Total Number Of Adverse Events Research Articles

Efficacy of Adaptogenic Supplements on Adapting to Stress: A Randomized, Controlled Trial

Efficacy of Adaptogenic Supplements on Adapting to Stress: A Randomized, Controlled Trial Objective: The aim of this randomized, double-blinded, placebocontrolled trial was to assess the efficacy of adaptogens on the physical and emotional stress-induced loss of concentration, coordination, fatigue and hormonal changes in 215 elite athletes. This study explores two formulations, ADAPT-232S and ADAPT-S, that had standardized contents of salidroside, schisandrin, eleutherosides B and E, ecdisterone and pantothenic acid. Methods: Standard psychological scales and computerized neurophysiological and blood tests were used to assess the efficacy of the treatments at the baseline and then after 7, 8, 28 and 29 days of daily oral administration. Fatigue was chosen as one of the primary outcomes and was measured as selective inattention and impulsivity in the Conners’ computerized continuous performance test (CCPT) and three standard psychological rating scales, the fatigue severity score (FSS), the perceived stress score (PSS) and the Shirom-Melamed burnout score (SMBS). The anabolic index (blood testosterone/cortisol ratio) and blood lactate were selected as primary outcomes in the phase of recovery of athletes on the second day after heavy physical exercise or competitions. Results: Significant differences (p<0.01) between the placebo and verum groups in favor of ADAPT-232S and ADAPT-S were found in the primary and some secondary outcomes: Conners’ computerized continuous performance test parameters of selective attention and impulsivity, anabolic index, cortisol and lactate levels in blood, fatigue severity score, perceived stress score, and physical performance tests. The sport achievements of athletes were in favor of the ADAPT groups. All of the treatments were well tolerated. The total numbers of adverse events did not differ among the three groups. Conclusions: The adaptogenic preparations, ADAPT-232S or ADAPT-S, are safe and effective supplements for enhancing tolerance to physical and emotional stress as well as for the recovery of athletes during and after high–intensity exercise and competitions.

Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial

Elevated plasma homocysteine concentrations are a risk factor for osteoporotic fractures. Lowering homocysteine with combined vitamin B-12 and folic acid supplementation may reduce fracture risk. This study [B-vitamins for the PRevention Of Osteoporotic Fractures (B-PROOF)] aimed to determine whether vitamin B-12 and folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly individuals. This was a double-blind, randomized, placebo-controlled trial in 2919 participants aged ≥65 y with elevated homocysteine concentrations (12-50 μmol/L). Participants were assigned to receive daily 500 μg vitamin B-12 plus 400 μg folic acid or placebo supplementation for 2 y. Both intervention and placebo tablets also contained 600 IU vitamin D3. The primary endpoint was time to first osteoporotic fracture. Exploratory prespecified subgroup analyses were performed in men and women and in individuals younger than and older than age 80 y. Data were analyzed according to intention-to-treat and per-protocol principles. Osteoporotic fractures occurred in 61 persons (4.2%) in the intervention group and 75 persons (5.1%) in the placebo group. Osteoporotic fracture risk was not significantly different between groups in the intention-to-treat analyses (HR: 0.84; 95% CI: 0.58, 1.21) or per-protocol analyses (HR: 0.81; 95% CI: 0.54, 1.21). For persons aged >80 y, in per-protocol analyses, osteoporotic fracture risk was lower in the intervention group than in the placebo group (HR: 0.27; 95% CI: 0.10, 0.74). The total number of adverse events (including mortality) did not differ between groups. However, 63 and 42 participants in the intervention and placebo groups, respectively, reported incident cancer (HR: 1.56; 95% CI: 1.04, 2.31). These data show that combined vitamin B-12 and folic acid supplementation had no effect on osteoporotic fracture incidence in this elderly population. Exploratory subgroup analyses suggest a beneficial effect on osteoporotic fracture prevention in compliant persons aged >80 y. However, treatment was also associated with increased incidence of cancer, although the study was not designed for assessing cancer outcomes. Therefore, vitamin B-12 plus folic acid supplementation cannot be recommended at present for fracture prevention in elderly people. The B-PROOF study was registered with the Netherlands Trial Register (trialregister.nl) as NTR1333 and at clinicaltrials.gov as NCT00696414.

