons with more marked upper limb dysfunction. Robot-supported training lead to more efficient movement execution which was however, on group level, not reflected by significant changes on standard clinical tests. Persons with more marked upper limb dysfunction may benefit most from additional robot-supported training, but larger studies are needed. This trial is registered within the registry Clinical Trials GOV ( NCT02257606 ).

Effect of Levosimendan on Renal Outcome in Cardiac Surgery Patients With Chronic Kidney Disease and Perioperative Cardiovascular Dysfunction: A Substudy of a Multicenter Randomized Trial.

PubMed

Zangrillo, Alberto; Alvaro, Gabriele; Belletti, Alessandro; Pisano, Antonio; Brazzi, Luca; Calabrò, Maria G; Guarracino, Fabio; Bove, Tiziana; Grigoryev, Evgeny V; Monaco, Fabrizio; Boboshko, Vladimir A; Likhvantsev, Valery V; Scandroglio, Anna M; Paternoster, Gianluca; Lembo, Rosalba; Frassoni, Samuele; Comis, Marco; Pasyuga, Vadim V; Navalesi, Paolo; Lomivorotov, Vladimir V

2018-02-26

Acute kidney injury (AKI) occurs frequently after cardiac surgery. Levosimendan might reduce the incidence of AKI in patients undergoing cardiac surgery. The authors investigated whether levosimendan administration could reduce AKI incidence in a high-risk cardiac surgical population. Post hoc analysis of a multicenter randomized trial. Cardiac surgery operating rooms and intensive care units of 14 centers in 3 countries. The study comprised 90 patients who underwent mitral valve surgery with an estimated glomerular filtration rate <60 mL/min/1.73 m 2 and perioperative myocardial dysfunction. Patients were assigned randomly to receive levosimendan (0.025-0.2 μg/kg/min) or placebo in addition to standard inotropic treatment. Forty-six patients were assigned to receive levosimendan and 44 to receive placebo. Postoperative AKI occurred in 14 (30%) patients in the levosimendan group versus 23 (52%) in the placebo group (absolute difference -21.8; 95% confidence interval -41.7 to -1.97; p = 0.035). The incidence of major complications also was lower (18 [39%]) in the levosimendan group versus that in the placebo group (29 [66%]) (absolute difference -26.8 [-46.7 to -6.90]; p = 0.011). A trend toward lower serum creatinine at intensive care unit discharge was observed in the levosimendan group (1.18 [0.99-1.49] mg/dL) versus that in the placebo group (1.39 [1.05-1.76] mg/dL) (95% confidence interval -0.23 [-0.49 to 0.01]; p = 0.07). Levosimendan may improve renal outcome in cardiac surgery patients with chronic kidney disease undergoing mitral valve surgery who develop perioperative myocardial dysfunction. Results of this exploratory analysis should be investigated in future properly designed randomized controlled trials. Copyright © 2018 Elsevier Inc. All rights reserved.

Short- and Medium-Term Outcomes After Transcatheter Pulmonary Valve Placement in the Expanded Multicenter US Melody Valve Trial

PubMed Central

McElhinney, Doff B.; Hellenbrand, William E.; Zahn, Evan M.; Jones, Thomas K.; Cheatham, John P.; Lock, James E.; Vincent, Julie A.

2014-01-01

Background Transcatheter pulmonary valve placement is an emerging therapy for pulmonary regurgitation and right ventricular outflow tract obstruction in selected patients. The Melody valve was recently approved in the United States for placement in dysfunctional right ventricular outflow tract conduits. Methods and Results From January 2007 to August 2009, 136 patients (median age, 19 years) underwent catheterization for intended Melody valve implantation at 5 centers. Implantation was attempted in 124 patients; in the other 12, transcatheter pulmonary valve placement was not attempted because of the risk of coronary artery compression (n=6) or other clinical or protocol contraindications. There was 1 death from intracranial hemorrhage after coronary artery dissection, and 1 valve was explanted after conduit rupture. The median peak right ventricular outflow tract gradient was 37 mm Hg before implantation and 12 mm Hg immediately after implantation. Before implantation, pulmonary regurgitation was moderate or severe in 92 patients (81% with data); no patient had more than mild pulmonary regurgitation early after implantation or during follow-up (≥1 year in 65 patients). Freedom from diagnosis of stent fracture was 77.8±4.3% at 14 months. Freedom from Melody valve dysfunction or reintervention was 93.5±2.4% at 1 year. A higher right ventricular outflow tract gradient at discharge (P=0.003) and younger age (P=0.01) were associated with shorter freedom from dysfunction. Conclusions In this updated report from the multicenter US Melody valve trial, we demonstrated an ongoing high rate of procedural success and encouraging short-term valve function. All reinterventions in this series were for right ventricular outflow tract obstruction, highlighting the importance of patient selection, adequate relief of obstruction, and measures to prevent and manage stent fracture. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00740870. PMID:20644013

Executive Function, Survival, and Hospitalization in Chronic Obstructive Pulmonary Disease. A Longitudinal Analysis of the National Emphysema Treatment Trial (NETT).

PubMed

Dodd, James W; Novotny, Paul; Sciurba, Frank C; Benzo, Roberto P

2015-10-01

Cognitive dysfunction has been demonstrated in chronic obstructive pulmonary disease (COPD), but studies are limited to cross-sectional analyses or incompletely characterized populations. We examined longitudinal changes in sensitive measures of executive function in a well-characterized population of patients with severe COPD. This study was performed on patients enrolled in the National Emphysema Treatment Trial. To assess executive function, we analyzed trail making (TM) A and B times at enrollment in the trial (2,128 patients), and at 12 (731 patients) and 24 months (593 patients) after enrollment, adjusted for surgery, marriage status, age, education, income, depression, PaO2, PaCO2, and smoking. Associations with survival and hospitalizations were examined using Cox regression and linear regression models. The average age of the patients was 66.4 years, and the average FEV1 was 23.9% predicted. At the time of enrolment, 38% had executive dysfunction. Compared with those who did not, these patients were older, less educated, had higher oxygen use, higher PaCO2, worse quality of life as measured by the St. George's Respiratory Quotient, reduced well-being, and lower social function. There was no significant change over 2 years in TM A or B times after adjustment for covariables. Changes in TM B times were modestly associated with survival, but changes in TM B-A times were not. Changes in TM scores were not associated with frequency of hospitalization. Lung function, PaO2, smoking, survival, and hospitalizations were not significantly different in those with executive dysfunction. In this large population of patients with severe emphysema and heavy cigarette smoking exposure, there was no significant decline over 2 years in cognitive executive function as measured by TM tests. There was no association between executive function impairment and frequency of hospitalization, and there was a possible modest association with survival. It is plausible that cerebrovascular comorbidities explain previously described cognitive pathology in COPD.

Oxidative stress treatment for clinical trials in neurodegenerative diseases.

PubMed

Ienco, Elena Caldarazzo; LoGerfo, Annalisa; Carlesi, Cecilia; Orsucci, Daniele; Ricci, Giulia; Mancuso, Michelangelo; Siciliano, Gabriele

2011-01-01

Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine.

Nonprescription analgesics and their use in solid-organ transplantation: a review.

PubMed

Gabardi, Steven; Luu, Linh

2004-09-01

To review the pharmacology, adverse events, drug interactions, and use of the nonprescription analgesics in solid-organ transplant recipients. Studies evaluating nonprescription analgesics in solid-organ transplantation were considered for evaluation. English-language studies were selected for inclusion. Nonprescription analgesics (aspirin, choline salicylate, magnesium salicylate, sodium salicylate, ibuprofen, ketoprofen, naproxen sodium, and acetaminophen) are the most commonly purchased over-the-counter agents in the United States. These agents, although generally considered safe, have been associated with a number of toxicities. The salicylates and nonsteroidal anti-inflammatory drugs have been associated with gastrointestinal damage, hematologic changes, liver and kidney dysfunction, and breathing difficulties. Acetaminophen has been shown to induce hematologic changes and liver and renal dysfunction. A closer look at the nonprescription analgesics reveals their potential for harm when used by solid-organ transplant recipients. In this patient population, the salicylates and nonsteroidal anti-inflammatory drugs should generally be avoided if possible, because of their potential toxicities, especially renal dysfunction. Low-dose aspirin, for the prevention of cardiovascular and cardiocerebral events, appears to be safe, but patients must still be followed closely. Acetaminophen is generally considered the nonprescription analgesic and antipyretic of choice in transplant recipients because of its favorable toxicity profile. However, it is imperative that patients and transplant practitioners are aware that this agent is not without toxicities and proper monitoring is advised.

Serum cytochrome c level as a prognostic indicator in patients with systemic inflammatory response syndrome.

PubMed

Adachi, Naoto; Hirota, Masahiko; Hamaguchi, Masamichi; Okamoto, Kazufumi; Watanabe, Keisuke; Endo, Fumio

2004-04-01

Apoptosis may play an important role in the development of systemic inflammatory response syndrome (SIRS) and progression to multiple organ dysfunction syndrome (MODS). To quantify the extent of apoptosis in these morbidities, we developed a sandwich ELISA system to measure serum cytochrome c (cyt-c) levels and we investigated the prognostic significance of cyt-c concentration in SIRS/MODS patients. Cyt-c concentrations in patients with SIRS (n=53) with or at risk for MODS were measured and compared with those of control subjects (n=14). Cyt-c concentrations in SIRS/MODS patients increased (0.24-210 ng/ml), whereas those in control subjects were under detection limits (0.1 ng/ml). Cyt-c concentrations in non-survivors increased significantly compared with those in survivors both on the day of admission and on the fifth hospital day. A significant positive correlation was found between cyt-c concentration and two representative organ dysfunction scores, APACHE II and multi-organ failure (MOF) score. Cyt-c concentrations increased earlier than MOF score during the exacerbation phase and rapidly decreased during the convalescence phase in a survivor, but the level continued to be high in a non-survivor. Determination of serum cyt-c concentrations may be useful to assess the severity of organ dysfunction and to predict the prognosis of SIRS/MODS patients.

Pelvic organ prolapse (POP) surgery: the evidence for the repairs.

PubMed

Gomelsky, Alex; Penson, David F; Dmochowski, Roger R

2011-06-01

What is known on the subject? and What does the study add? Substantial experience of the outcomes has been gathered regarding the acute and sub-acute experience with various types of corrective procedures for POP. These include long-term POP correction as well as more recent recognition of improvement in functional disorders associated with POP such as UI, colorectal dysfunction, and sexual dysfunction. Long-term follow-up is available for some of the older types of interventions and current multicentre trials are being accrued with longer term follow-up for new interventions including mesh-type repairs. The study adds a condensed and summarized version of the current literature regarding the various interventions for POP and also provides an overview of the current controversies and areas where knowledge is incomplete and in need of further elaboration for definitive answers regarding optimization of surgical care for POP. Our aim is to summarise the available data on the transvaginal placement of synthetic mesh for pelvic organ prolapse (POP) repair, with a focus on the outcomes and complications of commercial POP-repair kits. As the stability and durability of autologous tissues may be questionable, nonabsorbable, synthetic materials are an attractive alternative for providing additional support during POP surgery. These materials are not novel, and most have been used for many years in surgical applications, e.g. hernia repairs. While theoretically appealing, the implantation of synthetic mesh in the pelvis may be associated with inherent adverse consequences, such as erosion, extrusion, and infection. Additionally, the routine use of these materials may carry potential long-term complications, such as dyspareunia, chronic pelvic pain, and vaginal distortion. The success and failure of mesh-augmented POP repair is related not only to the synthetic material itself, but also to patient- and surgeon-related factors. Recent warnings by the USA Food and Drug Administration and other groups regarding adverse events further complicate the decision to use synthetic mesh. © 2011 THE AUTHORS; BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

The budget impact and cost-effectiveness of defibrotide for treatment of veno-occlusive disease with multi-organ dysfunction in patients post-hematopoietic stem cell transplant.

