Pre-referral rectal artesunate in severe malaria: flawed trial

Introduction

Irritable bowel syndrome affects as many as 14% of high school-aged students. Symptoms include discomfort in the abdomen, along with diarrhea and/or constipation and other gastroenterological symptoms that can significantly impact quality of life and daily functioning. Emotional stress appears to exacerbate irritable bowel syndrome symptoms suggesting that mind-body interventions reducing arousal may prove beneficial. For many sufferers, symptoms can be traced to childhood and adolescence, making the early manifestation of irritable bowel syndrome important to understand. The current study will focus on young people aged 14-26 years with irritable bowel syndrome. The study will test the potential benefits of Iyengar yoga on clinical symptoms, psychospiritual functioning and visceral sensitivity. Yoga is thought to bring physical, psychological and spiritual benefits to practitioners and has been associated with reduced stress and pain. Through its focus on restoration and use of props, Iyengar yoga is especially designed to decrease arousal and promote psychospiritual resources in physically compromised individuals. An extensive and standardized teacher-training program support Iyengar yoga's reliability and safety. It is hypothesized that yoga will be feasible with less than 20% attrition; and the yoga group will demonstrate significantly improved outcomes compared to controls, with physiological and psychospiritual mechanisms contributing to improvements.

Methods/Design

Sixty irritable bowel syndrome patients aged 14-26 will be randomly assigned to a standardized 6-week twice weekly Iyengar yoga group-based program or a wait-list usual care control group. The groups will be compared on the primary clinical outcomes of irritable bowel syndrome symptoms, quality of life and global improvement at post-treatment and 2-month follow-up. Secondary outcomes will include visceral pain sensitivity assessed with a standardized laboratory task (water load task), functional disability and psychospiritual variables including catastrophizing, self-efficacy, mood, acceptance and mindfulness. Mechanisms of action involved in the proposed beneficial effects of yoga upon clinical outcomes will be explored, and include the mediating effects of visceral sensitivity, increased psychospiritual resources, regulated autonomic nervous system responses and regulated hormonal stress response assessed via salivary cortisol.

Trial registration

ClinicalTrials.gov NCT01107977.     

Comparison of embedded and added motor imagery training in patients after stroke: results of a randomised controlled pilot trial

Background

Motor imagery (MI) when combined with physiotherapy can offer functional benefits after stroke. Two MI integration strategies exist: added and embedded MI. Both approaches were compared when learning a complex motor task (MT): 'Going down, laying on the floor, and getting up again'.

Methods

Outpatients after first stroke participated in a single-blinded, randomised controlled trial with MI embedded into physiotherapy (EG1), MI added to physiotherapy (EG2), and a control group (CG). All groups participated in six physiotherapy sessions. Primary study outcome was time (sec) to perform the motor task at pre and post-intervention. Secondary outcomes: level of help needed, stages of MT-completion, independence, balance, fear of falling (FOF), MI ability. Data were collected four times: twice during one week baseline phase (BL, T0), following the two week intervention (T1), after a two week follow-up (FU). Analysis of variance was performed.

Results

Thirty nine outpatients were included (12 females, age: 63.4 ± 10 years; time since stroke: 3.5 ± 2 years; 29 with an ischemic event). All were able to complete the motor task using the standardised 7-step procedure and reduced FOF at T0, T1, and FU. Times to perform the MT at baseline were 44.2 ± 22s, 64.6 ± 50s, and 118.3 ± 93s for EG1 (N = 13), EG2 (N = 12), and CG (N = 14). All groups showed significant improvement in time to complete the MT (p < 0.001) and degree of help needed to perform the task: minimal assistance to supervision (CG) and independent performance (EG1+2). No between group differences were found. Only EG1 demonstrated changes in MI ability over time with the visual indicator increasing from T0 to T1 and decreasing from T1 to FU. The kinaesthetic indicator increased from T1 to FU. Patients indicated to value the MI training and continued using MI for other difficult-to-perform tasks.