Adverse Events after Unruptured Cerebral Aneurysm Treatment: A Single-center Experience with Clipping/Coil Embolization Combined Units

Indications of clipping (Clip) or coil embolization (Coil) for unruptured cerebral aneurysms (uAN) was not elaborated because prediction of rupture and risk of treatment are difficult. This study aims to determine the risk-benefit analysis of treating uAN by a comprehensive and retrospective investigation of the adverse events and sequelae in patients treated by our Clip/Coil combined units. Clip and Coil were performed in 141 and 80 patients, respectively; Clip for middle cerebral artery AN and Coil for paraclinoid or basilar apex AN. Worsening of modified Rankin scale or mini-mental state examination was defined as major morbidity. Minor morbidity or transient morbidity was defined as other neurologic deficits. Mortality and these morbidities were considered as serious adverse events. Convulsion or events outside the brain were defined as mild adverse events. Total mortality and major morbidity were low. Incidence of serious adverse events was not significantly different between the Clip and Coil (17 patients [12.1%] and 6 patients [7.5%]), but the number of total adverse events was significantly different (32 patients [22.7%] in Clip vs. 8 patients [10.0%] in Coil). Because mild morbidities were significantly more frequent in the Clip (20 patients [14.2%]) compared with the Coil (2 patients [2.5%]). Convulsion occurred in 11 (7.8%) patients in the Clip but none in the Coil. Our combined unit decreased the occurrence of mortality/major morbidity; however, minor adverse effects were common, especially in the Clip group because of many intrinsic problems of Clip itself. This result suggests further consideration for the treatment modality for uAN.

Rhodiola rosea for mental and physical fatigue in nursing students: a randomized controlled trial.

BackgroundFatigue is one of many unintended consequences of shift work in the nursing profession. Natural health products (NHPs) for fatigue are becoming an increasingly popular topic of clinical study; one such NHP is Rhodiola rosea. A well-designed, rigorously conducted randomized controlled trial is required before therapeutic claims for this product can be made.ObjectiveTo compare the efficacy of R. rosea with placebo for reducing fatigue in nursing students on shift work.DesignA parallel-group randomized, double-blinded, placebo-controlled trial of 18–55 year old students from the Faculty of Nursing from the University of Alberta, participating in clinical rotations between January 2011 and September 2011.InterventionsParticipants were randomized to take 364 mg of either R. rosea or identical placebo at the start of their wakeful period and up to one additional capsule within the following four hours on a daily basis over a 42-day period.OutcomesThe primary outcome was reduction in fatigue over the 42-day trial period measured using the Vitality-subscale of the RAND-36, cross-validated by the visual analogue scale for fatigue (VAS-F). Secondary outcomes included health-related quality of life, individualized outcomes assessment, and adverse events.ResultsA total of 48 participants were randomized to R. rosea (n = 24) or placebo (n = 24). The mean change in scores on the Vitality-subscale was significantly different between the study groups at day 42 in favor of placebo (−17.3 (95% CI −30.6, −3.9), p = 0.011), The mean change in scores on the VAS-F was also significantly difference between study groups at day 42 in favour of placebo (1.9 (95% CI 0.4, 3.5), p = 0.015). Total number of adverse events did not differ between R. rosea and placebo groups.ConclusionThis study indicates that among nursing students on shift work, a 42-day course of R. Rosea compared with placebo worsened fatigue; however, the results should be interpreted with caution.Trial Registration Clinicaltrials.gov NCT01278992

Investigating the relationship between adverse events and infrastructure development in an active war theater using soft computing techniques

The purpose of this paper is to investigate the relationship between adverse events and infrastructure development investments in an active war theater by using soft computing techniques including fuzzy inference systems (FIS), artificial neural networks (ANNs), and adaptive neuro-fuzzy inference systems (ANFIS) where the accuracy of the predictions is directly beneficial from an economic and humanistic point of view. Fourteen developmental and economic improvement projects were selected as independent variables. A total of four outputs reflecting the adverse events in terms of the number of people killed, wounded or hijacked, and the total number of adverse events has been estimated.The results obtained from analysis and testing demonstrate that ANN, FIS, and ANFIS are useful modeling techniques for predicting the number of adverse events based on historical development or economic project data. When the model accuracy was calculated based on the mean absolute percentage error (MAPE) for each of the models, ANN had better predictive accuracy than FIS and ANFIS models, as demonstrated by experimental results. For the purpose of allocating resources and developing regions, the results can be summarized by examining the relationship between adverse events and infrastructure development in an active war theater, with emphasis on predicting the occurrence of events. We conclude that the importance of infrastructure development projects varied based on the specific regions and time period.

