Elaine Beller

A is for aphorism: If many treatments are used for a disease, all are insufficient

Georga Cooke et al. — Wed, 30 Jan 2013 15:15:34 PST

Extract:
The aphorism, ‘If many treatments are used for a disease, all are insufficient’ seems self evident. If any treatments were beneficial (‘sufficient’ in the aphorism), there would be no need to search for new treatments and therefore the presence of many available treatments might be a marker for none of
them being effective. We decided to test this aphorism by establishing a set of conditions for which there are treatments classified by evidence of effectiveness. Clinical Evidence, from the British Medical Journal’s stable of publications, seemed to fit the bill well. It is a database of evidence based systematic overviews of the benefits and harms of treatments for many of the conditions encountered in primary care, using a transparent process of determining the level of evidence for each.

Addressing antibiotic resistance: Focusing on acute respiratory infections in primary care

Chris Del Mar et al. — Wed, 30 Jan 2013 15:00:26 PST

Extract:
We have been aware for decades – perhaps as a somewhat far-off theoretical problem – that antibiotic resistance is a threat to healthcare worldwide. However, the crisis is now here and very real. Each year in Europe alone, 25,000 deaths are directly attributed to antibiotic resistance. New antibiotics are not being produced fast enough, and resistance means we are running out of antibiotics of last resort.

Contemporary results following surgical repair of acute type A aortic dissection (AAAD): A single centre experience

Andrew J. M. Campbell-Lloyd et al. — Wed, 21 Dec 2011 17:03:37 PST

Objectives: The study aims to define predictors of neurological dysfunction, 30-day mortality, long-term survival and quality of life following repair of acute type A aortic dissection (AAAD).

Methods: Between 2000 and 2008, 65 patients underwent repair of AAAD. Sixty-four pre-, intra- and post-operative variables were studied. Mean follow-up was 26.6 months.

Results: The mean age was 61years; 60% were male and five had Marfan's syndrome. At presentation, ischaemic ECG changes were seen in 45%, malperfusion syndrome in 59%, moderate–severe aortic regurgitation in 48% and tamponade in 16%. EF was <40% in 17%. There was a delay of >12hours between diagnosis and operation in 64%. Axillary cannulation was performed in 37%. Cerebral protection was by hypothermic arrest (HCA) alone (19%), HCA with retrograde cerebral perfusion (RCP) (11%), or HCA with antegrade cerebral perfusion (ACP) (46%). The procedure was performed on cross-clamp in 24%. Full arch replacement was performed in 14% and concomitant coronary artery grafting was performed in 11%. Post-operative neurological dysfunction was present in 33.8%. The only significant predictor of poor neurological outcome was full arch replacement (p=0.04) on univariate analysis. In-hospital OR 30 mortality was 23.53%. Significant predictors of mortality were low ejection fraction (p=0.017) and post-operative renal failure (p=0.012). Long-term survival was 70% at two years, 50% at five years and 25% at nine years. Functional outcomes and long-term quality of life were assessed in 69% of patients who were alive at last follow-up. Ninety percent of patients reported minimal limitation on functional scores. Quality of life was assessed using the EQ-5D questionnaire. Forty-eight percent of patients recorded full health with an overall mean index of 0.854 (where the best possible score is 1) using the US preference weighted index score.

Cardiac surgery in the presence of dialysis: Effect on mid-term outcomes and quality of life

Hasanga Jayasekera et al. — Tue, 20 Dec 2011 22:20:01 PST

Background: This study evaluates the impact on short and mid-term outcomes and quality of life of dialysis dependent patients undergoing cardiac surgery. The benefit to patients from a bio-psycho-social perspective is put into context via an inter-personal patient interview.

Methods: The study period was from February 1999 to February 2009. Data on 45 dialysis dependent patients undergoing cardiac surgery was prospectively collected and analysed retrospectively. The mean age was 59.9 years and sex ratio (M:F) of 32:13. All patients were New York Heart Association (NYHA) class >2 preoperatively. Fifty-five percent (25/45) of these patients had coronary artery bypass graft surgery (CABG) and 28% (12/45) aortic valve replacement surgery alone. Forty-two variables were studied to define predictors of outcome. Follow-up was 100% (18/18) with a mean follow-up time of 48.1 months (0–124 months). They were followed up with quality of life and functional coping score surveys (SF-36).