Conclusions

Embedded or added MI training combined with physiotherapy seem to be feasible and benefi-cial to learn the MT with emphasis on getting up independently. Based on their baseline level CG had the highest potential to improve outcomes. A patient study with 35 patients per group could give a conclusive answer of a superior MI integration strategy.

Trial Registration

ClinicalTrials.gov: NCT00858910     

Effect of repaglinide on endothelial dysfunction during a glucose tolerance test in subjects with impaired glucose tolerance

Background

Secondary treatment of arteriosclerosis may be applicable for the primary prevention of atherosclerosis in diabetic patients. This prospective, 2-year follow-up study was designed to determine the efficacy and safety of antiplatelet therapy in the prevention of atherosclerosis of diabetic subjects.

Methods

Patients with type 2 diabetes and arteriosclerosis obliterans from the Eastern Asian countries were registered online and randomly assigned either to the aspirin group (81–100 mg/day) or the cilostazol group (100–200 mg/day) in this international, 2-year, prospective follow-up interventional study.

Results

The primary study endpoint was changes in right and left maximum intima-media thickness of the common carotid artery. Secondary endpoints include changes in right and left maximum intima-media thickness of the internal carotid artery; semiquantitative evaluation of cerebral infarction by magnetic resonance imaging; cardiovascular events including sudden death, stroke, transient cerebral ischemic attacks, acute myocardial infarction, angina, and progression of arteriosclerosis obliterans; overall death; withdrawal; and change in ankle-brachial pressure index.

Conclusion

This is the first study to use an online system that was developed in Asian countries for pooling data from an international clinical trial. These findings are expected to help in the prevention of diabetic atherosclerosis and subsequent cardiovascular and cerebrovascular disease.     

The Rx for Change database: a first-in-class tool for optimal prescribing and medicines use

Background

Survivors of transient ischemic attack (TIA) or stroke are at high risk for recurrent vascular events and aggressive treatment of vascular risk factors can reduce this risk. However, vascular risk factors, especially hypertension and high cholesterol, are not managed optimally even in those patients seen in specialized clinics. This gap between the evidence for secondary prevention of stroke and the clinical reality leads to suboptimal patient outcomes. In this study, we will be testing a pharmacist case manager for delivery of stroke prevention services. We hypothesize this new structure will improve processes of care which in turn should lead to improved outcomes.

Methods

We will conduct a prospective, randomized, controlled open-label with blinded ascertainment of outcomes (PROBE) trial. Treatment allocation will be concealed from the study personnel, and all outcomes will be collected in an independent and blinded manner by observers who have not been involved in the patient's clinical care or trial participation and who are masked to baseline measurements. Patients will be randomized to control or a pharmacist case manager treating vascular risk factors to guideline-recommended target levels. Eligible patients will include all adult patients seen at stroke prevention clinics in Edmonton, Alberta after an ischemic stroke or TIA who have uncontrolled hypertension (defined as systolic blood pressure (BP) > 140 mm Hg) or dyslipidemia (fasting LDL-cholesterol > 2.00 mmol/L) and who are not cognitively impaired or institutionalized. The primary outcome will be the proportion of subjects who attain 'optimal BP and lipid control'(defined as systolic BP < 140 mm Hg and fasting LDL cholesterol < 2.0 mmol/L) at six months compared to baseline; 12-month data will also be collected for analyses of sustainability of any effects. A variety of secondary outcomes related to vascular risk and health-related quality of life will also be collected.

Conclusions

Nearly one-quarter of those who survive a TIA or minor stroke suffer another vascular event within a year. If our intervention improves the provision of secondary prevention therapies in these patients, the clinical (and financial) implications will be enormous.     

Case management for blood pressure and lipid level control after minor stroke: PREVENTION randomized controlled trial

Background:

Optimization of systolic blood pressure and lipid levels are essential for secondary prevention after ischemic stroke, but there are substantial gaps in care, which could be addressed by nurse- or pharmacist-led care. We compared 2 types of case management (active prescribing by pharmacists or nurse-led screening and feedback to primary care physicians) in addition to usual care.