PubMed

Veenstra, David L; Guzauskas, Gregory F; Villa, Kathleen F; Boudreau, Denise M

2017-05-01

A Phase-3 study of defibrotide compared with historical controls demonstrated a 23% improvement in 100-day survival post-hematopoietic stem cell transplantation (HSCT) among patients with veno-occlusive disease with multi-organ dysfunction (VOD with MOD). To estimate the budget impact and cost-effectiveness of introducing defibrotide to a transplant center. The authors developed a budget impact model from the perspective of a bone-marrow transplant center. It was estimated that 2.3% of adults and 4.2% of children would develop VOD with MOD following HSCT based on a retrospective hospital database analysis and the effect that treating patients with defibrotide would have on costs for adult and pediatric centers was estimated. A cost-utility analysis (CUA) was also developed to capture the long-term cost-effectiveness of defibrotide. Projected life expectancies in the two groups were estimated based on trial data, transplant registry data, studies of long-term survival among HSCT patients, and US population life-tables. There was an estimated 3% increase ($330,706) per year in total adult transplantation center costs associated with adopting defibrotide, and a <1% increase ($106,385) for pediatric transplant centers, assuming 100 transplants per year. In the CUA, the lifetime increase in cost per patient was $106,928, life expectancy increased by 3.74 years, and quality-adjusted life-years (QALYs) increased by 2.24. The incremental cost-effectiveness ratio (ICER) was $47,736 per QALY gained; 88% probability defibrotide was cost-effective at a $100,000/QALY threshold. The budget impact of defibrotide for a transplant center is relatively modest compared to the overall cost of transplantation. Defibrotide provides an important survival advantage for VOD with MOD patients, and the life years gained lead to defibrotide being highly cost-effective.

Biomarkers of activation of renin-angiotensin-aldosterone system in heart failure: how useful, how feasible?

PubMed

Emdin, Michele; Fatini, Cinzia; Mirizzi, Gianluca; Poletti, Roberta; Borrelli, Chiara; Prontera, Concetta; Latini, Roberto; Passino, Claudio; Clerico, Aldo; Vergaro, Giuseppe

2015-03-30

Renin-angiotensin-aldosterone system (RAAS), participated by kidney, liver, vascular endothelium, and adrenal cortex, and counter-regulated by cardiac endocrine function, is a complex endocrine system regulating systemic functions, such as body salt and water homeostasis and vasomotion, in order to allow the accomplishment of physiological tasks, such as orthostasis, physical and emotional stimuli, and to react towards the hemorrhagic insult, in tight conjunction with other neurohormonal axes, namely the sympathetic nervous system, the endothelin and vasopressin systems. The systemic as well as the tissue RAAS are also dedicated to promote tissue remodeling, particularly relevant after damage, when chronic activation may configure as a maladaptive response, leading to fibrosis, hypertrophy and apoptosis, and organ dysfunction. RAAS activation is a fingerprint of systemic arterial hypertension, kidney dysfunction, vascular atherosclerotic disease, and is definitely an hallmark of heart failure, which rapidly shifts from organ disease to a disorder of neurohormonal regulatory systems. Chronic RAAS activation is an indirect or direct target of most effective pharmacological treatments in heart failure, such as beta-blockers, inhibitors of angiotensin converting enzyme, angiotensin receptor blockers, direct renin inhibitors, and mineralocorticoid receptor blockers. Biomarkers of RAAS activation are available, with different feasibility and accuracy, such as plasma renin activity, renin, angiotensin II, and aldosterone, which all accompany the increasing clinical severity of heart failure disease, and are well recognized prognostic factors, even in patients with optimal therapy. Polymorphisms influencing the expression and activity of RAAS pathways have been recognized as clinically relevant biomarkers, likely influencing either the individual clinical phenotype, or the response to drugs. This solid, growing evidence strongly suggests the rationale for the use of biomarkers of the RAAS activation, as a guide to tailor individual therapy in the current practice, and their implementation as a rule-in marker for future trials on novel drugs in the heart failure setting. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of the Causes of Erectile Dysfunction in Patients Undergoing Penile Doppler Ultrasonography in Pakistan

PubMed Central

Khanzada, Usman; Khan, Sohail Ahmed; Hussain, Munawar; Adel, Hatem; Masood, Kamran; Manohar, Murli

2017-01-01

Purpose In patients with erectile dysfunction, it is important to differentiate psychogenic from organic causes. Penile Doppler ultrasonography is a relatively inexpensive and minimally invasive tool for this purpose. This study was conducted to evaluate the causes of erectile dysfunction in an adult male population, using penile Doppler ultrasonography. Materials and Methods A retrospective study was conducted in a single center. All patients who presented with complaints of erectile dysfunction and underwent penile Doppler ultrasonography between July 2014 and June 2016 were included in this study. All examinations were performed using GE Voluson S6 and GE Logiq P5 devices. Following baseline scans, an intracavernosal injection of 20 µg of prostaglandin E1 was given. Peak systolic and end diastolic velocities were measured in each cavernosal artery. Patients with a peak systolic velocity of <25 cm/s were considered to have arterial insufficiency, while an end diastolic velocity of >5 cm/s was considered to indicate venous incompetence. Results Out of 97 patients (mean age, 37.09±11.59 years; range, 19~69 years), 50 patients (51.5%) had normal findings, 24 patients (24.7%) had arterial insufficiency, 15 patients (15.5%) had a venous leak, and 8 patients (8.2%) patients had arterial insufficiency with a venous leak. Psychogenic erectile dysfunction was significantly higher among patients aged ≤40 years, while arterial insufficiency with or without a venous leak was significantly higher among patients aged >40 years (p=0.022). Conclusions A majority of the studied individuals demonstrated no organic cause of erectile dysfunction, thus confirming a high prevalence of the psychogenic etiology, particularly in relatively young individuals. PMID:28459144

Productivity benefits of minimally invasive surgery in patients with chronic sacroiliac joint dysfunction.

PubMed

Saavoss, Josh D; Koenig, Lane; Cher, Daniel J

2016-01-01

Sacroiliac joint (SIJ) dysfunction is associated with a marked decrease in quality of life. Increasing evidence supports minimally invasive SIJ fusion as a safe and effective procedure for the treatment of chronic SIJ dysfunction. The impact of SIJ fusion on worker productivity is not known. Regression modeling using data from the National Health Interview Survey was applied to determine the relationship between responses to selected interview questions related to function and economic outcomes. Regression coefficients were then applied to prospectively collected, individual patient data in a randomized trial of SIJ fusion (INSITE, NCT01681004) to estimate expected differences in economic outcomes across treatments. Patients who receive SIJ fusion using iFuse Implant System(®) have an expected increase in the probability of working of 16% (95% confidence interval [CI] 11%-21%) relative to nonsurgical patients. The expected change in earnings across groups was US $3,128 (not statistically significant). Combining the two metrics, the annual increase in worker productivity given surgical vs nonsurgical care was $6,924 (95% CI $1,890-$11,945). For employees with chronic, severe SIJ dysfunction, minimally invasive SIJ fusion may improve worker productivity compared to nonsurgical treatment.

Increased risk of organic erectile dysfunction in patients with chronic fatigue syndrome: a nationwide population-based cohort study.

PubMed

Chao, C-H; Chen, H-J; Wang, H-Y; Li, T-C; Kao, C-H

2015-07-01

Chronic fatigue syndrome (CFS) is a complex disorder characterized by profound and persistent fatigue and several comorbidities. CFS was previously reported to be associated with female sexual dysfunction. We propose that CFS might also be associated with organic erectile dysfunction (organic ED). We conducted a retrospective cohort study by using data from the National Health Insurance (NHI) Research Database. We identified 2156 male patients who were newly diagnosed with CFS between January 1, 2003 and December 31, 2006. After excluding those younger than 20 years and prevalent cases, 1976 patients were subjected to analysis, and 7904 people served as healthy controls. All study subjects were followed up from the index date to the date of organic ED diagnosis, withdrawal from the NHI program, or the end of 2011. Compared with the non-CFS cohort, the incidence density rate of organic ED was 1.88-fold higher than that in the CFS cohort (3.23 vs. 1.73 per 1000 person-years) with an adjusted hazard ratio (HR) of 1.88 (95% CI = 1.26-2.81) when adjusting for sex and comorbidities. The combined impacts of patients with CFS and cardiovascular disease (CVD), diabetes mellitus (DM), chronic kidney disease (CKD), depression, and anxiety showed a significant by joint association with organic ED risk compared with patients with no CFS and no counterpart comorbidity. The greatest magnitude of adjusted HR of ED for CFS was observed in individuals without any comorbidity (3.87, 1.95-7.66). The incidence of organic ED is higher among males aged 40 years and over for both CFS and non-CFS cohorts. As the number of comorbidity increases, the incidence of organic ED increases in males without CFS. Higher incidence of organic ED was observed in males with CVD, DM, CKD, depression, or anxiety for both CFS and non-CFS cohorts. © 2015 American Society of Andrology and European Academy of Andrology.

Balanced crystalloids versus saline in the intensive care unit: study protocol for a cluster-randomized, multiple-crossover trial.

PubMed

Semler, Matthew W; Self, Wesley H; Wang, Li; Byrne, Daniel W; Wanderer, Jonathan P; Ehrenfeld, Jesse M; Stollings, Joanna L; Kumar, Avinash B; Hernandez, Antonio; Guillamondegui, Oscar D; May, Addison K; Siew, Edward D; Shaw, Andrew D; Bernard, Gordon R; Rice, Todd W

2017-03-16

Saline, the intravenous fluid most commonly administered to critically ill adults, contains a high chloride content, which may be associated with acute kidney injury and death. Whether using balanced crystalloids rather than saline decreases the risk of acute kidney injury and death among critically ill adults remains unknown. The Isotonic Solutions and Major Adverse Renal Events Trial (SMART) is a pragmatic, cluster-level allocation, cluster-level crossover trial being conducted between 1 June 2015 and 30 April 2017 in five intensive care units at Vanderbilt University Medical Center in Nashville, TN, USA. SMART compares saline (0.9% sodium chloride) with balanced crystalloids (clinician's choice of lactated Ringer's solution or Plasma-Lyte A®). Each intensive care unit is assigned to provide either saline or balanced crystalloids each month, with the assigned crystalloid alternating monthly over the course of the trial. All adults admitted to participating intensive care units during the study period are enrolled and followed until hospital discharge or 30 days after enrollment. The anticipated enrollment is approximately 14,000 patients. The primary outcome is Major Adverse Kidney Events within 30 days-the composite of in-hospital death, receipt of new renal replacement therapy, or persistent renal dysfunction (discharge creatinine ≥200% of baseline creatinine). Secondary clinical outcomes include in-hospital mortality, intensive care unit-free days, ventilator-free days, vasopressor-free days, and renal replacement therapy-free days. Secondary renal outcomes include new renal replacement therapy receipt, persistent renal dysfunction, and incidence of stage 2 or higher acute kidney injury. This ongoing pragmatic trial will provide the largest and most comprehensive comparison to date of clinical outcomes with saline versus balanced crystalloids among critically ill adults. For logistical reasons, SMART was prospectively registered separately for the medical ICU (SMART-MED; ClinicalTrials.gov identifier: NCT02444988 ; registered on 11 May 2015; date of first patient enrollment: 1 June 2015) and the nonmedical ICUs (SMART-SURG; ClinicalTrials.gov identifier: NCT02547779 ; registered on 9 September 2015; date of first patient enrollment: 1 October 2015).