Non-steroidal anti-inflammatory drugs for acute gout.

Non-steroidal anti-inflammatory drugs for acute gout.

Using a hybrid electronic medical record system for the surveillance of adverse surgical events and human error in a developing world surgical service.

The quantification and analysis of adverse events is essential to benchmark surgical outcomes and establish a foundation for quality improvement interventions. We developed a hybrid electronic medical record (HEMR) system for the accurate collection and integration of data into a structured morbidity and mortality (M&M) meeting. The HEMR system was implemented on January 1, 2013. It included a mechanism to capture and classify adverse events using the ICD-10 coding system. This was achieved by both prospective reporting by clients and by retrospective sentinel-event-trawling performed by administrators. From January 1, 2013 to March 20, 2014, 6,217 patients were admitted within the tertiary surgical service of Greys Hospital. A total of 1,314 (21.1 %) adverse events and 315 (5.1 %) deaths were recorded. The adverse events were divided into 875 "pathology-related" morbidities and 439 "error-related" morbidities. Pathology-related morbidities included 725 systemic complications and 150 operative complications. Error-related morbidities included 257 cognitive errors, 158 (2.5 %) iatrogenic injuries, and 24 (1.3 %) missed injuries. Error accounted for 439 (33 %) of the total number of adverse events. A total of 938 (71.4 %) adverse events were captured prospectively, whereas the remaining 376 (28.6 %) were captured retrospectively. The ICD-10 coding system was found to have some limitations in its classification of adverse events. The HEMR system has provided the necessary platform within our service to benchmark the incidence of adverse events. The use of the international ICD-10 coding system has identified some limitations in its ability to classify and categorise adverse events in surgery.

Colchicine for acute gout.

Colchicine for acute gout.

Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients.