Methods:

We performed a prospective randomized controlled trial involving adults with recent minor ischemic stroke or transient ischemic attack whose systolic blood pressure or lipid levels were above guideline targets. Participants in both groups had a monthly visit for 6 months with either a nurse or pharmacist. Nurses measured cardiovascular risk factors, counselled patients and faxed results to primary care physicians (active control). Pharmacists did all of the above as well as prescribed according to treatment algorithms (intervention).

Results:

Most of the 279 study participants (mean age 67.6 yr, mean systolic blood pressure 134 mm Hg, mean low-density lipoprotein [LDL] cholesterol 3.23 mmol/L) were already receiving treatment at baseline (antihypertensives: 78.1%; statins: 84.6%), but none met guideline targets (systolic blood pressure ≤ 140 mm Hg, fasting LDL cholesterol ≤ 2.0 mmol/L). Substantial improvements were observed in both groups after 6 months: 43.4% of participants in the pharmacist case manager group met both systolic blood pressure and LDL guideline targets compared with 30.9% in the nurse-led group (12.5% absolute difference; number needed to treat = 8, p = 0.03).

Interpretation:

Compared with nurse-led case management (risk factor evaluation, counselling and feedback to primary care providers), active case management by pharmacists substantially improved risk factor control at 6 months among patients who had experienced a stroke. Trial registration: ClinicalTrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT00931788","term_id":"NCT00931788"}}NCT00931788The risk of cardiovascular events is high for patients who survive a stroke or transient ischemic attack.^1,2 Treatment of hypertension and dyslipidemia can substantially reduce this risk.^3–7 However, vascular risk factors are often suboptimally managed after stroke or transient ischemic attack, even among patients admitted to hospital or seen in specialized stroke prevention clinics.^8–10Multiple barriers are responsible for the suboptimal control of risk factors, and traditional means of educating practitioners and patients have limited effectiveness.¹¹ Although it has been suggested that “case managers” may be able to improve the management of risk factors, evidence is sparse and inconsistent between studies.^12–16 The most recent Cochrane review on this topic concluded that “nurse- or pharmacist-led care may be a promising way forward … but these interventions require further evaluation.”¹⁶ Thus, we designed this trial to evaluate whether a pharmacist case manager could improve risk factors among survivors of stroke or transient ischemic attack.¹⁷ Because we have previously shown that hypertension control can be improved by monthly evaluation by nurses (with patient counselling and faxing of blood pressure measurements with guideline recommendations to primary care physicians),¹⁸ and this is an alternate method of case management implemented in many health organizations, we used this approach as the active control group for this study. Thus, our study represents a controlled comparison of 2 modes of case management: active prescribing (pharmacist-led case management) versus screening and delegating to primary care physicians (nurse-led case management).     

Neuroserpin polymorphisms and stroke risk in a biracial population: the stroke prevention in young women study

Background

Neuroserpin, primarily localized to CNS neurons, inhibits the adverse effects of tissue-type plasminogen activator (tPA) on the neurovascular unit and has neuroprotective effects in animal models of ischemic stroke. We sought to evaluate the association of neuroserpin polymorphisms with risk for ischemic stroke among young women.

Methods

A population-based case-control study of stroke among women aged 15–49 identified 224 cases of first ischemic stroke (47.3% African-American) and 211 age-matched control subjects (43.1% African-American). Neuroserpin single nucleotide polymorphisms (SNPs) chosen through HapMap were genotyped in the study population and assessed for association with stroke.

Results

Of the five SNPs analyzed, the A allele (frequency; Caucasian = 0.56, African-American = 0.42) of SNP rs6797312 located in intron 1 was associated with stroke in an age-adjusted dominant model (AA and AT vs. TT) among Caucasians (OR = 2.05, p = 0.023) but not African-Americans (OR = 0.71, p = 0.387). Models adjusting for other risk factors strengthened the association. Race-specific haplotype analyses, inclusive of SNP rs6797312, again demonstrated significant associations with stroke among Caucasians only.

Conclusion

This study provides the first evidence that neuroserpin is associated with early-onset ischemic stroke among Caucasian women.     