Results: The main postoperative morbidities were pulmonary complications 20% (9/45), multi-organ failure 11%(5/45) and blood transfusion rates 40% (18/45). The 30 day mortality of the dialysis patients was 13.3% (6/45) and late death was 54% (21/39). Increasing age, pulmonary complications and blood product usage were the significant predictors of both 30 day mortality (age: p = 0.02, pulmonary: p = 0.003, blood product usage: p = 0.03) and late death (age: p = 0.008, pulmonary: p = 0.02, blood product usage: p = 0.02). New York Heart Association class was I–II in 83% (15/18) on long term follow up.All five patients awaiting renal transplants received their transplant in the first six months post-operatively. The overall survival at one year was 78% and five years was 40%. On SF-36 health questionnaire all patients scored less on physical functioning than the Australian norms (24.89±4.10).

Conclusions: Cardiac surgery in the presence of renal failure is associated with significant morbidity and mortality. The overall survival and quality of life of dialysis patients undergoing cardiac surgery is poor.

The impact of extended-hours home hemodialysis and buttonhole cannulation technique on hospitalization rates for septic events related to dialysis access

Carolyn Van Eps et al. — Thu, 15 Dec 2011 17:40:02 PST

Few studies adequately document adverse events in patients receiving long, slow, and overnight hemodialysis (NHD). Concerns about high rates of dialysis access complications have been raised. This is an observational cohort study comparing hospital admission rates for vascular access complications between alternate nightly NHD (n=63) and conventional hemodialysis (n=172) patients established on chronic hemodialysis for at least 3 months. Overall, hospital admission rates and hospital admission rates for cardiac and all infective events are also reported. The NHD cohort was younger and less likely to be female, diabetic, or have ischemic heart disease than the conventional hemodialysis cohort. When NHD and buttonhole cannulation technique were used simultaneously, there was a demonstrated increased risk of septic dialysis access events: incidence rate ratio 3.0 (95% confidence interval 1.04–8.66) (P=0.04). The majority of blood culture isolates in NHD patients were gram-positive organisms, particularly Staphylococcus aureus. Alternate nightly NHD did not significantly change total hospital admissions or hospital admissions for indications other than dialysis access complications, compared with conventional hemodialysis. Our data suggest that buttonhole cannulation technique should be used with caution in patients performing extended-hours hemodialysis as this combination appears to increase the risk of septic access complications. Randomized-controlled trials are needed to confirm these findings.

Physical function and health-related quality of life of older adults undergoing hospital rehabilitation: How strong is the association?

Steven McPhail et al. — Thu, 15 Dec 2011 16:52:23 PST

Extract:

To the Editor: When an elderly patient has a first-time presentation of psychiatric symptoms, a physical cause should be suspected. In geriatric practice, these symptoms are often due to delirium, cognitive decline, or a mood disorder. The present case history illustrates the importance of further investigation when geriatric assessment alone cannot explain the symptoms sufficiently.

Reference bias: Presentation of extreme health states prior to EQ-VAS improves health-related quality of life scores. A randomised cross-over trial

Steven McPhail et al. — Thu, 15 Dec 2011 16:52:21 PST

Background - Clinical practice and clinical research has made a concerted effort to move beyond the use of clinical indicators alone and embrace patient focused care through the use of patient reported outcomes such as health-related quality of life. However, unless patients give consistent consideration to the health states that give meaning to measurement scales used to evaluate these constructs, longitudinal comparison of these measures may be invalid. This study aimed to investigate whether patients give consideration to a standard health state rating scale (EQ-VAS) and whether consideration of good and poor health state descriptors immediately changes their self-report.

Methods - A randomised crossover trial was implemented amongst hospitalised older adults (n = 151). Patients were asked to consider descriptions of extremely good (Description-A) and poor (Description-B) health states. The EQ-VAS was administered as a self-report at baseline, after the first descriptors (A or B), then again after the remaining descriptors (B or A respectively). At baseline patients were also asked if they had considered either EQ-VAS anchors.

Results - Overall 106/151 (70%) participants changed their self-evaluation by ≥5 points on the 100 point VAS, with a mean (SD) change of +4.5 (12) points (p < 0.001). A total of 74/151 (49%) participants did not consider the best health VAS anchor, of the 77 who did 59 (77%) thought the good health descriptors were more extreme (better) then they had previously considered. Similarly 85/151 (66%) participants did not consider the worst health anchor of the 66 who did 63 (95%) thought the poor health descriptors were more extreme (worse) then they had previously considered.

