Teresa Melody

Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial)

IntroductionSeveral observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis.MethodsA single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization.Results100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238).ConclusionsAcute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings.Trial RegistrationInternational Standard Randomized Control Trial Registry ISRCTN64637517.

Cerebral Oximetry During Cardiac Arrest: A Multicenter Study of Neurologic Outcomes and Survival.

Objectives: Cardiac arrest is associated with morbidity and mortality because of cerebral ischemia. Therefore, we tested the hypothesis that higher regional cerebral oxygenation during resuscitation is associated with improved return of spontaneous circulation, survival, and neurologic outcomes at hospital discharge. We further examined the validity of regional cerebral oxygenation as a test to predict these outcomes. Design: Multicenter prospective study of in-hospital cardiac arrest. Setting: Five medical centers in the United States and the United Kingdom. Patients: Inclusion criteria are as follows: in-hospital cardiac arrest, age 18 years old or older, and prolonged cardiopulmonary resuscitation greater than or equal to 5 minutes. Patients were recruited consecutively during working hours between August 2011 and September 2014. Survival with a favorable neurologic outcome was defined as a cerebral performance category 1–2. Interventions: Cerebral oximetry monitoring. Measurements and Main Results: Among 504 in-hospital cardiac arrest events, 183 (36%) met inclusion criteria. Overall, 62 of 183 (33.9%) achieved return of spontaneous circulation, whereas 13 of 183 (7.1%) achieved cerebral performance category 1–2 at discharge. Higher mean ± SD regional cerebral oxygenation was associated with return of spontaneous circulation versus no return of spontaneous circulation (51.8% ± 11.2% vs 40.9% ± 12.3%) and cerebral performance category 1–2 versus cerebral performance category 3–5 (56.1% ± 10.0% vs 43.8% ± 12.8%) (both p < 0.001). Mean regional cerebral oxygenation during the last 5 minutes of cardiopulmonary resuscitation best predicted the return of spontaneous circulation (area under the curve, 0.76; 95% CI, 0.69–0.83); regional cerebral oxygenation greater than or equal to 25% provided 100% sensitivity (95% CI, 94–100) and 100% negative predictive value (95% CI, 79–100); regional cerebral oxygenation greater than or equal to 65% provided 99% specificity (95% CI, 95–100) and 93% positive predictive value (95% CI, 66–100) for return of spontaneous circulation. Time with regional cerebral oxygenation greater than 50% during cardiopulmonary resuscitation best predicted cerebral performance category 1–2 (area under the curve, 0.79; 95% CI, 0.70–0.88). Specifically, greater than or equal to 60% cardiopulmonary resuscitation time with regional cerebral oxygenation greater than 50% provided 77% sensitivity (95% CI,:46–95), 72% specificity (95% CI, 65–79), and 98% negative predictive value (95% CI, 93–100) for cerebral performance category 1–2. Conclusions: Cerebral oximetry allows real-time, noninvasive cerebral oxygenation monitoring during cardiopulmonary resuscitation. Higher cerebral oxygenation during cardiopulmonary resuscitation is associated with return of spontaneous circulation and neurologically favorable survival to hospital discharge. Achieving higher regional cerebral oxygenation during resuscitation may optimize the chances of cardiac arrest favorable outcomes.

An evaluation of three methods of in-hospital cardiac arrest educational debriefing: The cardiopulmonary resuscitation debriefing study

BACKGROUND The use of cardiac arrest educational debriefing has been associated with improvements in cardiopulmonary resuscitation (CPR) quality and patient outcome. The practical challenges associated with delivering some debriefing approaches may not be generalisable to the UK health setting. The aim of this study was to evaluate the deliverability and effectiveness of three cardiac arrest debriefing approaches that were tailored to UK working practice. METHODS We undertook a before/after study at three hospital sites. During the post-intervention period of the study, three cardiac arrest educational debriefing models were implemented at study hospitals (one model per hospital). To evaluate the effectiveness of the interventions, CPR quality and patient outcome data were collected from consecutive adult cardiac arrest events attended by the hospital cardiac arrest team. The primary outcome was chest compression depth. RESULTS Between November 2011 and July 2014, 1198 cardiac arrest events were eligible for study inclusion (782 pre-intervention; 416 post-intervention). The quality of CPR was high at baseline. During the post-intervention period, cardiac arrest debriefing interventions were delivered to 191 clinicians on 344 occasions. Debriefing interventions were deliverable in practice, but were not associated with a clinically important improvement in CPR quality. The interventions had no effect on patient outcome. CONCLUSION The delivery of these cardiac arrest educational debriefing strategies was feasible, but did not have a large effect on CPR quality. This may be attributable to the high-quality of CPR being delivered in study hospitals at baseline. TRIAL REGISTRATION ISRCTN39758339.