Home blood pressure monitoring with nurse-led telephone support among patients with hypertension and a history of stroke: a community-based randomized controlled trial

Background:

Adequate control of blood pressure reduces the risk of recurrent stroke. We conducted a randomized controlled study to determine whether home blood pressure monitoring with nurse-led telephone support would reduce blood pressure in patients with hypertension and a history of stroke.

Methods:

We recruited 381 participants (mean age 72 years) from outpatient and inpatient stroke clinics between Mar. 1, 2007, and Aug. 31, 2009. Nearly half (45%, 170) of the participants had some disability due to stroke. Participants were visited at home for a baseline assessment and randomly allocated to home blood pressure monitoring (n = 187) or usual care (n = 194). Those in the intervention group were given a monitor, brief training and telephone support. Participants who had home blood pressure readings consistently over target (target < 130/80 mm Hg) were advised to consult their family physician. The main outcome measure was a fall in systolic blood pressure after 12 months, measured by an independent researcher unaware of group allocation.

Results:

Despite more patients in the intervention group than in the control group having changes to antihypertensive treatment during the trial period (60.1% [98/163] v. 47.6% [78/164], p = 0.02), the fall in systolic blood pressure from baseline did not differ significantly between the groups (adjusted mean difference 0.3 mm Hg, 95% confidence interval –3.6 to 4.2 mm Hg). Subgroup analysis showed significant interaction with disability due to stroke (p = 0.03 at 6 months) and baseline blood pressure (p = 0.03 at 12 months).

Interpretation:

Overall, home monitoring did not improve blood pressure control in patients with hypertension and a history of stroke. It was associated with a fall in systolic pressure in patients who had uncontrolled blood pressure at baseline and those without disability due to stroke. Trial registration: ClinicalTrials.gov registration {"type":"clinical-trial","attrs":{"text":"NCT00514800","term_id":"NCT00514800"}}NCT00514800Worldwide about 15 million people have a stroke each year.¹ Adequate control of blood pressure reduces the risk of recurrent stroke by up to 40%.² However, about 1 in 3 adults have blood pressure readings above recommended targets.³ Systematic reviews suggest that home monitoring is associated with reduced blood pressure^4–7 and may improve compliance with treatment and encourage lifestyle changes.⁸ But the benefits tend to be modest.^4,5 Co-interventions, such as patient education and support from health professionals, are important and may lead to intensification of antihypertensive treatment.^8,9Despite the importance of good control of blood pressure in patients with a history of stroke, little is known about home monitoring in this group. Physical and cognitive impairments resulting from stroke may adversely affect patients’ compliance and ability to use the equipment successfully. We conducted a randomized controlled trial to determine whether home blood pressure monitoring with nurse-led telephone support was associated with reduced systolic blood pressure after 12 months in patients with hypertension and a history of stroke. Because PROGRESS (the Perindopril Protection Against Recurrent Stroke Study)² showed that antihypertensive medications reduced the risk of recurrent stroke among patients with or without hypertension who had a history of stroke, we aimed to assess home monitoring in unselected patients with hypertension and a history of stroke across the blood pressure range.     

Study protocol of the YOU CALL - WE CALL TRIAL: impact of a multimodal support intervention after a "mild" stroke

Background

More than 60% of new strokes each year are "mild" in severity and this proportion is expected to rise in the years to come. Within our current health care system those with "mild" stroke are typically discharged home within days, without further referral to health or rehabilitation services other than advice to see their family physician. Those with mild stroke often have limited access to support from health professionals with stroke-specific knowledge who would typically provide critical information on topics such as secondary stroke prevention, community reintegration, medication counselling and problem solving with regard to specific concerns that arise. Isolation and lack of knowledge may lead to a worsening of health problems including stroke recurrence and unnecessary and costly health care utilization. The purpose of this study is to assess the effectiveness, for individuals who experience a first "mild" stroke, of a sustainable, low cost, multimodal support intervention (comprising information, education and telephone support) - "WE CALL" compared to a passive intervention (providing the name and phone number of a resource person available if they feel the need to) - "YOU CALL", on two primary outcomes: unplanned-use of health services for negative events and quality of life.

