Adding a new anticoagulant or antiplatelet agent for patient receiving aspirin after an acute coronary syndrome? - Results from a pairwise and network meta-analysis of randomized-controlled trials

 Objectives: To synthesize the efficacy and safety outcomes from randomized-controlled trials (RCTs) regarding new oral anticoagulant, protease-activated receptor-1 (PAR-1) antagonist, and warfarin adjunctive to aspirin for patients after acute coronary syndrome (ACS) via pair-wise and network meta-analyses.
Methods: A comprehensive literature search was performed in Embase, Medline, Cochrane Library Web of Knowledge, and Scopus. The pair-wise meta-analysis was undertaken respectively to each agent/treatment category via Revmen 5.1. In order to estimate the relative efficacy of each agent/treatment category whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in WinBUGS using both fixed- and random-effects model. Covariate analysis was performed to explore the effects of length of follow-up and age of subject on the final results.
Results: In total, 23 RCTs were included in the meta-analysis. As shown by the results (OR,95%CI) for the pair-wise meta-analysis, new oral anticoagulants (0.85, [0.78, 0.93] and 3.04, [2.21, 4.19]), PAR-1 antagonists (0.80, [0.52, 1.22] and 1.55, [1.25, 1.93]) and warfarin (0.87, [0.74, 1.02] and 1.77, [1.46, 2.14]) might be able to provide better outcome in the incidences of major adverse events (MAE) but with higher bleeding risk comparing to aspirin treatment alone. Based on the model fit assessment, the random-effects model was adopted. The network meta-analysis (treatment effect comparing to aspirin lone) identified ximelagatran (-0.3044, [-0.8601, 0.2502]), dabigatran (-0.2144, [-0.8666, 0.4525]), rivoroxaban (-0.2179, [-0.5986, 0.1628]) and vorapaxar (-0.2272, [-0.81, 0.1664]) produced better improvements in MAE incidences whereas vorapaxar (0.3764, [-0.4444, 1.124]), warfarin (0.663, [0.3375, 1.037]), ximelagatran (0.7509, [-0.4164, 2.002]) and apixaban (0.8594, [-0.0049, 1.7]) produced less major bleeding events. The indirect comparisons among drug category (difference in incidence comparing to aspirin lone) showed new oral anticoagulants (-0.1974, [-0.284, -0.111]) and PAR-1 antagonists (-0.1239, [-0.215, -0.033]) to besuperior to warfarin (-0.1004, [-0.166, -0.035]) in the occurrences of MAE whereas PAR-1 antagonists (0.4292, [0.2123, 0.6476]) afforded better outcomes in major bleeding events against warfarin (0.5742, [0.3889, 0.7619]) and new oral anticoagulants (1.169, [0.8667, 1.485]).
Conclusion: Based on the study results, we cannot recommend the routine administration of new oral anticoagulant as add-on treatment for patients after ACS. However, for ACS patients comorbid with atrial fibrillation, new oral anticoagulant might be superior to warfarin in both efficacy and safety outcomes.

Treatment with supplementary arginine, vitamin C and zinc in patients with pressure ulcers: A randomised controlled trial

Background & Aims
Nutrients putatively implicated in pressure ulcer healing were evaluated in a clinical setting.

Methods
Sixteen inpatients with a stage 2, 3 or 4 pressure ulcer randomised to receive daily a standard hospital diet; a standard diet plus two high-protein/energy supplements; or a standard diet plus two high-protein/energy supplements containing additional arginine (9 g), vitamin C (500 mg) and zinc (30 mg). Nutritional status measurements (dietary, anthropometric and biochemical) and pressure ulcer size and severity (by PUSH tool; Pressure Ulcer Scale for Healing; 0=completely healed, 17=greatest severity) were measured weekly for 3 weeks.

Results
Patients’ age and BMI ranges were 37–92 years and 16.4–28.1 kg/m2, respectively. Baseline PUSH scores were similar between groups (8.7±0.5). Only patients receiving additional arginine, vitamin C and zinc demonstrated a clinically significant improvement in pressure ulcer healing (9.4±1.2 vs. 2.6±0.6; baseline and week 3, respectively; P<0.01). All patient groups presented with low serum albumin and zinc and elevated C-reactive protein. There were no significant changes in biochemical markers, oral dietary intake or weight in any group.