Conclusions - Health state self-reports may not be well considered. An immediate significant shift in response can be elicited by exposure to a mere description of an extreme health state despite no actual change in underlying health state occurring. Caution should be exercised in research and clinical settings when interpreting subjective patient reported outcomes that are dependent on brief anchors for meaning.

Trial Registration - Australian and New Zealand Clinical Trials Registry (#ACTRN12607000606482) http://www.anzctr.org.au webcite

Cost-effectiveness of lowering blood pressure with a fixed combination of perindopril and indapamide in type 2 diabetes mellitus: An ADVANCE trial-based analysis

Paul Glasziou et al. — Thu, 20 Jan 2011 17:35:05 PST

Objective: To determine the cost-effectiveness of routine administration, irrespective of blood pressure (BP), of a fixed-dose combination of perindopril and indapamide to patients with type 2 diabetes mellitus.

Design, setting and participants: Prospective cost-effectiveness analysis within the Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trial, an international, multicentre, randomised controlled trial of 11 140 participants with type 2 diabetes randomly allocated to receive perindopril plus indapamide (4mg-1.25mg/day) or placebo.

Main outcome measures: Health-related quality-of-life measured by the EuroQol-5D, resource utilisation, and cost-effectiveness (cost per death averted at 4.3 years' average follow-up, and estimated cost per life-year gained, by extrapolation).

Results: The mean health-related quality-of-life score of survivors was 0.80 (on a 0-1 scale [death to full health]), with no difference between treatment groups. Active treatment reduced hospital admissions for coronary heart disease and coronary revascularisation by 5%. For the Australian participants, perindopril-indapamide cost A$1368 per patient during the trial period, but reduced total hospitalisation costs by A$410 and other medication costs (mainly other BP-lowering drugs) by A$332. The absolute reduction in all-cause mortality for the active treatment group was 1.1%, giving a cost per life saved of A$49 200. Lifetime extrapolation gave an estimated cost per life-year saved of A$10 040 (discounted at 5% per year).

Conclusion: The combination of perindopril and indapamide in patients with type 2 diabetes appears to be cost-effective.

Trial registration: United States National Library of Medicine NCT00145925.

The Honeypot study protocol: A randomised controlled trial of exit site application of Medihoney antibacterial wound gel for the prevention of catheter-associated infections in peritoneal dialysis patients

David W. Johnson et al. — Tue, 27 Jul 2010 17:02:43 PDT

Objectives: The primary objective of this study is to determine whether daily exit-site application of standardized antibacterial honey (Medihoney Antibacterial Wound Gel; Comvita, Te Puke, New Zealand) results in a reduced risk of catheter-associated infections in peritoneal dialysis (PD) patients compared with standard topical mupirocin prophylaxis of nasal staphylococcal carriers.

Design: Multicenter, prospective, open label, randomized controlled trial.

Setting: PD units throughout Australia and New Zealand.

Participants: The study will include both incident and prevalent PD patients (adults and children) for whom informed consent can be provided. Patients will be excluded if they have had (1) a history of psychological illness or condition that interferes with their ability to understand or comply with the requirements of the study; (2) recent (within 1 month) exit-site infection, peritonitis, or tunnel infection; (3) known hypersensitivity to, or intolerance of, honey or mupirocin; (4) current or recent (within 4 weeks) treatment with an antibiotic administered by any route; or (5) nasal carriage of mupirocin-resistant Staphylococcus aureus.

Methods: 370 subjects will be randomized 1:1 to receive either daily topical exit-site application of Medihoney Antibacterial Wound Gel (all patients) or nasal application of mupirocin if staphylococcal nasal carriage is demonstrated. All patients in the control and intervention groups will perform their usual exit-site care according to local practice. The study will continue until 12 months after the last patient is recruited (anticipated recruitment time is 24 months).

Main Outcome Measures: The primary outcome measure will be time to first episode of exit-site infection, tunnel infection, or peritonitis, whichever comes first. Secondary outcome measures will include time to first exit-site infection, time to first tunnel infection, time to first peritonitis, time to infection-associated catheter removal, catheter-associated infection rates, causative organisms, incidence of mupirocin-resistant microbial isolates, and other adverse reactions.