Method/Design

We will recruit 384 adults who meet inclusion criteria for a first mild stroke across six Canadian sites. Baseline measures will be taken within the first month after stroke onset. Participants will be stratified according to comorbidity level and randomised to one of two groups: YOU CALL or WE CALL. Both interventions will be offered over a six months period. Primary outcomes include unplanned use of heath services for negative event (frequency calendar) and quality of life (EQ-5D and Quality of Life Index). Secondary outcomes include participation level (LIFE-H), depression (Beck Depression Inventory II) and use of health services for health promotion or prevention (frequency calendar). Blind assessors will gather data at mid-intervention, end of intervention and one year follow up.

Discussion

If effective, this multimodal intervention could be delivered in both urban and rural environments. For example, existing infrastructure such as regional stroke centers and existing secondary stroke prevention clinics, make this intervention, if effective, deliverable and sustainable.

Trial Registration

ISRCTN95662526     

PISA. The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: Protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690]

Background

During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily) and low dose (3 g daily) paracetamol (acetaminophen) in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4°C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied.

Aim

The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments.

Design

Seventy-five (3 × 25) patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out.     

Atrial fibrillation is not uncommon among patients with ischemic stroke and transient ischemic stroke in China

Background

Atrial fibrillation (AF) is reported to be a less frequent cause of ischemic stroke in China than in Europe and North America, but it is not clear whether this is due to underestimation. Our aim was to define the true frequency of AF-associated stroke, to determine the yield of 6-day Holter ECG to detect AF in Chinese stroke patients, and to elucidate predictors of newly detected AF.

Methods

Patients with acute ischemic stroke or transient ischemic attack (TIA) were enrolled in a prospective, multicenter cohort study of 6-day Holter monitoring within 7 days after stroke onset at 20 sites in China between 2013 and 2015. Independent predictors of newly-detected AF were determined by multivariate analysis.

Results

Among 1511 patients with ischemic stroke and TIA (mean age 63 years, 33.1% women), 305 (20.2%) had either previously known (196, 13.0%) or AF newly-detected by electrocardiography (53, 3.5%) or by 6-day Holter monitoring (56/1262, 4.4%). A history of heart failure (OR?=?4.70, 95%CI, 1.64–13.5), advanced age (OR?=?1.06, 95%CI, 1.04–1.09), NIHSS at admission (OR?=?1.06, 95%CI, 1.02–1.10), blood high density lipoprotein (HDL) (OR?=?1.52, 95%CI, 1.09–2.13), together with blood triglycerides (OR?=?0.64, 95%CI, 0.45–0.91) were independently associated with newly-detected AF.

Conclusions

Contrary to previous reports, AF-associated stroke is frequent (20%) in China if systemically sought. Prolonged noninvasive cardiac rhythm monitoring importantly increases AF detection in patients with recent ischemic stroke and TIA in China. Advanced age, history of heart failure, and higher admission NIHSS and higher level of HDL were independent indicators of newly-detected AF.

Trial registration

NCT02156765 (June 5, 2014).

     

Patient perspective on remote monitoring of cardiovascular implantable electronic devices: rationale and design of the REMOTE-CIED study

Background

Remote patient monitoring is a safe and effective alternative for the in-clinic follow-up of patients with cardiovascular implantable electronic devices (CIEDs). However, evidence on the patient perspective on remote monitoring is scarce and inconsistent.

Objectives

The primary objective of the REMOTE-CIED study is to evaluate the influence of remote patient monitoring versus in-clinic follow-up on patient-reported outcomes. Secondary objectives are to: 1) identify subgroups of patients who may not be satisfied with remote monitoring; and 2) investigate the cost-effectiveness of remote monitoring.