Randomised controlled pilot study to investigate the effectiveness of thoracic epidural and paravertebral blockade in reducing chronic post-thoracotomy pain: TOPIC feasibility study protocol

Introduction Open chest surgery (thoracotomy) is considered the most painful of surgical procedures. Forceful wound retraction, costochondral dislocation, posterior costovertebral ligament disruption, intercostal nerve trauma and wound movement during respiration combine to produce an acute, severe postoperative pain insult and persistent chronic pain many months after surgery is common. Three recent systematic reviews conclude that unilateral continuous paravertebral blockade (PVB) provides analgesia at least equivalent to thoracic epidural blockade (TEB) in the postoperative period, has a lower failure rate, and symptom relief that lasted months. Crucially, PVB may reduce the development of subsequent chronic pain by intercostal nerve protection or decreased nociceptive input. The overall aim is to determine in patients who undergo thoracotomy whether perioperative PVB results in reducing chronic post-thoracotomy pain (CPTP) compared with TEB. This pilot study will evaluate feasibility of a substantive trial. Methods and analysis TOPIC is a randomised controlled trial comparing the effectiveness of TEB and PVB in reducing CPTP. This is a pilot study to evaluate feasibility of a substantive trial and study processes in 2 adult thoracic centres, Heart of England NHS Foundation Trust (HEFT) and University Hospital of South Manchester NHS Foundation Trust (UHSM). The primary objective is to establish the number of patients randomised as a proportion of those eligible. Secondary objectives include evaluation of study processes. Analyses of feasibility and patient-reported outcomes will primarily take the form of simple descriptive statistics and where appropriate, point estimates of effects sizes and associated 95% CIs. Ethics and dissemination The study has obtained ethical approval from NHS Research Ethics Committee (REC number 14/EM/1280). Dissemination plan includes: informing patients and health professionals; engaging multidisciplinary professionals to support a proposal of a definitive trial and submission for a full HTA application dependent on the success of the study. Trial registration number ISRCTN45041624; Pre-results.

The role of imams and mosques in health promotion in Western societies—a systematic review protocol

BackgroundMuslims comprise 4.8% of the national population in the UK and also form a significant proportion of its ethnic minority population, with trends set to continue for the foreseeable future. With ethnic minority health inequalities deepening further, there is an apparent lack of strategies to effectively tackle this growing problem. Imams, Muslim religious leaders, represent a hitherto under-investigated group who may have the capacity to facilitate positive health change within Muslim communities. The aim of this systematic review is to investigate the role of imams and mosques in health promotion in Muslim communities residing in Western societies.MethodWe will undertake a systematic literature review of PubMed, CINAHL, EMBASE, MEDLINE, the Cochrane Library (CENTRAL) Register, NICE Evidence and Google Scholar. Eligible studies will primarily assess the role of imams and mosques in health promotion in Western societies. Secondary objectives include the identification of how mosque-based and imam-supported interventions were organised and delivered, and to explore which, if any, subgroups within the Western Muslim communities are more responsive to such interventions. Two independent reviewers will screen references from the electronic literature searches for eligible studies. The following data will be extracted to populate a tabulated form: study design, location of study, time of study, participant demographics, description of intervention, outcome measures of individual study, analysis methods, religious content (imams, mosques, religious denomination), outcomes and conclusions of study. Two investigators will independently assess the methodological quality of included studies. A narrative synthesis approach will be employed to analyse the extracted data in order to explore the role of imams and mosques in health promotion in Western settings.DiscussionThis systematic review will elucidate the role and effectiveness of imams and mosques in health promotion in Western societies. If the use of imams and mosques is shown to be effective, this will encourage further research in Western Muslim communities that effectively utilise imams and mosques as part of novel strategies and interventions for health promotion in this group. The review will also aid policy makers in Western societies with a view to tackling and potentially reversing the problem of increasing ethnic minority health inequality.Systematic review registrationPROSPERO (CRD42015020166)

Comparison of regional with general anaesthesia on postoperative delirium (RAGA-delirium) in the older patients undergoing hip fracture surgery: study protocol for a multicentre randomised controlled trial