Conclusions: This multicenter Australian and New Zealand study has been designed to provide evidence to help nephrologists and their PD patients determine the optimal strategy for preventing PD catheter-associated infections. Demonstration of a significant improvement in PD catheter-associated infections with topical Medihoney will provide clinicians with an important new prophylactic strategy with a low propensity for promoting antimicrobial resistance.

Preventing AVF thrombosis: The rationale and design of the omega-3 fatty acids (fish oils) and aspirin in vascular access outcomes in renal disease (FAVOURED) study

Ashley Irish et al. — Tue, 27 Jul 2010 16:25:13 PDT

Background: Haemodialysis (HD) is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF). The primary failure rate of an AVF ranges between 20–54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s) for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF.

Methods/Design: The study population is adult patients with stage IV or V chronic kidney disease (CKD) currently on HD or where HD is planned to start within 6 months in whom a planned upper or lower arm AVF is to be the primary HD access. Using a factorial-design trial, patients will be randomised to aspirin or matching placebo, and also to omega-3 fatty acids or matching placebo, resulting in four treatment groups (aspirin placebo/omega-3 fatty acid placebo, aspirin/omega-3 fatty acid placebo, aspirin placebo/omega-3 fatty acid, aspirin/omega-3 fatty acid). Randomisation will be achieved using a dynamic balancing method over the two stratification factors of study site and upper versus lower arm AVF. The medication will be commenced pre-operatively and continued for 3 months post surgery. The primary outcome is patency of the AVF at three months after randomisation. Secondary outcome measures will include functional patency at six and twelve months, primary patency time, secondary (assisted) patency time, and adverse events, particularly bleeding.

Discussion: This multicentre Australian and New Zealand study has been designed to determine whether the outcome of surgery to create de novo AVF can be improved by the use of aspirin and/ or omega-3 fatty acids. Recently a placebo-controlled trial has shown that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Our study presents significant differences in the anti-platelet agents used, the study design, and surgical and patient demographics that should contribute further evidence regarding the efficacy of antiplatelet agents.

Trial Registration: Australia & New Zealand Clinical Trials Register (ACTRN12607000569404).

Two perspectives of proxy reporting of health-related quality of life using the EQ-5D: An investigation of agreement

Steven McPhail et al. — Tue, 27 Jul 2010 15:56:42 PDT

Background: Proxy-reporting has been proposed as an alternative to self-report of health-related quality of life (HRQoL) for patients with poor cognition. There are 2 possible perspectives from which to complete a proxy-report, answer as the patient would (proxy-patient) or from the proxy's own perspective (proxy-proxy). Most research has not differentiated between perspectives. Agreement between patient and proxy-reports from either perspective has not been investigated using the Euroqol-5D (EQ-5D) among elderly hospital patients undergoing rehabilitation.

Objectives: Identify agreement levels between proxy-patient and patient self-report as well as proxy-proxy and patient self-report of the EQ-5D and investigate interaction effects of timing (admission vs. discharge) and basic cognition (intact vs. not intact).

Research Design: Repeated measures, inter-rater agreement investigation of clinician proxy-report, and patient self-report incorporating; proxy-patient reports (perspective A) and proxy-proxy reports (perspective B).

Subjects: Geriatric rehabilitation patients (n = 272) and their proxies (treating physiotherapists n = 29).

Measures: EQ-5D for HRQoL and Mini Mental State Examination for cognition.

Results: One hundred fifty (89%) proxy-patient and 130 (98%) proxy-proxy datasets were complete, 51 perspective A and 52 perspective B patients did not have basic cognition intact. Proxy-patient assessments had strong agreement with self-report at discharge across all cognition levels (kappa = 0.76-0.95), but at admission had stronger agreement among patients with better cognition (kappa = 0.70-0.86) than patients with lower cognition (kappa = 0.47-0.76). At admission and discharge proxy-proxy assessments generally had moderate agreement with self-report among patients with poor cognition on most domains with proxies giving lower scores than patients (kappa = 0.23-0.81), this is in contrast to proxy-proxy assessments and patients with better cognition (kappa = 0.55-0.95).

Conclusions: Clinician (physiotherapist) proxy-reports among this population generally had good agreement with patient self-report though this was affected by proxy perspective, patient cognition, and timing.