Methods

The REMOTE-CIED study is an international randomised controlled study that will include 900 consecutive heart failure patients implanted with an implantable cardioverter defibrillator (ICD) compatible with the Boston Scientific LATITUDE® Remote Patient Management system at participating centres in five European countries. Patients will be randomised to remote monitoring or in-clinic follow-up. The In-Clinic group will visit the outpatient clinic every 3–6 months, according to standard practice. The Remote Monitoring group only visits the outpatient clinic at 12 and 24 months post-implantation, other check-ups are performed remotely. Patients are asked to complete questionnaires at five time points during the 2-year follow-up.

Conclusion

The REMOTE-CIED study will provide insight into the patient perspective on remote monitoring in ICD patients, which could help to support patient-centred care in the future.     

A prospective controlled study: Minimally invasive stereotactic puncture therapy versus conventional craniotomy in the treatment of acute intracerebral hemorrhage

Background

Young stroke can have devastating consequences with respect to quality of life, the ability to work, plan or run a family, and participate in social life. Better insight into risk factors and the long-term prognosis is extremely important, especially in young stroke patients with a life expectancy of decades. To date, detailed information on risk factors and the long-term prognosis in young stroke patients, and more specific risk of mortality or recurrent vascular events, remains scarce.

Methods/Design

The FUTURE study is a prospective cohort study on risk factors and prognosis of young ischemic and hemorrhagic stroke among 1006 patients, aged 18-50 years, included in our study database between 1-1-1980 and 1-11-2010. Follow-up visits at our research centre take place from the end of 2009 until the end of 2011. Control subjects will be recruited among the patients' spouses, relatives or social environment. Information on mortality and incident vascular events will be retrieved via structured questionnaires. In addition, participants are invited to the research centre to undergo an extensive sub study including MRI.

Discussion

The FUTURE study has the potential to make an important contribution to increase the knowledge on risk factors and long-term prognosis in young stroke patients. Our study differs from previous studies by having a maximal follow-up of more than 30 years, including not only TIA and ischemic stroke but also hemorrhagic stroke, the addition of healthy controls and prospectively collect data during an extensive follow-up visit. Completion of the FUTURE study may provide better information for treating physicians and patients with respect to the prognosis of young stroke.     

Advance telephone calls ahead of reminder questionnaires increase response rate in non-responders compared to questionnaire reminders only: The RECORD phone trial

Background

Obstructive sleep apnea (OSA) and hypertension are well-known cardiovascular risk factors. Their control could reduce the burden of heart disease across populations. Several drugs are used to control hypertension, but the only consistently effective treatment of OSA is continuous positive airway pressure. The identification of a drug capable of improving OSA and hypertension simultaneously would provide a novel approach in the treatment of both diseases.

Methods/Design

This is a randomized double-blind clinical trial, comparing the use of chlorthalidone with amiloride versus amlodipine as a first drug option in patients older than 40 years of age with stage I hypertension (140 to 159/90 to 99 mmHg) and moderate OSA (15 to 30 apneas/hour of sleep). The primary outcomes are the variation of the number of apneas per hour and blood pressure measured by ambulatory blood pressure monitoring. The secondary outcomes are adverse events, somnolence scale (Epworth), ventilatory parameters and C reactive protein levels. The follow-up will last 8 weeks. There will be 29 participants per group. The project has been approved by the ethics committee of our institution.

Discussion

The role of fluid retention in OSA has been known for several decades. The use of diuretics are well established in treating hypertension but have never been appropriately tested for sleep apnea. As well as testing the efficacy of these drugs, this study will help to understand the mechanisms that link hypertension and sleep apnea and their treatment.

Trial registration

ClinicalTrials.gov: NCT01896661     

Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial

Background

Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients.

Methods

Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance.

Findings

On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections.

Interpretation

PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections.

Trial Registration

Controlled-Trials.com ISRCTN74386719     

Nurse-Led,Telephone-Based,Secondary Preventive Follow-Up after Stroke or Transient Ischemic Attack Improves Blood Pressure and LDL Cholesterol: Results from the First 12 Months of the Randomized,Controlled NAILED Stroke Risk Factor Trial

Background

Enhanced secondary preventive follow-up after stroke or transient ischemic attack (TIA) is necessary for improved adherence to recommendations regarding blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels. We investigated whether nurse-led, telephone-based follow-up was more efficient than usual care at improving BP and LDL-C levels at 12 months after hospital discharge.