Introduction Postoperative delirium (POD) is a common serious postoperative complication especially in older people and is associated with increased mortality, morbidity and healthcare costs. There is no clear consensus which anaesthesia is associated with less incidence of POD for older patients. We aim to assess whether regional anaesthesia results in lower incidence of POD comparing with general anaesthesia (GA) among older patients undergoing hip fracture surgery. Methods and analysis RAGA-delirium is a pragmatic, multicentre, prospective, parallel grouped, randomised controlled clinical trial comparing RA or GA for hip fracture surgery. A total of 1000 patients who are 65 years or over and who are having planned hip fracture surgery in nine clinical trial centres of China will be randomised in a 1:1 ratio to receive either anaesthesia for the surgery. The primary endpoint will be the incidence of POD at day 7. The secondary endpoints will be the subtype, severity and duration of delirium, postoperative acute pain score, incidence of other postoperative non-delirium complications, quality of life and cost-effective outcomes. Randomisation will be performed at the patient level using computer-generated assignment. Outcome assessors will be blinded from intervention assignment. Assessments will be conducted before surgery, intraoperatively, postoperatively, during the hospital stay, at 30-day, 6-month and 1-year postoperative intervals. Potential impact of study This study will provide clinical evidence with a more robust methodology to help anaesthetists in selecting appropriate anaesthesia for older patients with high risk for POD. At the era of increasing emphasis on delirium prevention, this trial has the potential to inform the future national guideline to reduce POD. Ethics and dissemination Ethical approved by the local institutional review board. Trial results will be presented at national and international academic conferences, and published in peer-reviewed journals. Trial registration number ClinicalTrials.gov (NCT02213380); pre-results.

Embedding patient and public involvement within research – How to set up a research patient ambassador group within a NHS trust

Patient and public involvement in clinical research is vital to ensure the correct research questions are being asked to address patient and public’s needs. Patient and public involvement groups can be set up within individual research departments and local NHS trusts to help guide researchers, but there is a lack of guidance on how to develop and implement patient and public involvement groups. In this paper, we discuss the vital role and benefits of patient and public involvement in clinical research. We also describe how a research patient ambassador group called the Clinical Research Ambassador Group was created at the Heart of England NHS Foundation Trust to offer some advice and guidance for researchers and clinicians wishing to form their own group within a NHS trust.

The Use of Beta 2-Agonists for the Treatment of Acute Respiratory Distress Syndrome:

The clinical problem Acute respiratory distress syndrome (ARDS) remains a significant problem in intensive care, occurring in 14% of mechanically ventilated patients 1 and associated with a mortality of 25-40%, and a substantial reduction in survivors’ quality of life. 2 A recent ARDS definition taskforce has proposed a new classification based on degree of hypoxaemia, classifying ARDS as mild (PaO2/FiO2 200-300 mm Hg (26.6-40 kPa), moderate (PaO2/FiO2 100-200 mm Hg (13.326.6 kPa)) or severe (PaO2/FiO2 <100 mm Hg (13.3 kPa)). This has been named the Berlin Definition and has demonstrated improved predictive validity for mortality compared to the previous American-European Consensus Conference definition from 1994. 3 β2-agonists could be a potential pharmacological intervention because they act on the many pulmonary cellular pathways thought to be associated with the pathophysiology of ARDS. These drugs reduce neutrophil sequestration, activation, and production of inflammatory cytokines, and activate β2-receptors on alveolar type-1 and type-2 cells, which increases intracellular cyclic adenosine monophosphate, leading to increased sodium transport and acceleration of alveolar fluid reabsorption. 4 Evidence for change The BALTI-1 trial,5 a single-centre, randomised controlled trial in 40 patients with ARDS (PaO2/FiO2 <300 mm Hg (40 kPa)) treated with intravenous salbutamol, showed that an infusion of salbutamol for seven days caused significant reductions in extravascular lung water and plateau airway pressure. The BALTI-2 study,6 a phase-3 randomised trial of intravenous salbutamol for ARDS was halted by the Data Monitoring and Ethics Committee due to safety concerns. The final analyses found excess 28-day mortality in the salbutamol treated group – 55 (34%) of 161 patients died in the salbutamol group vs 38 (23%) of 163 in the placebo group; risk ratio (RR) 1·47, 95% CI 1·03-2·08. Number needed to harm (NNH) was 9.2 (95% CI 4.9-100.9). The study drug was stopped prematurely more often in the salbutamol arm than placebo arm for reasons of tachycardia (14.3% vs 1.2%), new-onset arrhythmia (8.7% vs 1.8%) and new-onset lactic acidosis (6.2% vs 0.6%). Post hoc analysis of cause of death was performed for the 55 patients in the salbutamol arm and 38 patients in the placebo arm who died, to determine any impact of these cardiovascular events. This showed no difference in the primary cause of death attributed to a cardiovascular cause (1.8% vs 2.6%) but when looking at co-morbidity contributing to death, cardiovascular disease was listed for 12 patients (21.8%) in the salbutamol group and two patients (5.3%) in the placebo group (p=0.04). The nebulised route was examined in the ALTA trial.