Pathophysiology of the Gut and the Microbiome in the Host Response.

PubMed

Lyons, John D; Coopersmith, Craig M

2017-03-01

To describe and summarize the data supporting the gut as the motor driving critical illness and multiple organ dysfunction syndrome presented at the National Institute of Child Health and Human Development MODS Workshop (March 26-27, 2015). Summary of workshop keynote presentation. Not applicable. Presented by an expert in the field, the data assessing the role of gastrointestinal dysfunction driving critical illness were described with a focus on identifying knowledge gaps and research priorities. Summary of presentation and discussion supported and supplemented by relevant literature. The understanding of gut dysfunction in critical illness has evolved greatly over time, and the gut is now often considered as the "motor" of critical illness. The association of the gut with critical illness is supported by both animal models and clinical studies. Initially, the association between gut dysfunction and critical illness focused primarily on bacterial translocation into the bloodstream. However, that work has evolved to include other gut-derived products causing distant injury via other routes (e.g., lymphatics). Additionally, alterations in the gut epithelium may be associated with critical illness and influence outcomes. Gut epithelial apoptosis, intestinal hyperpermeability, and perturbations in the intestinal mucus layer have all been associated with critical illness. Finally, there is growing evidence that the intestinal microbiome plays a crucial role in mediating pathology in critical illness. Further research is needed to better understand the role of each of these mechanisms and their contribution to multiple organ dysfunction syndrome in children.

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

PubMed Central

2013-01-01

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches. PMID:24289502

Myocardial Hypertrophy and Its Role in Heart Failure with Preserved Ejection Fraction

PubMed Central

Heinzel, Frank R.; Hohendanner, Felix; Jin, Ge; Sedej, Simon; Edelmann, Frank

2015-01-01

Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load and cytokines associated with arterial hypertension, chronic kidney disease, diabetes and other co-morbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood but may include extracellular matrix changes, vascular dysfunction as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca2+ turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound co-morbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training on the other hand, in clinical trials improved exercise tolerance and diastolic function but did not reduce LVH. Thus, current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF. PMID:26183480

Getting the invite list right: a discussion of sepsis severity scoring systems in severe complicated intra-abdominal sepsis and randomized trial inclusion criteria.

PubMed

Tolonen, Matti; Coccolini, Federico; Ansaloni, Luca; Sartelli, Massimo; Roberts, Derek J; McKee, Jessica L; Leppaniemi, Ari; Doig, Christopher J; Catena, Fausto; Fabian, Timothy; Jenne, Craig N; Chiara, Osvaldo; Kubes, Paul; Kluger, Yoram; Fraga, Gustavo P; Pereira, Bruno M; Diaz, Jose J; Sugrue, Michael; Moore, Ernest E; Ren, Jianan; Ball, Chad G; Coimbra, Raul; Dixon, Elijah; Biffl, Walter; MacLean, Anthony; McBeth, Paul B; Posadas-Calleja, Juan G; Di Saverio, Salomone; Xiao, Jimmy; Kirkpatrick, Andrew W

2018-01-01

Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent. An evaluation of abilities of recognized predictive systems to recognize SCIAS patients was conducted using an existing intra-abdominal sepsis (IAS) database. All consecutive adult patients with a diffuse secondary peritonitis between 2012 and 2013 were collected from a quaternary care hospital in Finland, excluding appendicitis/cholecystitis. From this retrospectively collected database, a target population (93) of those with either ICU admission or mortality were selected. The performance metrics of the Third Consensus Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition, Infection, Response, and Organ dysfunction (CPIRO) score were all tested for their discriminant ability to identify this subgroup with SCIAS and to predict mortality. Predictive systems with an area under-the-receiving-operating characteristic (AUC) curve > 0.8 included SOFA, Sepsis-3 definitions, APACHE II, WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest identification rates were SOFA score ≥ 2 (78.4%), followed by the WSESSSS score ≥ 8 (73.1%), SOFA ≥ 3 (75.2%), and APACHE II ≥ 14 (68.8%) identification. Combining the Sepsis-3 septic-shock definition and WSESSS ≥ 8 increased detection to 80%. Including CPIRO score ≥ 3 increased this to 82.8% (Sensitivity-SN; 83% Specificity-SP; 74%. Comparatively, SOFA ≥ 4 and WSESSSS ≥ 8 with or without septic-shock had 83.9% detection (SN; 84%, SP; 75%, 25% mortality). No one scoring system behaves perfectly, and all are largely dominated by organ dysfunction. Utilizing combinations of SOFA, CPIRO, and WSESSSS scores in addition to the Sepsis-3 septic shock definition appears to offer the widest "inclusion-criteria" to recognize patients with a high chance of mortality and ICU admission. https://clinicaltrials.gov/ct2/show/NCT03163095; Registered on May 22, 2017.

Balance of autonomic nervous system in children having signs of endothelial dysfunction, that were born and are domiciled in contaminated territories.

PubMed

Kondrashova, V G; Kolpakov, I E; Vdovenko, V Yu; Leonovych, O S; Lytvynets, O M; Stepanova, E I

2014-09-01

Objective. The study examined the features of functional state of the autonomic nervous system in children having endothelial dysfunction and permanently residing in contaminated areas. Materials and methods. Clinical and instrumental examination of 101 children aged 7-18 years that were born and are domiciled in contaminated territories, including 37 persons with signs of endothelial dysfunction (subgroup IA) and 64 ones with no signs of endothelial dysfunction (IB subgroup) was conducted. The control group being comparable to the subgroups IA and IB by age, gender and clinical examination results included 37 children neither been domiciled in contaminated areas nor were belonging to the contingent of Chornobyl accident survivors. There were 20 apparently healthy children also examined. Results. Due to peculiarities of physiological pathways providing adaptive responses the children having signs of endothelial dysfunction are characterized by a more pronounced dysregulation of autonomous nervous system both in a resting state and under a functional load simulation, and also by a high strain of adaptation pathways. The lack of autonomous support of cardiovascular system is caused by inadequate adaptive responses of both central regulatory bodies (hypothalamus, vasomotor center) and peripheral receptors. Mainly the failure of segmental autonomous (parasympathetic) structures was revealed. The mode of their response to stress in this case corresponds to that in healthy individuals but at a lower functional level. There is a reduced aerobic capacity of the organism by the Robinson index, contributing to low adaptive range to non-specific stress in children being domiciled on contaminated territories including children having the endothelial dysfunction. Conclusions. Endothelial dysfunction was associated with more pronounced manifestations of autonomic dysregulation and reduced aerobic capacity of the organism being the risk factors of development of a range of somatic diseases requiring the development of prevention measures in children permanently residing in contaminated areas. autonomous nervous system balance, endothelial dysfunction, children, Chornobyl accident. V. G. Kondrashova, I. E. Kolpakov, V. Yu. Vdovenko, O. S. Leonovych, O. M. Lytvynets, E. I. Stepanova.

[Which organization for the management of thoracic cancer? Results from a French survey in Rhône-Alpes region].

PubMed

Couraud, S; Fournel, P; Moro-Sibilot, D; Pérol, M; Souquet, P-J

2012-02-01

This survey, conducted in Rhône-Alpes region (France), aims to better understand the actual conditions of practice in thoracic oncology. A questionnaire was distributed to all oncologists, pulmonologists, radiotherapy physicians and thoracic surgeons in the region. Of 401 questionnaires, the response rate was 56%. Among the responders 46% reported exercising the Thoracic Oncology (TO). Most physicians practicing TO are pulmonologists (62%). The majority (45%) are engaged in secondary hospital or university hospital (27%). However, practitioners with the most important activity exerts in university hospitals and cancer centre (71% of physicians practicing in secondary hospitals and 75% of those in private practice reported to manage fewer than 80 new NSCLC cases per year in structure). Furthermore, 91% are regularly involved in a multidisciplinary team. Radiation oncologist, pulmonologists and thoracic surgeons are assiduous to these meeting; however radiologists and, to a lesser extent, pathologists are less attentive. Moreover, 92% of practitioners belong to cancer networks. Similarly, over one third of working together in a cooperative clinical research institution and nearly half are involved in clinical trials (with nearly half in secondary hospital). These results highlight the reality of practice in Rhône-Alpes and will serve as the basis for coordinating authorities to correct dysfunctions or monitor certain activities of interest (clinical trials). Copyright © 2011 Elsevier Masson SAS. All rights reserved.

The Autodigestion Hypothesis for Shock and Multi-organ Failure

PubMed Central

Schmid-Schönbein, Geert W.; Chang, Marisol

2013-01-01

An important medical problem with high mortality is shock, sepsis and multi-organ failure. They have currently no treatments other than alleviation of symptoms. Shock is accompanied by strong markers for inflammation and involves a cascade of events that leads to failure in organs even if they are not involved in the initial insult. Recent evidence indicates that pancreatic digestive enzymes carried in the small intestine after mixing with ingested food are a major cause for multi-organ failure. These concentrated and relatively non-specific enzymes are usually compartmentalized inside the intestinal lumen as requirement for normal digestion. But after breakdown of the mucosal barrier they leak into the wall of the intestine and start an autodigestion process that includes destruction of villi in the intestine. Digestive enzymes also generate cytotoxic mediators, which together are transported into the systemic circulation via the portal venous system, the intestinal lymphatics and via the peritoneum. They cause various degrees of cell and organ dysfunction that can reach the point of complete organ failure. Blockade of digestive enzymes in the lumen of the intestine in experimental forms of shock serves to reduce breakdown of the mucosal barrier and autodigestion of the intestine, organ dysfunctions and mortality. PMID:23989761

Cardiovascular Disease in Patients with End-Stage Renal Disease on Hemodialysis

PubMed Central

Aoki, Jiro; Ikari, Yuji

2017-01-01

Cardiovascular disease is a major concern for patients with end-stage renal disease (ESRD), especially those on hemodialysis. ESRD patients with coronary artery disease often do not have symptoms or present with atypical symptoms. Coronary lesions in ESRD patients are characterized by increased media thickness, infiltration and activation of macrophages, and marked calcification. Several studies showed worsened clinical outcomes after coronary revascularization, which were dependent on the severity of renal dysfunction. ESRD patients on hemodialysis have the most severe renal dysfunction; thus, the clinical outcomes are worse in these patients than in those with other types of renal dysfunction. Medications for primary or secondary cardiovascular prevention are also insufficient in ESRD patients. Efficacy of drug-eluting stents is inferior in ESRD patients, compared to the excellent outcomes observed in patients with normal renal function. Unsatisfactory outcomes with trials targeting cardiovascular disease in patients with ESRD emphasize a large potential to improve outcomes. Thus, optimal strategies for diagnosis, prevention, and management of cardiovascular disease should be modified in ESRD patients. PMID:29515692

Antioxidants in critical care medicine.