Genital herpes is caused by herpes simplex virus 1 (HSV-1) or 2 (HSV-2). Some infected people experience outbreaks of genital herpes, typically, characterized by vesicular and erosive localized painful genital lesions. To compare the effectiveness and safety of three oral antiviral drugs (acyclovir, famciclovir and valacyclovir) prescribed to suppress genital herpes outbreaks in non-pregnant patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the search portal of the World Health Organization International Clinical Trials Registry Platform and pharmaceutical company databases up to February 2014. We also searched US Food and Drug Administration databases and proceedings of seven congresses to a maximum of 10 years. We contacted trial authors and pharmaceutical companies. We selected parallel-group and cross-over randomized controlled trials including patients with recurrent genital herpes caused by HSV, whatever the type (HSV-1, HSV-2, or undetermined), with at least four recurrences per year (trials concerning human immunodeficiency virus (HIV)-positive patients or pregnant women were not eligible) and comparing suppressive oral antiviral treatment with oral acyclovir, famciclovir, and valacyclovir versus placebo or another suppressive oral antiviral treatment. Two review authors independently selected eligible trials and extracted data. The Risk of bias tool was used to assess risk of bias. Treatment effect was measured by the risk ratio (RR) of having at least one genital herpes recurrence. Pooled RRs were derived by conventional pairwise meta-analyses. A network meta-analysis allowed for estimation of all possible two-by-two comparisons between antiviral drugs. A total of 26 trials (among which six had a cross-over design) were included. Among the 6950 randomly assigned participants, 54% (range 0 to 100%) were female, mean age was 35 years (range 26 to 45.1), and the mean number of recurrences per year was 11 (range 6.3 to 17.8). Duration of treatment was two to 12 months. Risk of bias was considered high for half of the studies and unclear for the other half. A total of 14 trials compared acyclovir versus placebo, four trials compared valacyclovir versus placebo and 2 trials compared valacyclovir versus no treatment. Three trials compared famciclovir versus placebo. Two trials compared valacyclovir versus famciclovir and one trial compared acyclovir versus valacyclovir versus placebo.We analyzed data from 22 trials for the outcome: risk of having at least one clinical recurrence. We could not obtain the outcome data for four trials. In placebo-controlled trials, there was a low quality evidence that the risk of having at least one clinical recurrence was reduced with acyclovir (nine parallel-group trials, n = 2049; pooled RR 0.48, 95% confidence interval (CI) 0.39 to 0.58), valacyclovir (four trials, n = 1788; pooled RR 0.41, 95% CI 0.24 to 0.69), or famciclovir (two trials, n = 732; pooled RR 0.57, 95% CI 0.50 to 0.64). The six cross-over trials showed larger treatment effects on average than the parallel-group trials. We found evidence of a small-study effect for acyclovir placebo-controlled trials (adjusted pooled RR 0.61, 95% CI 0.49 to 0.75). In analyzing parallel-group trials by daily dose, no clear evidence was found of a dose-response relationship for any drug. In head-to-head trials, the risk of having at least one recurrence was increased with valacyclovir rather than acyclovir (one trial, n = 1345; RR 1.16, 95% CI 1.01 to 1.34) and was not significantly different from that seen with famciclovir as compared with valacyclovir (one trial, n = 320; RR 1.18, 95% CI 0.86 to 1.63).We included 16 parallel-arm trials in a network meta-analysis and we were unable to determine which of the drugs was most effective in reducing the risk of at least one clinical recurrence (after adjustment for small-study effects, pooled RR 0.83, 95% CI 0.61 to 1.11 for valacyclovir vs acyclovir; pooled RR 1.04, 95% CI, 0.71 to 1.49 for famciclovir vs acyclovir; and pooled RR 1.26, 95% CI 0.89 to 1.75 for famciclovir vs valacyclovir). Safety data were sought but were reported as total numbers of adverse events. Owing to risk of bias and inconsistency, there is low quality evidence that suppressive antiviral therapy with acyclovir, valacyclovir or famciclovir in pacients experiencing at least four recurrences of genital herpes per year decreases the number of pacients with at least one recurrence as compared with placebo. Network meta-analysis of the few direct comparisons and the indirect comparisons did not show superiority of one drug over another.

Supervision and responses of psychiatry residents to adverse patient events.

Throughout training, psychiatry residents may experience adverse patient outcomes. The purpose of this study was to explore whether residents' perceptions of the quality of their supervision impacts their emotional reactions to adverse events. All psychiatry residents from a training program at an academic medical center who were in their PGY2-4 years, as well as those in their first year out of training, were recruited to participate. Those who self-identified as having experienced an adverse event participated in a semi-structured interview. For the purpose of the study, "adverse event" was defined as follows: patient suicide, patient homicide or homicide attempt outside the hospital, patient violence inside the hospital, life-threatening reaction to psychotropic medication, and physical assault of a resident by a patient. In this sample, 22 of the 64 residents (34 %) reported experiencing an adverse event. Of these, 21/22 (95 %) participated in the interview. Two residents reported experiencing two adverse events; the total number of adverse events analyzed was 23. For 21/23 (91 %) of these events, respondents felt that the quality of the supervision they received impacted their emotional reactions to the event. The supervisory relationship appears to play a significant role in how residents experience, and potentially learn from, adverse events; this has practical implications for educators and leaders.