Conclusions
In this small set of patients, supplementary arginine, vitamin C and zinc significantly improved the rate of pressure ulcer healing. The results need to be confirmed in a larger study.

Randomized controlled trial comparing traditional with two "mobile" epdural techniques

Background: The authors recently showed that “mobile” epidural analgesia, using low-dose local anesthetic–opioid mixtures, reduces the impact of epidural analgesia on instrumental vaginal delivery, relative to a traditional technique. The main prespecified assessment of pain relief efficacy, women’s postpartum estimates of labor pain after epidural insertion, did not differ. The detailed analgesic efficacy and the anesthetic characteristics of the techniques are reported here.
Methods: A total of 1,054 nulliparous women were randomized, in labor, to receive boluses of 10 ml 0.25% bupivacaine (traditional), combined spinal–epidural (CSE) analgesia, or lowdose infusion (LDI), the latter groups utilizing 0.1% bupivacaine with 2 g/ml fentanyl. Visual analog scale pain assessments were collected throughout labor and delivery and 24 h later. Details of the conduct of epidural analgesia, drug utilization, and requirement
for anesthesiologist reattendance were recorded.
Results: A total of 353 women were randomized to receive traditional epidural analgesia, 351 received CSE, and 350 received LDI. CSE was associated with a more rapid onset of analgesia, lower median visual analog scale pain scores than traditional in the first hour after epidural insertion, and a significant reduction in bupivacaine dose given during labor. Pain scores reported by women receiving LDI were similar to those in the traditional group throughout labor and delivery. Anesthesiologist reattendance was low but greater with each mobile technique.
Conclusions: Relative to traditional epidural analgesia, LDI is at least as effective and CSE provided better pain relief in the early stages after insertion. The proven efficacy of mobile epidurals and their beneficial impact on delivery mode make them the preferred techniques for epidural pain relief in labor.

Effect of low-dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial

Background

Epidural analgesia is the most effective labour pain relief but is associated with increased rates of instrumental vaginal delivery and other effects, which might be related to the poor motor function associated with traditional epidural. New techniques that preserve motor function could reduce obstetric intervention. We did a randomised controlled trial to compare low-dose combined spinal epidural and low-dose infusion (mobile) techniques with traditional epidural technique.
Methods

Between Feb 1, 1999, and April 30, 2000, we randomly assigned 1054 nulliparous women requesting epidural pain relief to traditional (n=353), low-dose combined spinal epidural (n=351), or low-dose infusion epidural (n=350). Primary outcome was mode of delivery, and secondary outcomes were progress of labour, efficacy of procedure, and effect on neonates. We obtained data during labour and interviewed women postnatally.
Findings

The normal vaginal delivery rate was 35·1% in the traditional epidural group, 42·7% in the low-dose combined spinal group (odds ratio 1·38 [95% CI 1·01–1·89]; p=0·04); and 42·9% in the low-dose infusion group (1·39 [1·01–1·90]; p=0·04). These differences were accounted for by a reduction in instrumental vaginal delivery. Overall, 5 min APGAR scores of 7 or less were more frequent with low-dose technique. High-level resuscitation was more frequent in the low-dose infusion group.

Extent of heart failure self-care as an endpoint to patient education: a literature review

Background: In western countries the number of chronic heart failure (CHF) management programs has escalated in recent times. One key component of them is to teach self-care behaviours that enable affected individuals to monitor themselves and engage in lifestyles that improve their health status.
Aim: The aim of this article is to describe CHF self-care management and to review the literature which examines the effectiveness of patient education on patients’ performance of self-care behaviours.
Design/method: bibliographical databases were searched for papers published in English between 1982 to 2006. The search used the key words: heart failure, education, self-care and measures. Only randomized controlled trials (RCTs) were selected.
Results: Ten randomized controlled trials were selected that used education as an intervention and, in total, 1064 patients with CHF participated in these studies. The studies were heterogenous as to the sample population, the health outcomes measured, the education interventions, the expertise of the educator, and the length of time that was spent on teaching patients. No consistent patterns of implementation and specific evaluation of its impact were found, although three respective groups of investigators reported signifi cant differences in recurrent hospitalisation rates and mortality rates which were relative to usual care.
Conclusions: Teaching patients appropriate CHF self-care behaviours can significantly improve their health outcomes. Improvements in self-care were demonstrated in seven studies but only three had used validated instruments to measure such changes. This suggests that no firm conclusions can be drawn about changes in self-care practices.