Methods

We randomized 537 patients to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C measurements were performed at 1 month (baseline) and 12 months post-discharge. Intervention group patients who did not meet target values at baseline received additional follow-up, including titration of medication and lifestyle counselling, to reach treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L).

Results

At 12 months, mean systolic BP, diastolic BP and LDL-C was 3.3 (95% CI 0.3 to 6.3) mmHg, 2.3 mmHg (95% CI 0.5 to 4.2) and 0.3 mmol/L (95% CI 0.1 to 0.4) lower in the intervention group compared to controls. Among participants with values above the treatment goal at baseline, the difference in systolic BP and LDL-C was more pronounced (8.0 mmHg, 95% CI 4.0 to 12.1, and 0.6 mmol/L, 95% CI 0.4 to 0.9). A larger proportion of the intervention group reached the treatment goal for systolic BP (68.5 vs. 56.8%, p = 0.008) and LDL-C (69.7% vs. 50.4%, p < 0.001).

Conclusions

Nurse-led, telephone-based secondary preventive follow-up, including medication adjustment, was significantly more efficient than usual care at improving BP and LDL-C levels by 12 months post-discharge.

Trial Registration

ISRCTN Registry ISRCTN23868518     

Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED) trial: A multi-centre, double-masked, factorial randomised controlled trial

Background

Intravenous recombinant tissue plasminogen activator (rt-PA) is approved for use in selected patients with ischaemic stroke within 3 hours of symptom onset. IST-3 seeks to determine whether a wider range of patients may benefit.

Design

International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rt-PA in acute ischaemic stroke. Suitable patients must be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracerebral haemorrhage. With 1000 patients, the trial can detect a 7% absolute difference in the primary outcome. With3500 patients, it can detect a 4.0% absolute benefit & with 6000, (mostly treated between 3 & 6 hours), it can detect a 3% benefit.

Trial procedures

Patients are entered into the trial by telephoning a fast, secure computerised central randomisation system or via a secure web interface. Repeat brain imaging must be performed at 24–48 hours. The scans are reviewed 'blind' by expert readers. The primary measure of outcome is the proportion of patients alive and independent (Modified Rankin 0–2) at six months (assessed via a postal questionnaire mailed directly to the patient). Secondary outcomes include: events within 7 days (death, recurrent stroke, symptomatic intracranial haemorrhage), outcome at six months (death, functional status, EuroQol).

Trial registration

ISRCTN25765518     

Multidisciplinary transmural rehabilitation for older persons with a stroke: the design of a randomised controlled trial

Background

Stroke is one of the major causes of loss of independence, decreased quality of life and mortality among elderly people. About half of the elderly stroke patients discharged after rehabilitation in a nursing home still experience serious impairments in daily functioning one year post stroke, which can lead to difficulties in picking up and managing their social life. The aim of this study is to evaluate the effectiveness and feasibility of a new multidisciplinary transmural rehabilitation programme for older stroke patients.

Methods

A two group multicentre randomised controlled trial is used to evaluate the effects of the rehabilitation programme. The programme consists of three care modules: 1) neurorehabilitation treatment for elderly stroke patients; 2) empowerment training for patient and informal caregiver; and 3) stroke education for patient and informal caregiver. The total programme has a duration of between two and six months, depending on the individual problems of the patient and informal caregiver. The control group receives usual care in the nursing home and after discharge.Patients aged 65 years and over are eligible for study participation when they are admitted to a geriatric rehabilitation unit in a nursing home due to a recent stroke and are expected to be able to return to their original home environment after discharge. Data are gathered by face-to-face interviews, self-administered questionnaires, focus groups and registration forms. Primary outcomes for patients are activity level after stroke, functional dependence, perceived quality of life and social participation. Outcomes for informal caregivers are perceived care burden, objective care burden, quality of life and perceived health. Outcome measures of the process evaluation are implementation fidelity, programme deliverance and the opinion of the stroke professionals, patients and informal caregivers about the programme. Outcome measures of the economic evaluation are the healthcare utilisation and associated costs. Data are collected at baseline, and after six and 12 months. The first results of the study will be expected in 2014.