Application of nursing inspection log on nursing quality control

Objective To study the role of nursing inspection log in the management of nursing quality control.Methods Totals of 10 wards of internal medicine were randomized into the intervention group (5 wards) and the control group (5 wards).From January 2012,nursing inspections log was used in the intervention group,combined with the rounds of the wards to inspect the daily work.The existed problem of last week was reviewed every week.Specified nurse was responsible for the quality control and recorded when the head nurse was off the shift.The head nurse checked the results of quality control regularly.The incidence of adverse events and quality control results were compared between groups.Results In the intervention group,the times of adverse events of completion of core system,nursing quality of hospital admission and discharge,nursing quality of severe patients,quality of nursing document,quality of disinfection and isolation and quality of wards' management were 26,28,25,15,10 and 14,which were less than 52,48,40,30,23 and 28 in the control group.The differences were significant (x2 =11.93,7.45,4.87,6.32,6.17,5.86,respectively; P ＜ 0.05).The control group discharged 6 259 patients,and the intervention group discharged 6 347 patients.The total number of adverse events was 32 patients in the intervention group (0.50％) and 73 patients in the control group (1.17％).The difference was significant (x2 =16.73,P ＜ 0.05).Conclusions The inspection log can improve nursing quality control and decrease adverse events. Key words: Nursing; Inspection log; Quality control; Adverse events

Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial

<h2>Summary</h2><h3>Background</h3> Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in patients with the disease, and calorie-dense diets increased survival in a mouse model. We aimed to assess the safety and tolerability of two hypercaloric diets in patients with amyotrophic lateral sclerosis receiving enteral nutrition. <h3>Methods</h3> In this double-blind, placebo-controlled, randomised phase 2 clinical trial, we enrolled adults with amyotrophic lateral sclerosis from participating centres in the USA. Eligible participants were aged 18 years or older with no history of diabetes or liver or cardiovascular disease, and who were already receiving percutaneous enteral nutrition. We randomly assigned participants (1:1:1) using a computer-generated list of random numbers to one of three dietary interventions: replacement calories using an isocaloric tube-fed diet (control), a high-carbohydrate hypercaloric tube-fed diet (HC/HC), or a high-fat hypercaloric tube-fed diet (HF/HC). Participants received the intervention diets for 4 months and were followed up for 5 months. The primary outcomes were safety and tolerability, analysed in all patients who began their study diet. This trial is registered with ClinicalTrials.gov, number NCT00983983. <h3>Findings</h3> Between Dec 14, 2009, and Nov 2, 2012, we enrolled 24 participants, of whom 20 started their study diet (six in the control group, eight in the HC/HC group, and six in the HF/HC group). One patient in the control group, one in the HC/HC group, and two in the HF/HC group withdrew consent before receiving the intervention. Participants who received the HC/HC diet had a smaller total number of adverse events than did those in the other groups (23 in the HC/HC group <i>vs</i> 42 in the control group <i>vs</i> 48 in the HF/HC group; overall, p=0·06; HC/HC <i>vs</i> control, p=0·06) and significantly fewer serious adverse events than did those on the control diet (none <i>vs</i> nine; p=0·0005). Fewer patients in the HC/HC group discontinued their study diet due to adverse events (none [0%] of eight in the HC/HC group <i>vs</i> three [50%] of six in the control group). During the 5 month follow-up, no deaths occurred in the nine patients assigned to the HC/HC diet compared with three deaths (43%) in the seven patients assigned to the control diet (log-rank p=0·03). Adverse events, tolerability, deaths, and disease progression did not differ significantly between the HF/HC group and the control group. <h3>Interpretation</h3> Our results provide preliminary evidence that hypercaloric enteral nutrition is safe and tolerable in patients with amyotrophic lateral sclerosis, and support the study of nutritional interventions in larger randomised controlled trials at earlier stages of the disease. <h3>Funding</h3> Muscular Dystrophy Association, National Center for Research Resources, National Institutes of Health, and Harvard NeuroDiscovery Center.

Tamponade in surgery for retinal detachment associated with proliferative vitreoretinopathy