PubMed

Coleman, N A

2001-09-01

Critically ill patients in the intensive care unit (ICU) present with a variety of different pathologies, and mortality is high despite extensive multi-organ supportive treatment. Reactive oxygen species (ROS) are believed to play a pivotal role in the pathophysiology of organ dysfunction in the ICU. In particular, the role of ROS as a final common pathway of cell damage has been increasingly emphasised in the adult respiratory distress syndrome (ARDS), in central nervous system traumatic and hypoxic states, and as a cause of ischaemic neurological deficits after subarachnoid haemorrhage. Measurement of total antioxidant status (TAS) has shown improved survival of patients with high TAS and poorer outcomes for those with lower values. Attempts to supplement endogenous antioxidant defences have not demonstrated clear benefits in randomised clinical trials, and the use of free radical scavenging agents have had similar mixed results. Considering the wide variation in the nature and severity of illness in the intensive care population, it is not surprising that clear evidence of the efficacy of antioxidant therapies in improving survival has not been clearly demonstrated. However, single component therapies for complex pathophysiological processes are rarely successful, and the role of antioxidants in the critically ill should be thought of as only part of a rational and logical therapeutic approach.

Electroacupuncture prevents endothelial dysfunction induced by ischemia-reperfusion injury via a cyclooxygenase-2-dependent mechanism: A randomized controlled crossover trial

PubMed Central

Park, Jimin; Woo, Jong Shin; Leem, Jungtae; Park, Jun Hyeong; Lee, Sanghoon; Chung, Hyemoon; Lee, Jung Myung; Kim, Jin-Bae; Kim, Woo-Shik; Kim, Kwon Sam; Kim, Weon

2017-01-01

Objective Exploring clinically effective methods to reduce ischemia-reperfusion (IR) injury in humans is critical. Several drugs have shown protective effects, but studies using other interventions have been rare. Electroacupuncture (EA) has induced similar protection in several animal studies but no study has investigated how the effects could be translated and reproduced in humans. This study aimed to explore the potential effect and mechanisms of EA in IR-induced endothelial dysfunction in humans. Methods This is a prospective, randomized, crossover, sham-controlled trial consisting of two protocols. Protocol 1 was a crossover study to investigate the effect of EA on IR-induced endothelial dysfunction. Twenty healthy volunteers were randomly assigned to EA or sham EA (sham). Flow mediated dilation (FMD) of the brachial artery (BA), nitroglycerin-mediated endothelial independent dilation, blood pressure before and after IR were measured. In protocol 2, seven volunteers were administered COX-2 inhibitor celecoxib (200 mg orally twice daily) for five days. After consumption, volunteers underwent FMD before and after IR identical to protocol 1. Results In protocol 1, baseline BA diameter, Pre-IR BA diameter and FMD were similar between the two groups (p = NS). After IR, sham group showed significantly blunted FMD (Pre-IR: 11.41 ± 3.10%, Post-IR: 4.49 ± 2.04%, p < 0.001). However, EA protected this blunted FMD (Pre-IR: 10.96 ± 5.30%, Post-IR: 9.47 ± 5.23%, p = NS, p < 0.05 compared with sham EA after IR). In protocol 2, this protective effect was completely abolished by pre-treatment with celecoxib (Pre-IR: 11.05 ± 3.27%; Post-IR: 4.20 ± 1.68%, p = 0.001). Conclusion EA may prevent IR-induced endothelial dysfunction via a COX-2 dependent mechanism. PMID:28591155

Friedreich and dominant ataxias: quantitative differences in cerebellar dysfunction measurements.

PubMed

Tanguy Melac, Audrey; Mariotti, Caterina; Filipovic Pierucci, Antoine; Giunti, Paola; Arpa, Javier; Boesch, Sylvia; Klopstock, Thomas; Müller Vom Hagen, Jennifer; Klockgether, Thomas; Bürk, Katrin; Schulz, Jörg B; Reetz, Kathrin; Pandolfo, Massimo; Durr, Alexandra; Tezenas du Montcel, Sophie

2018-06-01

Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction. We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively. There were 383 patients with Friedreich's ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores. Cerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated. ClinicalTrials.gov: NCT02069509. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PreSERVE-AMI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intracoronary Administration of Autologous CD34+ Cells in Patients With Left Ventricular Dysfunction Post STEMI.

PubMed

Quyyumi, Arshed A; Vasquez, Alejandro; Kereiakes, Dean J; Klapholz, Marc; Schaer, Gary L; Abdel-Latif, Ahmed; Frohwein, Stephen; Henry, Timothy D; Schatz, Richard A; Dib, Nabil; Toma, Catalin; Davidson, Charles J; Barsness, Gregory W; Shavelle, David M; Cohen, Martin; Poole, Joseph; Moss, Thomas; Hyde, Pamela; Kanakaraj, Anna Maria; Druker, Vitaly; Chung, Amy; Junge, Candice; Preti, Robert A; Smith, Robin L; Mazzo, David J; Pecora, Andrew; Losordo, Douglas W

2017-01-20

Despite direct immediate intervention and therapy, ST-segment-elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction≤48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months (P<0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose-dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital (P=0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01495364. © 2016 American Heart Association, Inc.

Five-Week Outcomes From a Dosing Trial of Therapeutic Massage for Chronic Neck Pain

PubMed Central

Sherman, Karen J.; Cook, Andrea J.; Wellman, Robert D.; Hawkes, Rene J.; Kahn, Janet R.; Deyo, Richard A.; Cherkin, Daniel C.

2014-01-01

PURPOSE This trial was designed to evaluate the optimal dose of massage for individuals with chronic neck pain. METHODS We recruited 228 individuals with chronic nonspecific neck pain from an integrated health care system and the general population, and randomized them to 5 groups receiving various doses of massage (a 4-week course consisting of 30-minute visits 2 or 3 times weekly or 60-minute visits 1, 2, or 3 times weekly) or to a single control group (a 4-week period on a wait list). We assessed neck-related dysfunction with the Neck Disability Index (range, 0–50 points) and pain intensity with a numerical rating scale (range, 0–10 points) at baseline and 5 weeks. We used log-linear regression to assess the likelihood of clinically meaningful improvement in neck-related dysfunction (≥5 points on Neck Disability Index) or pain intensity (≥30% improvement) by treatment group. RESULTS After adjustment for baseline age, outcome measures, and imbalanced covariates, 30-minute treatments were not significantly better than the wait list control condition in terms of achieving a clinically meaningful improvement in neck dysfunction or pain, regardless of the frequency of treatments. In contrast, 60-minute treatments 2 and 3 times weekly significantly increased the likelihood of such improvement compared with the control condition in terms of both neck dysfunction (relative risk = 3.41 and 4.98, P = .04 and .005, respectively) and pain intensity (relative risk = 2.30 and 2.73; P = .007 and .001, respectively). CONCLUSIONS After 4 weeks of treatment, we found multiple 60-minute massages per week more effective than fewer or shorter sessions for individuals with chronic neck pain. Clinicians recommending massage and researchers studying this therapy should ensure that patients receive a likely effective dose of treatment. PMID:24615306

Neuromuscular electrical stimulation and the treatment of lower urinary tract dysfunction in multiple sclerosis--a double blind, placebo controlled, randomised clinical trial.

PubMed

McClurg, D; Ashe, R G; Lowe-Strong, A S

2008-01-01

Lower urinary tract dysfunction affects up to 75% of the multiple sclerosis population. Results from our recent Pilot Study (McClurg et al., 2006) indicated that a combined programme of pelvic floor muscle training, electromyography biofeedback and neuromuscular electrical stimulation modalities may alleviate some of the distressing symptoms within this population. This clinical trial aimed to evaluate further the efficacy of these interventions and to establish the benefit of neuromuscular electrical stimulation above and beyond that of EMG biofeedback and pelvic floor muscle training. 74 multiple sclerosis patients who presented with lower urinary tract dysfunction were randomly allocated to one of two groups - Group 1 received Pelvic Floor Muscle Training, Electromyography Biofeedback and Placebo Neuromuscular Electrical Stimulation (n=37), and Group 2 which received Pelvic Floor Muscle Training, Electromyography Biofeedback, and Active Neuromuscular Electrical Stimulation (n=37). Treatment was for nine weeks with outcome measures recorded at weeks 0, 9, 16 and 24. The Primary Outcome Measure was the number of leakage episodes. Within group analysis was by Paired Samples t-test. Group differences were analysed using Repeated Measures Analysis of Variance and Post-hoc tests were used to determine the significance of differences between Groups at each time point. The mean number of incontinence episodes were reduced in Group 2 by 85% (p=0.001) whereas in Group 1 a lesser reduction of 47% (p=0.001) was observed. However, there was a statistically superior benefit in Group 2 when compared to Group 1 (p=0.0028). This superior benefit was evident in all other outcome measures. The addition of Active Neuromuscular Electrical Stimulation to a programme of Pelvic Floor Muscle Training and Electromyography Biofeedback should be considered as a first-line option in alleviating some of the symptoms of lower urinary tract dysfunction associated with multiple sclerosis. (c) 2007 Wiley-Liss, Inc.

Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress.

PubMed

Daiber, Andreas; Münzel, Thomas

2015-10-10

Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3',-5'-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed.

Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress

PubMed Central

2015-01-01

Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed. Antioxid. Redox Signal. 23, 899–942. PMID:26261901

The Comparative Impact of Mindfulness-Based Cancer Recovery (MBCR) and Cognitive Behavior Therapy for Insomnia (CBT-I) on Sleep and Mindfulness in Cancer Patients.

PubMed

Garland, Sheila N; Rouleau, Codie R; Campbell, Tavis; Samuels, Charles; Carlson, Linda E

2015-01-01

Insomnia is an important but often overlooked side effect of cancer. Dysfunctional sleep beliefs have been identified as an important perpetuating factor for insomnia. Mindfulness practice has been demonstrated to improve sleep quality but it is unknown whether these effects relate to changes in dysfunctional sleep beliefs. This study is a secondary analysis of a randomized controlled trial comparing mindfulness-based cancer recovery (MBCR) to cognitive behavior therapy for insomnia (CBT-I) in cancer patients with insomnia. This present analysis compares program impact on mindfulness, dysfunctional sleep beliefs, and insomnia severity clinical cutoffs. Patients (MBCR, n = 32; CBT-I, n = 40) were assessed at baseline, post-program, and 3-month follow-up. Across both groups, patients showed improvements over time in acting with awareness (P = .021) and not judging experiences (P = .023). Changes in dysfunctional sleep beliefs produced by the CBT-I group exceeded those produced by MBCR at post-program and follow-up (P < .001). Acting with awareness, non-judging, and non-reacting were the facets of mindfulness associated with an overall reduction in dysfunctional sleep beliefs. There were no significant differences between the MBCR and CBT-I groups in the percentage of patients exceeding insomnia severity clinical cutoffs at post-program or follow-up. This study supports the use of both CBT-I and MBCR to reduce insomnia severity and suggests the development of mindfulness facets as a method of reducing dysfunctional sleep beliefs. Copyright © 2015 Elsevier Inc. All rights reserved.

Association Between Inflammatory Markers and Progression to Kidney Dysfunction: Examining Different Assessment Windows in Patients With Type 1 Diabetes.