A randomized controlled trial of buprenorphine in the management of short-term ambulatory heroin withdrawal

Aim: To determine whether buprenorphine is more effective than clondine and other symptomatic medications in managing ambulatory heroin withdrawal.
Design: Open label. prospective randomized controlled trial examining
withdrawal and 4-week postwithdrawal outcomes on intention-to-treat.
Setting: Two specialist, out-patient drug treatment centres in inner city
Melbourne and Sydney, Australia.
Participants: One hundred and fourteen dependent heroin users were recruited. Participants were 18 yea rs or over. and with no significant other drug dependence, medical or psychiatric conditions or recent methadone treatment. One hundred and one (89%) participants completed a day 8 research interview examining withdrawal outcomes, and 92 (81%) completed day 35 research interview examining postwithdrawal outcomes.
Interventions: Participants randomized to control (n = 56) (up to 8 days or
clonidine and other symptomatic medications) or experimental (n = 58) (up to 5 days of buprenorphine) withdrawal groups. Following the 8-day withdrawal episode, participants could self-select from range of postwithdrawal options (naltrexone, substitution maintenance or counselling).
Measurements: Retention in withdrawal: heroin use during withdrawl: and
retention in drug treatment 4 weeks after withdrawal.
Secondary outcomes: Withdrawal severity: adverse events, and heroin use in the postwithdrawal period.
Findings: The experimental group had better treatment retention at day 8 (86% versus 57%, P = 0.001, 95% CI for numbers needed to treat (NNT) = 3-8) and day 35 (62% versus 39%, P = 0.02, 95% CI for NNT = 4-18): used heroin on fewer days during the withdralwal programlme (2.6 ± 2.5 versus 4.5 ± 2. 3.
P < 0.001. 95% CI = 1- 2.5 days) and in the postwithdrawal period (9.0±8.2
versus 14.6± 10. P<O.Ol. 95% CI = I .8- 9.4): and reported less withdrawal
severity. No severe adverse events reported.
Conclusions: Buprenorphine is effective for short-term ambulatory heroin
withdrawaI, with greater retention, less heroin use and less withdrawal discomfort during withdrawal: and increased postwithdrawal treatment retention than symptomatic medications.

Sedation and analgesia management for mechanically ventilated adults: literature review, case study and recommentations for practice.

The quality of sedation management in mechanically ventilated patients has been a source of concern in recent years. This paper summarises the literature on the principles of optimal sedation, discusses the consequences of over and undersedation, highlighting the importance of appropriate pain management, and presents a case study using the results of an audit of 48 mechanically ventilated adults. As a result of the review and audit, we are implementing changes to practice.

The most important recommendations from the literature are the use of a sedation scale, setting of a goal sedation score, appropriate pain management and implementation of a nurse initiated sedation algorithm. Other recommendations include use of bolus rather than continuous sedative infusions and recommencing regular medications for anxiety, depression and other phychiatric disorders as soon as possible. A recommendation arising from our audit was the need to identify patients at high risk of oversedation and undersedation and adopt a proactive rather than reactive approach to management. The practice goal is to provide adequate and appropriate analgesia and anxiolysis for patients. This will improve patient comfort while reducing length of mechanical ventilation and minimising risk of complications.