Retinal detachment (RD) with proliferative vitreoretinopathy (PVR) often requires surgery to restore normal anatomy and to stabilize or improve vision. PVR usually occurs in association with recurrent RD (that is, after initial retinal re-attachment surgery) but occasionally may be associated with primary RD. Either way, a tamponade agent (gas or silicone oil) is needed during surgery to reduce the rate of postoperative recurrent RD. The objective of this review was to assess the relative safety and effectiveness of various tamponade agents used with surgery for retinal detachment (RD) complicated by proliferative vitreoretinopathy (PVR). We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2013), EMBASE (January 1980 to June 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to June 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 26 June 2013. We included randomized controlled trials (RCTs) of participants undergoing surgery for RD associated with PVR that compared various tamponade agents. Two review authors screened the search results independently. We used the standard methodological procedures expected by The Cochrane Collaboration. The review included 516 participants from three RCTs. One study was conducted in the USA and consisted of two trials: the first trial randomized 151 adults to receive either silicone oil or sulfur hexafluoride (SF6) gas tamponades; and the second trial randomized 271 adults to receive either silicone oil or perfluropropane (C3F8) gas tamponades. The third trial was a multi-center international trial and randomized 94 participants (age range not specified) to receive heavy silicone oil (a mixture of perfluorohexyloctane (F6H8) and silicone oil) versus standard silicone oil (either 1000 centistokes or 5000 centistokes, per the surgeon's preference).In participants with RD associated with PVR, outcomes after pars plana vitrectomy and infusion of either silicone oil, perfluropropane gas, or sulfur hexafluoride gas appeared comparable for a broad variety of cases. There were no significant differences between silicone oil and perfluoropropane gas in terms of the proportion of participants achieving at least 5/200 visual acuity (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.73 to 1.31) or achieving macular attachment (RR 1.00; 95% CI 0.86 to 1.15) at a minimum of one year. Although sulfur hexafluoride gas was reported to be associated with significantly worse anatomic and visual outcomes than was silicone oil at one year (quantitative data not reported), there were no significant differences between silicone oil and sulfur hexafluoride gas in terms of achieving at least 5/200 visual acuity at two years (RR 1.57; 95% CI 0.93 to 2.66). For macular attachment, participants treated with silicone oil received significantly more favourable outcomes than did participants who received sulfur hexafluoride at both one year (quantitative data not reported) and two years (RR 1.37; 95% CI 1.01 to 1.86). The first two trials did not perform any sample size calculation or power detection. In the third trial, which had a power of 80% to detect differences, heavy silicone oil was not shown to be superior to standard silicone oil. There were no significant differences between standard silicone oil and heavy silicone oil in the change in visual acuity at one year using adjusted mean logMAR visual acuity (mean difference -0.03 logMAR; 95% CI -0.35 to 0.29). Adverse events were not reported for the first two trials. For the third trial, only the total number of adverse events was reported, and adverse events for each group were not specified. Of the 94 participants, four died, 26 had recurrent retinal detachment, 22 developed glaucoma, four developed a cataract, and two had capsular fibrosis.All three trials employed adequate methods for random sequence generation and allocation concealment. None of the trials employed masking of participants and surgeons, and only the third trial masked outcome assessors. The first trial had a large portion of participants excluded from the final analyses, while the other two trials were at low risk of attrition bias. All trials appear to be free of reporting bias. The first two trials were funded by the National Eye Institute, and the third trial was funded by the German Research Foundation. The use of either perfluropropane or standard silicone oil appears reasonable for most patients with RD associated with PVR. Because there do not appear to be any major differences in outcomes between the two agents, the choice of a tamponade agent should be individualized for each patient. Heavy silicone oil, which is not available for routine clinical use in the USA, has not demonstrated evidence of superiority over standard silicone oil.

Early Ambulation Predicts Length of Stay and Discharge Location Following Left Ventricular Assist Device Implantation

Purpose: No prior study has specifically investigated the effects of early mobility following left ventricular assist device (LVAD) implantation. The purpose of the present study was to describe postoperative acute care rehabilitation management of patients with LVADs and to determine whether earlier mobilization and ambulation were significant predictors of shorter length of stay (LOS) and discharge (DC) home. Methods: A retrospective chart review of the initial acute care stay of 98 consecutive patients with first-time HeartMate II or HeartWare LVAD implantation was performed. Multivariate linear and logistic regression models were used to control for the confounding effects of the following variables on LOS and DC home: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile, Model for End-Stage Liver Disease (MELD) score, serum albumin, number of postoperative days of impaired cognition, mechanical ventilation, and total number of adverse events. Results: The number of postoperative days until first ambulation was an independent, statistically significant predictor of both shorter LOS and likelihood of DC home, explaining an additional 15% of the variance in LOS and an additional 14% of the variance in the likelihood of DC home. The number of days until first time standing was not a statistically significant predictor of LOS or DC home. Conclusions: Earlier ambulation after LVAD implantation was predictive of shorter LOS and DC home even when controlling for several other well established pre- and postoperative determinants of clinical outcome.

Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth

Both paracetamol and ibuprofen are commonly used analgesics for the relief of pain following the surgical removal of lower wisdom teeth (third molars). In 2010, a novel analgesic (marketed as Nuromol) containing both paracetamol and ibuprofen in the same tablet was launched in the United Kingdom, this drug has shown promising results to date and we have chosen to also compare the combined drug with the single drugs using this model. In this review we investigated the optimal doses of both paracetamol and ibuprofen via comparison of both and via comparison with the novel combined drug. We have taken into account the side effect profile of the study drugs. This review will help oral surgeons to decide on which analgesic to prescribe following wisdom tooth removal. To compare the beneficial and harmful effects of paracetamol, ibuprofen and the novel combination of both in a single tablet for pain relief following the surgical removal of lower wisdom teeth, at different doses and administered postoperatively. We searched the Cochrane Oral Health Group'sTrials Register (to 20 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 4); MEDLINE via OVID (1946 to 20 May 2013); EMBASE via OVID (1980 to 20 May 2013) and the metaRegister of Controlled Trials (to 20 May 2013). We checked the bibliographies of relevant clinical trials and review articles for further studies. We wrote to authors of the identified randomised controlled trials (RCTs), and searched personal references in an attempt to identify unpublished or ongoing RCTs. No language restriction was applied to the searches of the electronic databases. Only randomised controlled double-blinded clinical trials were included. Cross-over studies were included provided there was a wash out period of at least 14 days. There had to be a direct comparison in the trial of two or more of the trial drugs at any dosage. All trials used the third molar pain model. All trials identified were scanned independently and in duplicate by two review authors, any disagreements were resolved by discussion, or if necessary a third review author was consulted. The proportion of patients with at least 50% pain relief (based on total pain relief (TOTPAR) and summed pain intensity difference (SPID) data) was calculated for all three drugs at both two and six hours postdosing and meta-analysed for comparison. The proportion of participants using rescue medication over both six and eight hours was also collated and compared. The number of patients experiencing adverse events or the total number of adverse events reported or both were analysed for comparison. Seven studies were included, they were all parallel-group studies, two studies were assessed as at low risk of bias and three at high risk of bias; two were considered to have unclear bias in their methodology. A total of 2241 participants were enrolled in these trials.Ibuprofen was found to be a superior analgesic to paracetamol at several doses with high quality evidence suggesting that ibuprofen 400 mg is superior to 1000 mg paracetamol based on pain relief (estimated from TOTPAR data) and the use of rescue medication meta-analyses. The risk ratio for at least 50% pain relief (based on TOTPAR) at six hours was 1.47 (95% confidence interval (CI) 1.28 to 1.69; five trials) favouring 400 mg ibuprofen over 1000 mg paracetamol, and the risk ratio for not using rescue medication (also favouring ibuprofen) was 1.50 (95% CI 1.25 to 1.79; four trials).The combined drug showed promising results, with a risk ratio for at least 50% of the maximum pain relief over six hours of 1.77 (95% CI 1.32 to 2.39) (paracetamol 1000 mg and ibuprofen 400 mg) (one trial; moderate quality evidence), and risk ratio not using rescue medication 1.60 (95% CI 1.36 to 1.88) (two trials; moderate quality evidence).The information available regarding adverse events from the studies (including nausea, vomiting, headaches and dizziness) indicated that they were comparable between the treatment groups. However, we could not formally analyse the data as it was not possible to work out how many adverse events there were in total. There is high quality evidence that ibuprofen is superior to paracetamol at doses of 200 mg to 512 mg and 600 mg to 1000 mg respectively based on pain relief and use of rescue medication data collected at six hours postoperatively. The majority of this evidence (five out of six trials) compared ibuprofen 400 mg with paracetamol 1000 mg, these are the most frequently prescribed doses in clinical practice. The novel combination drug is showing encouraging results based on the outcomes from two trials when compared to the single drugs.

Death Knell for Placebo-Controlled Trials in Chronic Idiopathic Constipation?

Death Knell for Placebo-Controlled Trials in Chronic Idiopathic Constipation?