PubMed

Baker, Nathaniel L; Hunt, Kelly J; Stevens, Danielle R; Jarai, Gabor; Rosen, Glenn D; Klein, Richard L; Virella, Gabriel; Lopes-Virella, Maria F

2018-01-01

To determine whether biomarkers of inflammation and endothelial dysfunction are associated with the development of kidney dysfunction and the time frame of their association. Biomarkers were measured at four time points during 28 years of treatment and follow-up in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. In addition to traditional biomarkers of inflammation (C-reactive protein and fibrinogen), we measured interleukin-6 (IL-6) and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1/2), markers of endothelial dysfunction (soluble intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin [sE-selectin]), and fibrinolysis (total and active plasminogen activator inhibitor-1 [PAI-1]). Renal outcomes were defined as progression to incident chronic kidney disease (stage 3 or more severe) or macroalbuminuria (albumin excretion rate ≥300 mg/24 h). Prospective multivariate event-time analyses were used to determine the association of each biomarker with each subsequent event within prespecified intervals (3-year and 10-year windows). Multivariate event-time models indicated that several markers of inflammation (sTNFR-1/2), endothelial dysfunction (sE-selectin), and clotting/fibrinolysis (fibrinogen and PAI-1) are significantly associated with subsequent development of kidney dysfunction. Although some markers showed variations in the associations between the follow-up windows examined, the results indicate that biomarkers (sTNFR-1/2, sE-selectin, PAI-1, and fibrinogen) are associated with progression to chronic kidney disease in both the 3-year and the 10-year windows. Plasma markers of inflammation, endothelial dysfunction, and clotting/fibrinolysis are associated with progression to kidney dysfunction in type 1 diabetes during both short-term and long-term follow-up. © 2017 by the American Diabetes Association.

Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis.

PubMed

Garip, Gokhan; Sarandöl, Emre; Kaya, Ekrem

2013-11-28

To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis (AP). One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included. Patients were classified according to severity of the disease, necrosis ratio and localization. Subjective clinical evaluation and fecal pancreatic elastase-I (FPE-I) were used for exocrine dysfunction evaluation, and oral glucose tolerance test was completed for endocrine dysfunction. The correlation of disease severity, necrosis ratio and localization with exocrine and endocrine dysfunction were investigated. There were 58 male and 51 female patients, and mean age was 56.5 ± 15.7. Of the patients, 35.8% had severe AP (SAP) and 27.5% had pancreatic necrosis. Exocrine dysfunction was identified in 13.7% of the patients [17.9% were in SAP, 11.4% were in mild AP (MAP)] and 34.7% of all of the patients had endocrine dysfunction (56.4% in SAP and 23.2% in MAP). In patients with SAP and necrotizing AP (NAP), FPE-Ilevels were lower than the others (P < 0.05 and 0.001 respectively) and in patients having pancreatic head necrosis or near total necrosis, FPE-1 levels were lower than 200 μg/g stool. Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction. Endocrine dysfunction was more significant in patients with SAP and NAP (P < 0.001). All of the patients in the necrosectomy group had endocrine dysfunction. Patients with SAP, NAP, pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.

Managing Intercultural Teams: The eOrganization Exercise

ERIC Educational Resources Information Center

Humes, Michelle; Reilly, Anne H.

2008-01-01

In today's global environment, intercultural teams may become the most effective teams in an organization when their diversity is managed as an asset. However, because of miscommunication and conflict, intercultural teams often become dysfunctional. This experiential group exercise demonstrates how cultural dimensions such as individualism and…

Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial.

PubMed

Middleton, Sandy; McElduff, Patrick; Ward, Jeanette; Grimshaw, Jeremy M; Dale, Simeon; D'Este, Catherine; Drury, Peta; Griffiths, Rhonda; Cheung, N Wah; Quinn, Clare; Evans, Malcolm; Cadilhac, Dominique; Levi, Christopher

2011-11-12

We assessed patient outcomes 90 days after hospital admission for stroke following a multidisciplinary intervention targeting evidence-based management of fever, hyperglycaemia, and swallowing dysfunction in acute stroke units (ASUs). In the Quality in Acute Stroke Care (QASC) study, a single-blind cluster randomised controlled trial, we randomised ASUs (clusters) in New South Wales, Australia, with immediate access to CT and on-site high dependency units, to intervention or control group. Patients were eligible if they spoke English, were aged 18 years or older, had had an ischaemic stroke or intracerebral haemorrhage, and presented within 48 h of onset of symptoms. Intervention ASUs received treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction with multidisciplinary team building workshops to address implementation barriers. Control ASUs received only an abridged version of existing guidelines. We recruited pre-intervention and post-intervention patient cohorts to compare 90-day death or dependency (modified Rankin scale [mRS] ≥2), functional dependency (Barthel index), and SF-36 physical and mental component summary scores. Research assistants, the statistician, and patients were masked to trial groups. All analyses were done by intention to treat. This trial is registered at the Australia New Zealand Clinical Trial Registry (ANZCTR), number ACTRN12608000563369. 19 ASUs were randomly assigned to intervention (n=10) or control (n=9). Of 6564 assessed for eligibility, 1696 patients' data were obtained (687 pre-intervention; 1009 post-intervention). Results showed that, irrespective of stroke severity, intervention ASU patients were significantly less likely to be dead or dependent (mRS ≥2) at 90 days than control ASU patients (236 [42%] of 558 patients in the intervention group vs 259 [58%] of 449 in the control group, p=0·002; number needed to treat 6·4; adjusted absolute difference 15·7% [95% CI 5·8-25·4]). They also had a better SF-36 mean physical component summary score (45·6 [SD 10·2] in the intervention group vs 42·5 [10·5] in the control group, p=0·002; adjusted absolute difference 3·4 [95% CI 1·2-5·5]) but no improvement was recorded in mortality (21 [4%] of 558 in intervention group and 24 [5%] of 451 in the control group, p=0·36), SF-36 mean mental component summary score (49·5 [10·9] in the intervention group vs 49·4 [10·6] in the control group, p=0·69) or functional dependency (Barthel Index ≥60: 487 [92%] of 532 patients vs 380 [90%] of 423 patients; p=0·44). Implementation of multidisciplinary supported evidence-based protocols initiated by nurses for the management of fever, hyperglycaemia, and swallowing dysfunction delivers better patient outcomes after discharge from stroke units. Our findings show the possibility to augment stroke unit care. National Health & Medical Research Council ID 353803, St Vincent's Clinic Foundation, the Curran Foundation, Australian Diabetes Society-Servier, the College of Nursing, and Australian Catholic University. Copyright © 2011 Elsevier Ltd. All rights reserved.

Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction.

PubMed

Ito, Satomi; Magalska, Adriana; Alcaraz-Iborra, Manuel; Lopez-Atalaya, Jose P; Rovira, Victor; Contreras-Moreira, Bruno; Lipinski, Michal; Olivares, Roman; Martinez-Hernandez, Jose; Ruszczycki, Blazej; Lujan, Rafael; Geijo-Barrientos, Emilio; Wilczynski, Grzegorz M; Barco, Angel

2014-07-18

The interior of the neuronal cell nucleus is a highly organized three-dimensional (3D) structure where regions of the genome that are linearly millions of bases apart establish sub-structures with specialized functions. To investigate neuronal chromatin organization and dynamics in vivo, we generated bitransgenic mice expressing GFP-tagged histone H2B in principal neurons of the forebrain. Surprisingly, the expression of this chimeric histone in mature neurons caused chromocenter declustering and disrupted the association of heterochromatin with the nuclear lamina. The loss of these structures did not affect neuronal viability but was associated with specific transcriptional and behavioural deficits related to serotonergic dysfunction. Overall, our results demonstrate that the 3D organization of chromatin within neuronal cells provides an additional level of epigenetic regulation of gene expression that critically impacts neuronal function. This in turn suggests that some loci associated with neuropsychiatric disorders may be particularly sensitive to changes in chromatin architecture.

Community Organizing for Database Trial Buy-In by Patrons

ERIC Educational Resources Information Center

Pionke, J. J.

2015-01-01

Database trials do not often garner a lot of feedback. Using community-organizing techniques can not only potentially increase the amount of feedback received but also deepen the relationship between the librarian and his or her constituent group. This is a case study of the use of community-organizing techniques in a series of database trials for…

Sildenafil citrate for erectile dysfunction in patients with multiple sclerosis.

PubMed

Xiao, Yousheng; Wang, Jin; Luo, Hongye

2012-04-18

Erectile dysfunction (ED) is a common sexual disease in male patients with multiple sclerosis (MS). Sildenafil citrate is considered as an effective drug in the treatment of male ED in the general population, but it has not been systematically reviewed in patients with MS. To assess the efficacy and safety of sildenafil citrate for ED in patients with MS. We searched the Cochrane (November 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4 of 4, 2011), MEDLINE (PubMed) (January 1966 to November 2011), EMBASE (January 1974 to November 2011) and the China Biological Medicine Database (CBM) (1979 to November 2011). We searched trials registers and conference proceedings and contacted pharmaceutical company and authors of included studies for additional data. There were no language restrictions. Randomised controlled trials comparing sildenafil citrate with placebo or no treatment for ED in patients with MS. Two review authors independently selected articles for inclusion, extracted data and assessed trial quality. Disagreements were resolved by discussion between review authors. Authors of included studies were contacted for additional information. Results were presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI). Two randomised controlled trials involving a total of 420 patients were identified. Both trials investigated the short-term efficacy and safety of sildenafil citrate for ED in patients with MS. Patients taking sildenafil citrate were more likely to improve their ability to achieve and maintain an erection measured by International Index of Erectile Function and achieve vaginal penetration ( (RR 1.28, 95%CI 0.92 to 1.78) and complete intercourse measured by Sexual Encounter Profile diary (RR RR 1.38, 95%CI 1.00 to 1.90). and receive A global well respond measured by Global Assessment Question (RR 2.72, 95%CI 1.40 to 5.28) was reported. One trial showed sildenafil citrate is effective in quality of life improvement, while the other trial did not find any significant difference between both groups. Both included trials were judged as high risk of attrition bias. Adverse events were also reported: the most common were headache, flushing, rhinitis, visual disturbances and dyspepsia. Two patients suffered serious adverse events: one with coronary artery disease requiring triple bypass surgery and one with a cerebrovascular accident. There is limited evidence to support sildenafil citrate as an effective treatment for ED in patients with MS. Future well designed randomised, double blinded, placebo-controlled trials with long-term duration are needed.

Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies.

PubMed

Thu, Hnin Ei; Mohamed, Isa Naina; Hussain, Zahid; Jayusman, Putri Ayu; Shuid, Ahmad Nazrun

2017-01-01

Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using search terms such as "Eurycoma longifolia", "EL", "Tongkat Ali", "male sexual health", "sexual infertility", "erectile dysfunction", "male libido", and "testosterone levels". Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Cognitive-behavioural suicide prevention for male prisoners: a pilot randomized controlled trial.

PubMed

Pratt, D; Tarrier, N; Dunn, G; Awenat, Y; Shaw, J; Ulph, F; Gooding, P

2015-12-01

Prisoners have an exceptional risk of suicide. Cognitive-behavioural therapy for suicidal behaviour has been shown to offer considerable potential, but has yet to be formally evaluated within prisons. This study investigated the feasibility of delivering and evaluating a novel, manualized cognitive-behavioural suicide prevention (CBSP) therapy for suicidal male prisoners. A pilot randomized controlled trial of CBSP in addition to treatment as usual (CBSP; n = 31) compared with treatment as usual (TAU; n = 31) alone was conducted in a male prison in England. The primary outcome was self-injurious behaviour occurring within the past 6 months. Secondary outcomes were dimensions of suicidal ideation, psychiatric symptomatology, personality dysfunction and psychological determinants of suicide, including depression and hopelessness. The trial was prospectively registered (number ISRCTN59909209). Relative to TAU, participants receiving CBSP therapy achieved a significantly greater reduction in suicidal behaviours with a moderate treatment effect [Cohen's d = -0.72, 95% confidence interval -1.71 to 0.09; baseline mean TAU: 1.39 (S.D. = 3.28) v. CBSP: 1.06 (S.D. = 2.10), 6 months mean TAU: 1.48 (S.D. = 3.23) v. CBSP: 0.58 (S.D. = 1.52)]. Significant improvements were achieved on measures of psychiatric symptomatology and personality dysfunction. Improvements on psychological determinants of suicide were non-significant. More than half of the participants in the CBSP group achieved a clinically significant recovery by the end of therapy, compared with a quarter of the TAU group. The delivery and evaluation of CBSP therapy within a prison is feasible. CBSP therapy offers significant promise in the prevention of prison suicide and an adequately powered randomized controlled trial is warranted.