Economic evaluation alongside a phase II, multi-centre, randomised controlled trial of very early rehabilitation after stroke (AVERT)

BACKGROUND/PURPOSE: The effectiveness and costs of very early rehabilitation after stroke are unknown. This study assessed the cost effectiveness of very early mobilisation in addition to standard care (VEM) compared with standard care alone (SC). METHODS: Cost-effectiveness analysis alongside a phase II, multi-centre, randomised controlled trial (RCT) with blinded outcome assessments. Less than 24 h after stroke, patients were recruited from two stroke units and randomised to receive VEM or SC. The intervention continued until discharge or 14 days, whichever was sooner. The efficacy measure was a dichotomised modified Rankin Scale (mRS) at 3 months with mRS < or =2 representing good outcome. Costs were determined from medical records and patient interviews at 3, 6 and 12 months. National average (where available) or local costs were applied for the reference year 2004. Differences in mean total costs at 3 and 12 months were tested using t test assuming unequal variances. An incremental cost-effectiveness ratio was calculated and probabilistic uncertainty analysis was undertaken. RESULTS: The sample consisted of 38 VEM and 33 SC patients. A trend for good outcome with VEM compared to SC was found (adjusted OR 4.10, 95% CI 0.99-16.88, p = 0.051). Patients receiving VEM incurred significantly less costs at 3 months (AUD 13,559) compared with SC (AUD 21,860; p = 0.02). This difference in mean per patient total cost persisted at the 12-month assessment (VEM: AUD 17,564; SC: AUD 29,750; p = 0.03). VEM was found to be a 'dominant' (more effective, less cost) intervention when compared to SC at 3 months. CONCLUSION: These findings provide preliminary evidence that VEM is likely to be cost-effective. A large RCT is currently underway to confirm the cost effectiveness of VEM.

A controlled trial of internet-based cognitive-behavioural therapy for panic disorder with face-to-face support from a general practitioner or email support from a psychologist

Background: Panic disorder (PD) is one of the most common anxiety disorders seen in general practice, but provision of evidence-based cognitive-behavioural treatment (CBT) is rare. Many Australian GPs are now trained to deliver focused psychological strategies, but in practice this is time consuming and costly.

Objective: To evaluate the efficacy of an internet-based CBT intervention (Panic Online) for the treatment of PD supported by general practitioner (GP)-delivered therapeutic assistance.

Design: Panic Online supported by GP-delivered face-to-face therapy was compared to Panic Online supported by psychologist-delivered email therapy.

Methods: Sixty-five people with a primary diagnosis of PD (78% of whom also had agoraphobia) completed 12 weeks of therapy using Panic Online and therapeutic assistance with his/her GP (n = 34) or a clinical psychologist (n = 31). The mean duration of PD for participants allocated to these groups was 59 months and 58 months, respectively. Participants completed a clinical diagnostic interview delivered by a psychologist via telephone and questionnaires to assess panic-related symptoms, before and after treatment.

Results: The total attrition rate was 20%, with no group differences in attrition frequency. Both treatments led to significant improvements in panic attack frequency, depression, anxiety, stress, anxiety sensitivity and quality of life. There were no statistically significant differences in the two treatments on any of these measures, or in the frequency of participants with clinically significant PD at post assessment.

Conclusions: When provided with accessible online treatment protocols, GPs trained to deliver focused psychological strategies can achieve patient outcomes comparable to efficacious treatments delivered by clinical psychologists. The findings of this research provide a model for how GPs may be assisted to provide evidence-based mental healthcare successfully.

Patient education to prevent falls in subacute care

Objective: To evaluate the effectiveness of a patient education programme for preventing falls in the subacute hospital setting.

Design: Randomized controlled trial, subgroup analysis.

Participants: Patients of a metropolitan subacute/aged rehabilitation hospital who were recommended for a patient education intervention for the prevention of falls when enrolled in a larger randomized controlled trial of a falls prevention programme.

Methods: Participants in both the control and intervention groups who were recommended for the education programme intervention were followed for the duration of their hospital stay to determine if falls occurred. Only participants in the intervention group who were recommended for this intervention actually received it. In addition, these participants completed an evaluation survey at the completion of their education programme.

Results: Intervention group participants in this subgroup analysis had a significantly lower incidence of falls than their control group counterparts (control: 16.0 falls/1000 participant-days, intervention: 8.2 falls/1000 participant-days, log-rank test: P = 0.007). However the difference in the proportion of fallers was not significant (relative risk 1.21, 95% confidence interval 0.68 to 2.14).

Conclusion: Patient education is an important part of a multiple intervention falls prevention approach for the subacute hospital setting.