Trial registration

International Standard Randomised Controlled Trial Register Number ISRCTN62286281, The Dutch Trial Register NTR2412

     

Randomized placebo-controlled trial on azithromycin to reduce the morbidity of bronchiolitis in Indigenous Australian infants: rationale and protocol

Background

Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux.

Methods/design

The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study.

Discussion

The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol.

Trial registration number

ClinicalTrials (NCT): NCT01031667     

Cellular versus acellular matrix devices in treatment of diabetic foot ulcers: study protocol for a comparative efficacy randomized controlled trial

Background

The referral letter plays a key role both in the communication between primary and secondary care, and in the quality of the health care process. Many studies have attempted to evaluate and improve the quality of these referral letters, but few have assessed the impact of their quality on the health care delivered to each patient.

Methods

A cluster randomized trial, with the general practitioner office as the unit of randomization, has been designed to evaluate the effect of a referral intervention on the quality of health care delivered. Referral templates have been developed covering four diagnostic groups: dyspepsia, suspected colonic malignancy, chest pain, and chronic obstructive pulmonary disease. Of the 14 general practitioner offices primarily served by University Hospital of North Norway Harstad, seven were randomized to the intervention group. The primary outcome is a collated quality indicator score developed for each diagnostic group. Secondary outcomes include: quality of the referral, health process outcome such as waiting times, and adequacy of prioritization. In addition, information on patient satisfaction will be collected using self-report questionnaires. Outcome data will be collected on the individual level and analyzed by random effects linear regression.

Discussion

Poor communication between primary and secondary care can lead to inappropriate investigations and erroneous prioritization. This study’s primary hypothesis is that the use of a referral template in this communication will lead to a measurable increase in the quality of health care delivered.

Trial registration

This trial has been registered at ClinicalTrials.gov. The trial registration number is NCT01470963     

Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE): a randomized controlled trial protocol

Background

Residual disability after stroke is substantial; 65% of patients at 6 months are unable to incorporate the impaired upper extremity into daily activities. Task-oriented training programs are rapidly being adopted into clinical practice. In the absence of any consensus on the essential elements or dose of task-specific training, an urgent need exists for a well-designed trial to determine the effectiveness of a specific multidimensional task-based program governed by a comprehensive set of evidence-based principles. The Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) Stroke Initiative is a parallel group, three-arm, single blind, superiority randomized controlled trial of a theoretically-defensible, upper extremity rehabilitation program provided in the outpatient setting. The primary objective of ICARE is to determine if there is a greater improvement in arm and hand recovery one year after randomization in participants receiving a structured training program termed Accelerated Skill Acquisition Program (ASAP), compared to participants receiving usual and customary therapy of an equivalent dose (DEUCC). Two secondary objectives are to compare ASAP to a true (active monitoring only) usual and customary (UCC) therapy group and to compare DEUCC and UCC.

Methods/design

Following baseline assessment, participants are randomized by site, stratified for stroke duration and motor severity. 360 adults will be randomized, 14 to 106 days following ischemic or hemorrhagic stroke onset, with mild to moderate upper extremity impairment, recruited at sites in Atlanta, Los Angeles and Washington, D.C. The Wolf Motor Function Test (WMFT) time score is the primary outcome at 1 year post-randomization. The Stroke Impact Scale (SIS) hand domain is a secondary outcome measure. The design includes concealed allocation during recruitment, screening and baseline, blinded outcome assessment and intention to treat analyses. Our primary hypothesis is that the improvement in log-transformed WMFT time will be greater for the ASAP than the DEUCC group. This pre-planned hypothesis will be tested at a significance level of 0.05.

Discussion

ICARE will test whether ASAP is superior to the same number of hours of usual therapy. Pre-specified secondary analyses will test whether 30 hours of usual therapy is superior to current usual and customary therapy not controlled for dose.

Trial registration

http://www.ClinicalTrials.gov Identifier: NCT00871715