Strategic value-directed learning and memory in Alzheimer's disease and behavioural-variant frontotemporal dementia.

PubMed

Wong, Stephanie; Irish, Muireann; Savage, Greg; Hodges, John R; Piguet, Olivier; Hornberger, Michael

2018-02-12

In healthy adults, the ability to prioritize learning of highly valued information is supported by executive functions and enhances subsequent memory retrieval for this information. In Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), marked deficits are evident in learning and memory, presenting in the context of executive dysfunction. It is unclear whether these patients show a typical memory bias for higher valued stimuli. We administered a value-directed word-list learning task to AD (n = 10) and bvFTD (n = 21) patients and age-matched healthy controls (n = 22). Each word was assigned a low, medium or high point value, and participants were instructed to maximize the number of points earned across three learning trials. Participants' memory for the words was assessed on a delayed recall trial, followed by a recognition test for the words and corresponding point values. Relative to controls, both patient groups showed poorer overall learning, delayed recall and recognition. Despite these impairments, patients with AD preferentially recalled high-value words on learning trials and showed significant value-directed enhancement of recognition memory for the words and points. Conversely, bvFTD patients did not prioritize recall of high-value words during learning trials, and this reduced selectivity was related to inhibitory dysfunction. Nonetheless, bvFTD patients showed value-directed enhancement of recognition memory for the point values, suggesting a mismatch between memory of high-value information and the ability to apply this in a motivationally salient context. Our findings demonstrate that value-directed enhancement of memory may persist to some degree in patients with dementia, despite pronounced deficits in learning and memory. © 2018 The British Psychological Society.

Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders.

PubMed

McLean, Samantha L; Grayson, Ben; Marsh, Samuel; Zarroug, Samah H O; Harte, Michael K; Neill, Jo C

2016-04-01

Cholinergic dysfunction has been shown to be central to the pathophysiology of Alzheimer's disease and has also been postulated to contribute to cognitive dysfunction observed in various psychiatric disorders, including schizophrenia. Deficits are found across a number of cognitive domains and in spite of several attempts to develop new therapies, these remain an unmet clinical need. In the current study we investigated the efficacy of donepezil, risperidone and selective nicotinic α7 and α4β2 receptor agonists to reverse a delay-induced deficit in recognition memory. Adult female Hooded Lister rats received drug treatments and were tested in the novel object recognition (NOR) task following a 6h inter-trial interval (ITI). In all treatment groups, there was no preference for the left or right identical objects in the acquisition trial. Risperidone failed to enhance recognition memory in this paradigm whereas donepezil was effective such that rats discriminated between the novel and familiar object in the retention trial following a 6h ITI. Although a narrow dose range of PNU-282987 and RJR-2403 was tested, only one dose of each increased recognition memory, the highest dose of PNU-282987 (10mg/kg) and the lowest dose of RJR-2403 (0.1mg/kg), indicative of enhanced cognitive performance. Interestingly, these compounds were also efficacious when administered either before the acquisition or the retention trial of the task, suggesting an important role for nicotinic receptor subtypes in the formation and retrieval of recognition memory. Copyright © 2016. Published by Elsevier B.V.

Reversal of SSRI-induced female sexual dysfunction by adjunctive bupropion in menstruating women: a double-blind, placebo-controlled and randomized study.

PubMed

Safarinejad, Mohammad R

2011-03-01

A significant number of patients undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) report sexual dysfunction. SSRI-induced sexual dysfunction adversely affects quality of life and patient adherence to and compliance with treatment regimens. This trial examined the efficacy and safety of adjunctive bupropion in the treatment of SSRI-induced female sexual dysfunction. Sexual function was assessed by using the sexual function domains of the Female Sexual Function Index (primary efficacy outcome measure) and the Clinical Global Impression Scale adapted for sexual function (secondary efficacy outcome measure). End point treatment satisfaction was assessed using a Visual Analog Scale. A total of 218 women (25-45 years old) with SSRI-induced sexual dysfunction were randomized to receive 12 weeks of double-blind fixed dosed treatment with bupropion sustained release 150 mg b.i.d. (n = 109) or placebo (n = 109). The mean (SD) for Female Sexual Function Index total score was higher in the bupropion sustained release group (25.9 (5.12), 95% confidence interval (CI) 22.2-29.4) than in the placebo group (17.2 (4.9), 95% CI 15.8-20.1) (p = 0.001). Mean (SD) Clinical Global Impression Scale score for the bupropion group (2.4 (0.6), 95% CI 2.0-3.6) was significantly lower than that for the placebo group (4.2 (0.8), 95% CI 3.4-5.4) (p = 0.001). At the end of the trial the mean (SD) scores for desire (4.1 (0.7), 95% CI 3.5-4.8) (p = 0.001), arousal (4.4 (0.6), 95% CI 3.7-4.8) (p = 0.01), lubrication (4.4 (0.4), 95% CI 3.3-4.8) (p = 0.001), orgasm (4.4 (0.5), 95% CI 3.7-4.7) (p = 0.001), and satisfaction (4.2 (0.7), 95% CI 3.4-4.8) (p = 0.001) were significantly higher in the bupropion group. The highest improvement was observed in sexual desire, followed by lubrication. Compared with baseline, desire and lubrication domains increased by 86.4% (95% CI 64.9-102.2%, p = 0.001) and 69.2% (95% CI 44.7-82.6%, p = 0.001) in the bupropion group. Adjunctive treatment with bupropion sustained release during a 12-week period significantly improved key aspects of sexual function in women with SSRI-induced sexual dysfunction.

A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Methods/Design Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include the effect of spironolactone on the change in placebo-corrected maximal oxygen consumption; plasma markers of vascular inflammation and peripheral blood mononuclear cell gene expression profiles; sympathetic nervous system activation, renin-angiotensin-aldosterone system activation and sex hormone metabolism; and right ventricular structure and function using echocardiography and novel high-resolution magnetic resonance imaging-based techniques. Safety and tolerability of spironolactone will be assessed with periodic monitoring for hyperkalemia and renal insufficiency as well as the incidence of drug discontinuation for untoward effects. Trial registration ClinicalTrials.gov: NCT01712620 PMID:23547564

Clinical Predictors of Multiple Organ Dysfunction Syndromes in Pediatric patients with Scrub Typhus.

PubMed

Zhao, Dongying; Zhang, Yongjun; Yin, Zhaoqing; Zhao, Jing; Yang, Defeng; Zhou, Qun

2017-06-01

Scrub typhus can produce multiple organ dysfunction syndrome (MODS). Early recognition of the patients at risk of MODS would be helpful in providing timely management and reducing the mortality. In all, 449 children with scrub typhus were enrolled at three hospitals in Yunnan, China from January 2010 to January 2015. The patients' clinical status of organ system dysfunction was evaluated on the day of discharge from hospital by using standard criteria. The patients were classified into MODS present (64 cases, 14.3%) or MODS absent (385 cases, 85.7%). Multivariate logistic regression analyses revealed that the prognostic factors for MODS included skin rash (odds ratio, OR = 3.3, p = 0.037), time interval form treatment to defervescence (OR = 1.2, p = 0.035), hemoglobin (OR = 0.54, p = 0.041), platelet counts (OR = 0.06, p < 0.001), aspartate-aminotransferase (OR = 4.7, p = 0.011) and total bilirubin (OR = 2.3, p = 0.013). By describing risk factors resulting in MODS in pediatric scrub typhus, our study provides clinicians with important information to improve the clinical monitoring and prognostication of MODS. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Triage of patients with acute gastrointestinal bleeding for intensive care unit admission based on risk factors for poor outcome.

PubMed

Afessa, B

2000-04-01

This study's aim was to determine the prognostic factors and to develop a triage system for intensive care unit (ICU) admission of patients with gastrointestinal bleeding (GIB). This prospective, observational study included 411 adults consecutively hospitalized for GIB. Each patient's selected clinical findings and laboratory values at presentation were obtained. The Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated from the initial findings in the emergency department. Poor outcome was defined as recurrent GIB, emergency surgery, or death. The role of hepatic cirrhosis, APACHE II score, active GIB, end-organ dysfunction, and hypotension in predicting outcome was evaluated. Chi-square, Student's t, Mann-Whitney U, and logistic regression analysis tests were used for statistical comparisons. Poor outcome developed in 81 (20%) patients; 39 died, 23 underwent emergency surgery, and 47 rebled. End-organ dysfunction, active bleeding, hepatic cirrhosis, and high APACHE II scores were independent predictors of poor outcome with odds ratios of 3:1, 3:1, 2:3, and 1:1, respectively. The ICU admission rate was 37%. High APACHE II score, active bleeding, end-organ dysfunction, and hepatic cirrhosis are independent predictors of poor outcome in patients with GIB and can be used in the triage of these patients for ICU admission.

Mitochondrial Dysfunction in Lysosomal Storage Disorders

PubMed Central

de la Mata, Mario; Cotán, David; Villanueva-Paz, Marina; de Lavera, Isabel; Álvarez-Córdoba, Mónica; Luzón-Hidalgo, Raquel; Suárez-Rivero, Juan M.; Tiscornia, Gustavo; Oropesa-Ávila, Manuel

2016-01-01

Lysosomal storage diseases (LSDs) describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS), where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (ΔΨm), diminished ATP production and increased generation of reactive oxygen species (ROS). Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD), the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase). Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs. PMID:28933411

Contemporary role of radiotherapy in the management of penile cancer

PubMed Central

Korzeniowski, Martin Arthur

2017-01-01

Penile cancer is a rare clinical entity that contributes to significant patient morbidity and mortality. Human papilloma virus (HPV) plays an important role in the carcinogenesis of penile squamous cell carcinoma (SCC), is associated with improved clinical outcomes, and is predictive for response to treatment with chemotherapy and radiotherapy. Historically, treatment consisted of radical surgery with partial or total penectomy. While effective for local control, surgical resection can impart significant physical, psychological and sexual dysfunction for afflicted men. Organ preservation strategies offer significant quality of life advantages over standard surgery and can be utilized without compromising oncological control. As an alternative or adjunct to surgical resection, radiation therapy can be used for organ preservation strategies successfully in up to 70% of patients. A variety of treatment techniques can be employed depending on the location and burden of disease. Limited disease can be amenable to treatment with interstitial brachytherapy, surface mold plesiotherapy or external beam radiotherapy. For locally advanced presentations, or for patients not amenable to surgical resection, excellent clinical outcomes can be achieved using a combination of chemotherapy and radiation therapy. Here, we discuss the management of penile SCC using modern radiation therapy treatment techniques, the expected clinical outcomes for organ preservation, as well as the management of side-effects and toxicities. While large randomized trials are being developed, the management of penile cancer is informed from the management of other of other anogenital malignancies, which we also review. PMID:29184783

How does lower urinary tract dysfunction (LUTD) affect sexual function in men and women? ICI-RS 2015-Part 2.