Does an evidence-based sedation protocol improve practice and patient outcomes in critical care?

Learning Objective 1: compare protocol-directed sedation management with traditional non-protocol-directed practice in mechanically ventilated patients in an Australian critical care.

Learning Objective 2: explain the contrasting international research findings on sedation protocol implementation.
Minimization of sedation in critical care patients has recently received widespread support. Professional organizations internationally have published sedation management guidelines for critically ill patients to improve the use of research in practice, decrease practice variability and shorten mechanical ventilation duration. Innovations in practice have included the introduction of decision making protocols, daily sedation interruptions and new drugs and monitoring technologies. The aim of this study was to compare protocol-directed sedation management with traditional non-protocol-directed practice in mechanically ventilated patients in an Australian critical care setting.

A randomized, controlled trial design was used to study 312 mechanically ventilated adult patients in a general critical care unit at an Australian metropolitan teaching hospital. Patients were randomly assigned to receive protocol directed sedation management developed from evidence based guidelines (n=153) or usual clinical practice (n=159).

The median (95% CI) duration of ventilation was 58 hrs (44–78 hrs) for patients in the non-protocol group and 79 hrs (56–93) for those patients in the protocol group (p=0.20). Results were not significant for length of stay in critical care or hospital, the frequency of tracheostomies, and unplanned extubations. A Cox proportional hazards model estimated that protocol directed sedation management was associated with a 22% decrease (95% CI: 40% decrease to 2% increase, p=0.07) in the occurrence of successful weaning from mechanical ventilation.

Few randomized controlled trials have evaluated the effectiveness of protocol-directed sedation outside of North America. This study highlights the lack of transferability between different settings and different models of care. Qualified, high intensity nursing in the Australian critical care setting facilitates rapid, responsive decisions for sedation management and an increased success rate for weaning from mechanical ventilation.

Cost-efficacy of surgically induced weight loss for the management of type 2 diabetes : a randomized controlled trial

OBJECTIVE -- To determine the within-trial cost-efficacy of surgical therapy relative to conventional therapy for achieving remission of recently diagnosed type 2 diabetes in class I and II obese patients.

RESEARCH DESIGN AND METHODS -- Efficacy results were derived from a 2-year randomized controlled trial. A health sector perspective was adopted, and within-trial intervention costs included gastric banding surgery, mitigation of complications, outpatient medical consultations, medical investigations, pathology, weight loss therapies, and medication. Resource use was measured based on data drawn from a trial database and patient medical records and valued based on private hospital costs and government schedules in 2006 Australian dollars (AUD). An incremental cost-effectiveness analysis was undertaken.

RESULTS -- Mean 2-year intervention costs per patient were 13,400 AUD for surgical therapy and 3,400 AUD for conventional therapy, with laparoscopic adjustable gastric band (LAGB) surgery accounting for 85% of the difference. Outpatient medical consultation costs were three times higher for surgical patients, whereas medication costs were 1.5 times higher for conventional patients. The cost differences were primarily in the first 6 months of the trial. Relative to conventional therapy, the incremental cost-effectiveness ratio for surgical therapy was 16,600 AUD per case of diabetes remitted (currency exchange: 1 AUD = 0.74 USD).

CONCLUSIONS -- Surgical therapy appears to be a cost-effective option for managing type 2 diabetes in class I and II obese patients.

Efficacy and safety of vertebroplasty for treatment of painful osteoporotic vertebral fractures : a randomised double-blind placebo-controlled trial

Background: Vertebroplasty has become a common treatment for painful osteoporotic vertebral fractures despite limited evidence to support its use. The primary aim of this study was to determine its short-term efficacy and safety in this patient population.

Methods: In a multicentre randomized placebo-controlled trial, participants with one or two painful osteoporotic vertebral fractures < 12 months duration confirmed active by MRI were randomly assigned, stratified by center, gender and duration of symptoms (< or ≥ 6 weeks), to receive vertebroplasty or sham treatment. Primary outcome was overall pain (0–10 scale) at 3 months. Participants, investigators (other than the interventional radiologist) and outcome assessors were blinded to treatment assignment.