Linaclotide: new mechanisms and new promise for treatment in constipation and irritable bowel syndrome

Chronic idiopathic constipation (CIC) and irritable bowel syndrome (IBS) are functional disorders of the lower gastrointestinal tract. Their prevalence in the general population is between 5% and 20%. Both disorders are chronic, with a relapsing and remitting natural history. The medical treatment of both conditions is unsatisfactory at present, and they represent a huge burden to the health service. Linaclotide is a first-in-class minimally adsorbed, 14-amino-acid peptide agonist of guanylate cyclase C. The drug acts on the intestinal enterocyte. As a consequence of this, intestinal fluid secretion is increased and intestinal transit is accelerated. The efficacy of linaclotide has been studied in both CIC and constipation-predominant IBS (IBS-C). Randomized controlled trials consistently demonstrate that the drug is effective in the treatment of CIC and IBS-C, across a wide range of continuous and dichotomous endpoints. The number needed to treat with linaclotide to prevent one patient with CIC or IBS-C failing to respond to therapy is between 5 and 8 in studies that have reported these data. Overall, in the majority of trials, total numbers of adverse events have been no more frequent with linaclotide, but rates of diarrhoea have been consistently higher. While the drug is clearly effective in the treatment of CIC, there are other evidence-based therapies available, and head-to-head efficacy and cost-effectiveness studies are therefore required to further delineate the role of linaclotide in the treatment of the condition. In IBS-C there are no other licensed therapies available, and linaclotide therefore represents a novel treatment with great promise.

Efficacy of Pharmacological Therapies for the Treatment of Opioid-Induced Constipation: Systematic Review and Meta-Analysis

There has been no definitive synthesis of the evidence for any benefit of available pharmacological therapies in opioid-induced constipation (OIC). We conducted a systematic review and meta-analysis to address this deficit. We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials through to December 2012 to identify placebo-controlled trials of μ-opioid receptor antagonists, prucalopride, lubiprostone, and linaclotide in the treatment of adults with OIC. No minimum duration of therapy was required. Trials had to report a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Effect of pharmacological therapies was reported as relative risk (RR) of failure to respond to therapy, with 95% confidence intervals (CIs). Fourteen eligible randomized controlled trials (RCTs) of μ-opioid receptor antagonists, containing 4,101 patients, were identified. These were superior to placebo for the treatment of OIC (RR of failure to respond to therapy=0.69; 95% CI 0.63-0.75). Methylnaltrexone (six RCTs, 1,610 patients, RR=0.66; 95% CI 0.54-0.84), naloxone (four trials, 798 patients, RR=0.64; 95% CI 0.56-0.72), and alvimopan (four RCTs, 1,693 patients, RR=0.71; 95% CI 0.65-0.78) were all superior to placebo. Total numbers of adverse events, diarrhea, and abdominal pain were significantly commoner when data from all RCTs were pooled. Reversal of analgesia did not occur more frequently with active therapy. Only one trial of prucalopride was identified, with a nonsignificant trend toward higher responder rates with active therapy. Two RCTs of lubiprostone were found, with significantly higher responder rates with lubiprostone in both, but reporting of data precluded meta-analysis. μ-Opioid receptor antagonists are safe and effective for the treatment of OIC. More data are required before the role of prucalopride or lubiprostone in the treatment of OIC are clear.

SAT0127 Long-Term Safety and Efficacy Following the Administration of Multiple Rituximab Cycles in Rheumatoid Arthritis (RA) Patients: The Multicenter, Prospective Launch Study

BackgroundAbout one third of RA patients do not initially respond to treatment with an anti-TNF agent whereas a similar rate demonstrates lack of efficacy over time. Rituximab/Mabthera administration (temporary B-lymphocyte...

OP0059 A Randomized Trial in New Onset Juvenile Dermatomyositis: Prednisone Versus Prednisone Plus Cyclosporine Versus Prednisone Plus Methotrexate

BackgroundData regarding the safety and efficacy of treatment regimens for juvenile dermatomyositis (JDM) tends to be from anecdotal, small, uncontrolled, non-randomized case series.ObjectivesThis randomized trial was aimed to find out...