PubMed

Apostolidis, Apostolos; Rantell, Angie; Anding, Ralf; Kirschner-Hermanns, Ruth; Cardozo, Linda

2017-04-01

To discuss available data on the links between LUTD and sexual dysfunction, what is still unknown about the causative effect of disease processes on sexual function (SF), and to suggest proposals for further research. At the 2015 International Consultation on Incontinence-Research Society (ICI-RS), a multi-disciplinary group presented a literature search of what is known about the effect of LUTD on SF in men and women. Wider discussions regarding knowledge gaps, and ideal research methodology ensued and are presented. The underlying mechanisms of the impact of LUTD on SF remain largely unknown. Risk factors for the metabolic syndrome may cause both LUTS and ED in men, and their improvement may improve both conditions. In women, neurovascular changes may be common in LUTD and FSD. Successful LUTS management results in FSD improvement, but the mechanisms are ill understood. Gaps in standardization of sexual dysfunction terminology, variations of assessment, and treatment in clinical practice and research make most studies not comparable. The sensitive knowledge and subjective nature of the problem present challenges and often result in neglecting it. Neurovascular and hormonal factors, but also indirect effects may link LUTD to SD in both sexes, but the evidence is not robust and the mechanisms unclear. There is a need for defining the terminology and standardizing outcomes assessed in clinical trials. The multifactorial nature of SF in both sexes makes trial design challenging and "real world" studies may prove more beneficial for patients' outcomes and clinicians' understanding. © 2017 Wiley Periodicals, Inc.

Electroacupuncture as an adjunctive therapy for motor dysfunction in acute stroke survivors: a systematic review and meta-analyses

PubMed Central

Zhan, Jie; Pan, Ruihuan; Zhou, Mingchao; Tan, Feng; Huang, Zhen; Dong, Jing; Wen, Zehuai

2018-01-01

Objectives To assess the effectiveness and safety of electroacupuncture (EA) combined with rehabilitation therapy (RT) and/or conventional drugs (CD) for improving poststroke motor dysfunction (PSMD). Design Systematic review and meta-analysis. Methods The China National Knowledge Infrastructure, Chinese Biological Medicine Database, Chinese Scientific Journal Database, Cochrane Library, Medline and Embase were electronically searched from inception to December 2016. The methodological quality of the included trials was assessed using the Cochrane risk of bias assessment tool. Statistical analyses were performed by RevMan V.5.3 and Stata SE V.11.0. Results Nineteen trials with 1434 participants were included for qualitative synthesis and meta-analysis. The methodological quality of the included trials was generally poor. The meta-analysis indicated that the EA group might be benefiting more than the non-EA group in terms of the changes in the Fugl-Meyer Assessment Scale (FMA) (weighted mean difference (WMD): 10.79, 95% CI 6.39 to 15.20, P<0.001), FMA for lower extremity (WMD: 5.16, 95% CI 3.78 to 6.54, P<0.001) and activities of daily living (standardised mean difference: 1.37, 95% CI 0.79 to 1.96, P<0.001). However, there was no difference between EA and non-EA groups in terms of the effective rate (relative risk: 1.13, 95% CI 1.00 to 1.27, P=0.050). Moreover, there were not any reports of side effects due to EA combined with RT and/or CD in the included trials. Conclusions This review provides new evidence for the effectiveness and safety of EA combined with RT and/or CD for PSMD. However, the results should be interpreted cautiously because of methodological weakness and publication bias. Further clinical trials with a rigorous design and large sample sizes are warranted. PROSPERO registration number CRD42016037597. PMID:29371267

Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction).

PubMed

Sanz-Ruiz, Ricardo; Casado Plasencia, Ana; Borlado, Luis R; Fernández-Santos, María Eugenia; Al-Daccak, Reem; Claus, Piet; Palacios, Itziar; Sádaba, Rafael; Charron, Dominique; Bogaert, Jan; Mulet, Miguel; Yotti, Raquel; Gilaberte, Immaculada; Bernad, Antonio; Bermejo, Javier; Janssens, Stefan; Fernández-Avilés, Franciso

2017-06-23

Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure. The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction, with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and first-generation stem cells have yielded inconsistent benefits and mixed results. In the search for new and more efficient cellular regenerative products, interesting cardioprotective, immunoregulatory, and cardioregenerative properties have been demonstrated for human cardiac stem cells. On the other hand, allogeneic cells show several advantages over autologous sources: they can be produced in large quantities, easily administered off-the-shelf early after an acute myocardial infarction, comply with stringent criteria for product homogeneity, potency, and quality control, and may exhibit a distinctive immunologic behavior. With a promising preclinical background, CAREMI (Cardiac Stem Cells in Patients With Acute Myocardial Infarction) has been designed as a double-blind, 2:1 randomized, controlled, and multicenter clinical trial that will evaluate the safety, feasibility, and efficacy of intracoronary delivery of allogeneic human cardiac stem cell in 55 patients with large acute myocardial infarction, left ventricular dysfunction, and at high risk of developing heart failure. This phase I/II clinical trial represents a novel experience in humans with allogeneic cardiac stem cell in a rigorously imaging-based selected group of acute myocardial infarction patients, with detailed safety immunologic assessments and magnetic resonance imaging-based efficacy end points. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439398. © 2017 American Heart Association, Inc.

Effects of Low-Intensity Extracorporeal Shockwave Therapy on Erectile Dysfunction: A Systematic Review and Meta-Analysis.

PubMed

Clavijo, Raul I; Kohn, Taylor P; Kohn, Jaden R; Ramasamy, Ranjith

2017-01-01

Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been proposed as an effective non-invasive treatment option for erectile dysfunction (ED). To use systematic review and meta-analysis to assess the efficacy of Li-ESWT by comparing change in erectile function as assessed by the erectile function domain of the International Index of Erectile Function (IIEF-EF) in men undergoing Li-ESWT vs sham therapy for the treatment of ED. Systematic search was conducted of MEDLINE, EMBASE, and ClinicalTrials.gov for randomized controlled trials that were published in peer-reviewed journals or presented in abstract form of Li-ESWT used for the treatment of ED from January 2010 through March 2016. Randomized controlled trials were eligible for inclusion if they were published in the peer-reviewed literature and assessed erectile function outcomes using the IIEF-EF score. Estimates were pooled using random-effects meta-analysis. Change in IIEF-EF score after treatment with Li-ESWT in patients treated with active treatment vs sham Li-ESWT probes. Data were extracted from seven trials involving 602 participants. The average age was 60.7 years and the average follow-up was 19.8 weeks. There was a statistically significant improvement in pooled change in IIEF-EF score from baseline to follow-up in men undergoing Li-ESWT vs those undergoing sham therapy (6.40 points; 95% CI = 1.78-11.02; I 2  = 98.7%; P < .0001 vs 1.65 points; 95% CI = 0.92-2.39; I 2  = 64.6%; P < .0001; between-group difference, P = .047). Significant between-group differences were found for total treatment shocks received by patients (P < .0001). In this meta-analysis of seven randomized controlled trials, treatment of ED with Li-ESWT resulted in a significant increase in IIEF-EF scores. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction.

PubMed

Murphy, Laura S; Wickersham, Nancy; McNeil, J Brennan; Shaver, Ciara M; May, Addison K; Bastarache, Julie A; Ware, Lorraine B

2017-10-06

Disruption of the endothelial glycocalyx contributes to acute lung injury in experimental sepsis but has not been well studied in humans. To study glycocalyx degradation in sepsis-induced ARDS, we measured plasma levels of syndecan-1, a marker for glycocalyx degradation. The present study is a retrospective observational study of 262 ventilated medical ICU patients at risk of ARDS due to severe sepsis and APACHE II ≥ 25. Plasma syndecan-1 was measured at study enrollment. Primary analysis focused on the association between syndecan-1 levels and the development of ARDS, other organ dysfunction (Brussels criteria), or in-hospital mortality. Overall, 135 (52%) patients developed ARDS. In patients with non-pulmonary sepsis, syndecan-1 levels were associated with ARDS (p = 0.05). Regardless of etiology of sepsis, higher syndecan-1 levels were associated with hepatic (p < 0.001), renal (p = 0.003), coagulation (p = 0.001), and circulatory (p = 0.02) failure as well as in-hospital mortality (p = 0.001), and there was a significant association between syndecan-1 levels and the number of vasopressors required in the first 24 h (p < 0.001). In addition, elevated syndecan levels were independently predictive of mortality in multivariable logistic regression adjusted for age and APACHE II score (odds ratio 1.85 per log increase in syndecan-1, 95% CI 1.056-3.241, p = 0.03). The extent of endothelial glycocalyx degradation is associated with non-pulmonary organ dysfunction in subjects with sepsis and is associated with ARDS but only in the subgroup with non-pulmonary sepsis. Measurement of syndecan-1 levels in sepsis patients might be useful for identifying patients at high risk of organ dysfunction and mortality as well as those who could benefit from therapies targeted at protecting or restoring the glycocalyx.

High-volume plasma exchange in a patient with acute liver failure due to non-exertional heat stroke in a sauna.

PubMed

Chen, Kuan-Jung; Chen, Tso-Hsiao; Sue, Yuh-Mou; Chen, Tzay-Jinn; Cheng, Chung-Yi

2014-10-01

Heat stroke is a life-threatening condition characterized by an increased core body temperature (over 40°C) and a systemic inflammatory response, which may lead to a syndrome of multiple organ dysfunction. Heat stroke may be due to either strenuous exercise or non-exercise-induced exposure to a high environmental temperature. Current management of heat stroke is mostly supportive, with an emphasis on cooling the core body temperature and preventing the development of multiple organ dysfunction. Prognosis of heat stroke depends on the severity of organ involvement. Here, we report a rare case of non-exercise-induced heat stroke in a 73-year-old male patient who was suffering from acute liver failure after prolonged exposure in a hot sauna room. We successfully managed this patient by administering high-volume plasma exchange, and the patient recovered completely after treatment. © 2014 Wiley Periodicals, Inc.

The Role of Pay Satisfaction in Instructor Satisfaction

ERIC Educational Resources Information Center

Wilson, Jackson

2009-01-01

Voluntary employee turnover is a major factor affecting adventure education (AE) organizations (Garret, 2003). Voluntary turnover often is dysfunctional for both employees and organizations (Birmingham, 1989; Podsakoff, LePine, & LePine, 2007). Turnover can result in increased employee and organizational costs (e.g., McKinney, Bartlett, &…

D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

PubMed

Angstwurm, Matthias W A; Reininger, Armin J; Spannagl, Michael

2004-01-01

The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

Extracorporeal Life Support Bridge to Ventricular Assist Device: The Double Bridge Strategy.