Results: 78 participants were enrolled and 73 (36/38 active, 37/40 placebo, 94%) completed 3-month follow up. Vertebroplasty did not show any statistically significant advantage in any measured outcome with 95% confidence intervals indicating no plausible practically important benefits of vertebroplasty over placebo. At 1 week, 1 and 3 months, there were significant improvements in overall pain in both treatment groups (mean improvement (SD): 1.5 (2.5), 2.1 (2.8), 2.3 (2.6), and 1.7 (3.3), 2.5 (2.9), 1.9 (3.4) in the active and placebo groups respectively). Similar improvements in both groups were observed for night and rest pain, function, quality of life and perceived improvement. Eight incident clinical vertebral fractures (3 active, 5 placebo) occurred during 3-month follow up.

Conclusion: We found no evidence of a beneficial effect of vertebroplasty over sham treatment for painful osteoporotic vertebral fractures, 1 week, 1 and 3 months following treatment. [Australian Clinical Trial Register number, ACTRN012605000079640]

Effectiveness of a community-based osteoporosis education and self-management course : a wait list controlled trial

Summary : Osteoporosis is an increasing burden on individuals and health resources. The Osteoporosis Prevention and Self-Management Course (OPSMC) was designed to assist individuals to prevent and manage osteoporosis; however, it had not been evaluated in an Australian setting. This randomised controlled trial showed that the course increased osteoporosis knowledge.
Introduction and hypothesis : Osteoporosis is a major and growing public health concern. An OPSMC was designed to provide individuals with information and skills to prevent or manage osteoporosis, but its effectiveness has not previously been evaluated. This study aimed to determine whether OPSMC attendance improved osteoporosis knowledge, self-efficacy, self-management skills or behaviour.
Materials and methods : Using a wait list randomised controlled trial design, 198 people (92% female) recruited from the community and aged over 40 (mean age = 63) were randomised into control (n = 95) and intervention (n = 103) groups. The OPSMC consists of four weekly sessions which run for 2 h and are led by two facilitators. The primary outcome were osteoporosis knowledge, health-directed behaviour, self-monitoring and insight and self-efficacy.
Results : The groups were comparable at baseline. At 6-week follow-up, the intervention group showed a significant increase in osteoporosis knowledge compared with the control group; mean change 3.5 (p < 0.001) on a measure of 0–20. The intervention group also demonstrated a larger increase in health-directed behaviour, mean change 0.16 (p < 0.05), on a measure of 0–6.
Conclusion : The results indicate that the OPSMC is an effective intervention for improving understanding of osteoporosis and some aspects of behaviour in the short term.

Getting your life back on track after stroke : a phase II multi-centered, single-blind, randomized, controlled trial of the Stroke Self-Management Program vs. the Stanford Chronic Condition Self-Management Program or standard care in stroke survivors

Background Self-management is seen as a primary mechanism to support the optimization of care for people with chronic diseases such as symptomatic vascular disease. There are no established and evidence-based stroke-specific chronic disease self-management programs. Our aim is to evaluate whether a stroke-specific program is safe and feasible as part of a Phase II randomized-controlled clinical trial.
Methods Stroke survivors are recruited from a variety of sources including: hospital stroke services, local paper advertisements, Stroke South Australia newsletter (volunteer peer support organization), Divisions of General Practice, and community service providers across Adelaide, South Australia. Subjects are invited to participate in a multi-center, single-blind, randomized, controlled trial. Eligible participants are randomized to either;
• standard care,
• standard care plus a six week generic chronic condition self-management group education program, or,
• standard care plus an eight week stroke specific self-management education group program.
Interventions are conducted after discharge from hospital. Participants are assessed at baseline, immediate post intervention and six months.
Study Outcomes The primary outcome measures determine study feasibility and safety, measuring, recruitment, participation, compliance and adverse events.
Secondary outcomes include:
• positive and active engagement in life measured by the Health Education Impact Questionnaire,
• improvements in quality of life measured by the Assessment of Quality of Life instrument,
• improvements in mood measured by the Irritability, Depression and Anxiety Scale,
• health resource utilization measured by a participant held diary and safety.

Conclusion The results of this study will determine whether a definitive Phase III efficacy trial is justified.