PubMed

Marasco, Silvana F; Lo, Casey; Murphy, Deirdre; Summerhayes, Robyn; Quayle, Margaret; Zimmet, Adam; Bailey, Michael

2016-01-01

In patients requiring left ventricular assist device (LVAD) support, it can be difficult to ascertain suitability for long-term mechanical support with LVAD and eventual transplantation. LVAD implantation in a shocked patient is associated with increased morbidity and mortality. Interest is growing in the utilization of extracorporeal life support (ECLS) as a bridge-to-bridge support for these critically unwell patients. Here, we reviewed our experience with ECLS double bridging. We hypothesized that ECLS double bridging would stabilize end-organ dysfunction and reduce ventricular assist device (VAD) implant perioperative mortality. We conducted a retrospective review of prospectively collected data for 58 consecutive patients implanted with a continuous-flow LVAD between January 2010 and December 2013 at The Alfred Hospital, Melbourne, Victoria, Australia. Twenty-three patients required ECLS support pre-LVAD while 35 patients underwent LVAD implantation without an ECLS bridge. Preoperative morbidity in the ECLS bridge group was reflected by increased postoperative intensive care duration, blood loss, blood product use, and postoperative renal failure, but without negative impact upon survival when compared with the no ECLS group. ECLS stabilization improved end-organ function pre-VAD implant with significant improvements in hepatic and renal dysfunction. This series demonstrates that the use of ECLS bridge to VAD stabilizes end-organ dysfunction and reduces VAD implant perioperative mortality from that traditionally reported in these "crash and burn" patients. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Design and rationale of Heart and Lung Failure – Pediatric INsulin Titration Trial (HALF-PINT): A randomized clinical trial of tight glycemic control in hyperglycemic critically ill children☆

PubMed Central

Agus, Michael SD; Hirshberg, Ellie; Srinivasan, Vijay; Faustino, Edward Vincent; Luckett, Peter M; Curley, Martha AQ; Alexander, Jamin; Asaro, Lisa A; Coughlin-Wells, Kerry; Duva, Donna; French, Jaclyn; Hasbani, Natalie; Sisko, Martha T; Soto-Rivera, Carmen L; Steil, Garry; Wypij, David; Nadkarni, Vinay M

2017-01-01

Objectives Test whether hyperglycemic critically ill children with cardiovascular and/or respiratory failure experience more ICU-free days when assigned to tight glycemic control with a normoglycemic versus hyperglycemic blood glucose target range. Design Multi-center randomized clinical trial. Setting Pediatric ICUs at 35 academic hospitals. Patients Children aged 2 weeks to 17 years receiving inotropic support and/or acute mechanical ventilation, excluding cardiac surgical patients. Interventions Patients receive intravenous insulin titrated to either 80–110 mg/dL (4.4–6.1 mmol/L) or 150–180 mg/dL (8.3–10.0 mmol/L). The intervention begins upon confirmed hyperglycemia and ends when the patient meets study-defined ICU discharge criteria or after 28 days. Continuous glucose monitoring, a minimum glucose infusion, and an explicit insulin infusion algorithm are deployed to achieve the BG targets while minimizing hypoglycemia risk. Measurements and main results The primary outcome is ICU-free days (equivalent to 28-day hospital mortality-adjusted ICU length of stay). Secondary outcomes include 90-day hospital mortality, organ dysfunction scores, ventilator-free days, nosocomial infection rate, neurodevelopmental outcomes, and nursing workload. To detect an increase of 1.25 ICU-free days (corresponding to a 20% relative reduction in 28-day hospital mortality and a one-day reduction in ICU length of stay), 1414 patients are needed for 80% power using a two-sided 0.05 level test. Conclusions This trial tests whether hyperglycemic critically ill children randomized to 80–110 mg/dL benefit more than those randomized to 150–180 mg/dL. This study implements validated bedside support tools including continuous glucose monitoring and a computerized algorithm to enhance patient safety and ensure reproducible bedside decision-making in achieving glycemic control. PMID:28042054

The impact of extracerebral organ failure on outcome of patients after cardiac arrest: an observational study from the ICON database.

PubMed

Nobile, Leda; Taccone, Fabio S; Szakmany, Tamas; Sakr, Yasser; Jakob, Stephan M; Pellis, Tommaso; Antonelli, Massimo; Leone, Marc; Wittebole, Xavier; Pickkers, Peter; Vincent, Jean-Louis

2016-11-14

We used data from a large international database to assess the incidence and impact of extracerebral organ dysfunction on prognosis of patients admitted after cardiac arrest (CA). This was a sub-analysis of the Intensive Care Over Nations (ICON) database, which contains data from all adult patients admitted to one of 730 participating intensive care units (ICUs) in 84 countries from 8-18 May 2012, except admissions for routine postoperative surveillance. For this analysis, patients admitted after CA (defined as those with "post-anoxic coma" or "cardiac arrest" as the reason for ICU admission) were included. Data were collected daily in the ICU for a maximum of 28 days; patients were followed up for outcome data until death, hospital discharge, or a maximum of 60 days in-hospital. Favorable neurological outcome was defined as alive at hospital discharge with a last available neurological Sequential Organ Failure Assessment (SOFA) subscore of 0-2. Among the 469 patients admitted after CA, 250 (53 %) had had out-of-hospital CA; 210 (45 %) patients died in the ICU and 357 (76 %) had an unfavorable neurological outcome. Non-survivors had a higher incidence of renal (43 vs. 16 %), cardiovascular (56 vs. 45 %), and respiratory (62 vs. 48 %) failure on admission and during the ICU stay than survivors (all p < 0.05). Similar results were found for patients with unfavorable vs. favorable neurological outcomes. In multivariable analysis, independent predictors of ICU mortality were renal failure on admission, high admission Simplified Acute Physiology Score (SAPS) II, high maximum serum lactate levels within the first 24 h after ICU admission, and development of sepsis. Independent predictors of unfavorable neurological outcome were mechanical ventilation on admission, high admission SAPS II score, and neurological dysfunction on admission. In this multicenter cohort, extracerebral organ dysfunction was common in CA patients. Renal failure on admission was the only extracerebral organ dysfunction independently associated with higher ICU mortality.

4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study.

PubMed

Madách, Krisztina; Aladzsity, István; Szilágyi, Agnes; Fust, George; Gál, János; Pénzes, István; Prohászka, Zoltán

2010-01-01

Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer (p = 0.091), fewer ventilation-free days (p = 0.008) and days without septic shock (p = 0.095) were observed during the first 28 days. In Caucasian patients with severe sepsis due to pneumonia carriers of the 4G allele of PAI-1 polymorphism have higher risk for multiple organ dysfunction syndrome and septic shock and in agreement they showed more fulminant disease progression based on continuous clinical variables.

Effect of mandibular mobilization on electromyographic signals in muscles of mastication and static balance in individuals with temporomandibular disorder: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background The stomatognathic system and dysfunction in this system may be related to postural control. The proposal of the present study is to assess the effect of mandibular mobilization in individuals with temporomandibular disorder using surface electromyography of the muscles of mastication and stabilometric variables. Methods/Design A randomized, controlled, blind, clinical trial will be carried out, with the participants divided into three groups: 1) facial massage therapy (control group), 2) nonspecific mandibular mobilization and 3) specific mandibular mobilization. All groups will be assessed before and after treatment using the Research Diagnostic Criteria for Temporomandibular Disorders, surface electromyography of the masseter and temporal muscles and stabilometry. This study is registered with the Brazilian Registry of Clinical Trials (RBR9x8ssz). Discussion A large number of studies have employed surface electromyography to investigate the function/dysfunction of the muscles of mastication and associations with signs and symptoms of temporomandibular disorders. However, it has not yet been determined whether stabilometric variables offer adequate reliability in patients with this disorder. The results of the proposed study will help determine whether specific and/or nonspecific mandibular mobilization exerts an effect on the muscles of mastication and postural control. Moreover, if an effect is detected, the methodology defined in the proposed study will allow identifying whether the effect is local (found only in the muscles of mastication), global (found only in postural control) or generalized. PMID:24083628

Report from a consensus conference on antibody-mediated rejection in heart transplantation

PubMed Central

Kobashigawa, Jon; Crespo-Leiro, Maria G.; Ensminger, Stephan M.; Reichenspurner, Hermann; Angelini, Annalisa; Berry, Gerald; Burke, Margaret; Czer, Lawrence; Hiemann, Nicola; Kfoury, Abdallah G.; Mancini, Donna; Mohacsi, Paul; Patel, Jignesh; Pereira, Naveen; Platt, Jeffrey L.; Reed, Elaine F.; Reinsmoen, Nancy; Rodriguez, E. Rene; Rose, Marlene L.; Russell, Stuart D.; Starling, Randy; Suciu-Foca, Nicole; Tallaj, Jose; Taylor, David O.; Van Bakel, Adrian; West, Lori; Zeevi, Adriana; Zuckermann, Andreas

2012-01-01

BACKGROUND The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation. METHODS The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus. RESULTS A tentative pathology diagnosis of AMR was established, however, the pathologist felt that further discussion was needed prior to a formal recommendation for AMR diagnosis. One of the most important outcomes of this conference was that a clinical definition for AMR (cardiac dysfunction and/or circulating donor-specific antibody) was no longer believed to be required due to recent publications demonstrating that asymptomatic (no cardiac dysfunction) biopsy-proven AMR is associated with subsequent greater mortality and greater development of cardiac allograft vasculopathy. It was also noted that donor-specific antibody is not always detected during AMR episodes as the antibody may be adhered to the donor heart. Finally, recommendations were made for the timing for specific staining of endomyocardial biopsy specimens and the frequency by which circulating antibodies should be assessed. Recommendations for management and future clinical trials were also provided. CONCLUSIONS The AMR Consensus Conference brought together clinicians, pathologists and immunologists to further the understanding of AMR. Progress was made toward a pathology AMR grading scale and consensus was accomplished regarding several clinical issues. PMID:21300295

Dysfunctional Attitudes Scale Perfectionism: A Predictor and Partial Mediator of Acute Treatment Outcome among Clinically Depressed Adolescents

ERIC Educational Resources Information Center

Jacobs, Rachel H.; Silva, Susan G.; Reinecke, Mark A.; Curry, John F.; Ginsburg, Golda S.; Kratochvil, Christopher J.; March, John S.

2009-01-01

The effect of perfectionism on acute treatment outcomes was explored in a randomized controlled trial of 439 clinically depressed adolescents (12-17 years of age) enrolled in the Treatment for Adolescents with Depression Study (TADS) who received cognitive behavior therapy (CBT), fluoxetine, a combination of CBT and FLX, or pill placebo. Measures…

Iron overload in myelodysplastic syndromes (MDS).

PubMed

Gattermann, Norbert

2018-01-01

Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

Prospective, randomized comparison between raloxifene and clomiphene citrate for ovulation induction in polycystic ovary syndrome.

PubMed

de Paula Guedes Neto, Ernesto; Savaris, Ricardo Francalacci; von Eye Corleta, Helena; de Moraes, Gisele Silva; do Amaral Cristovam, Rafael; Lessey, Bruce A

2011-09-01

To compare the ovulation rate between raloxifene and clomiphene citrate (CC) in patients with polycystic ovary syndrome (PCOS). Double-blind, randomized, superiority clinical trial. Tertiary university hospital. Women with ovulatory dysfunction and PCOS based on the Rotterdam criteria. One of two oral treatments: 5 days of 100 mg/day of CC or R. Ovulation, based on follicle collapse on serial ultrasound and midsecretory serum progesterone concentration (≥3 ng/dL). The women with PCOS (n = 82) were randomized to receive CC (n = 40) or raloxifene (n = 42). From these, 68 patients finished the trial according to the protocol (CC: n = 37; raloxifene: n = 31). There were no statistically significant differences between the groups in ovulation rates per an intention-to-treat analysis based on ultrasound alone (CC: 21 of 40 vs. raloxifene: 17 of 42) or on progesterone levels (CC: 16 of 40 vs. raloxifene: 11 of 42). No serious adverse events were observed in either group. No statistically significant difference in ovulation was observed between raloxifene and clomiphene citrate in patients with PCOS with ovulatory dysfunction. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.