A prospective clinical trial of a real-time polymerase chain reaction assay for the diagnosis of candidemia in nonneutropenic, critically ill adults

Background. Invasive Candida infection among nonneutropenic, critically ill adults is a clinical problem that has received increasing attention in recent years. Poor performance of extant diagnostic modalities has promoted risk-based, preemptive prescribing in view of the poor outcomes associated with inadequate or delayed antifungal therapy; this risks unnecessary overtreatment. A rapid, reliable diagnostic test could have a substantial impact on therapeutic practice in this patient population.

Methods. Three TaqMan-based real-time polymerase chain reaction assays were developed that are capable of detecting the main medically important Candida species, categorized according to the likelihood of fluconazole susceptibility. Assay 1 detected Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida dubliniensis. Assays 2 and 3 detected Candida glabrata and Candida krusei, respectively. The clinical performance of these assays, applied to serum, was evaluated in a prospective trial of nonneutropenic adults in a single intensive care unit.

Results. In all, 527 specimens were obtained from 157 participants. All 3 assays were run in parallel for each specimen; they could be completed within 1 working day. Of these, 23 specimens were obtained from 23 participants categorized as having proven Candida infection at the time of sampling. If a single episode of Candida famata candidemia was excluded, the estimated clinical sensitivity, specificity, and positive and negative predictive values of the assays in this trial were 90.9%, 100%, 100% and 99.8%, respectively.

Conclusions. These data suggest that the described assays perform well in this population for enhancing the diagnosis of candidemia. The extent to which they may affect clinical outcomes, prescribing practice, and cost-effectiveness of care remains to be ascertained.

Peer-mentoring for first-time mothers from areas of socio-economic disadvantage: a qualitative study within a randomised controlled trial

Objective: To explore the difficulties experienced by lay-workers, women and health professionals involved in a peer-mentoring programme for first-time mothers living in socially disadvantaged areas. Design: Qualitative study; semi-structured interviews with lay-worker peer-mentoring programme participants at two separate stages of the programme (antenatal and postnatal). Setting: Community based. Participants: 11 women receiving peer-mentoring support (from first hospital antenatal visit to one year postnatal); 11 lay-workers; 2 research midwives. Results: Lay-workers had difficulty initiating contact with women and failure to establish contact affected their morale adversely. They felt that women understood their intended role poorly and attempted to develop relationships with them by sharing personal experiences and offering friendship; women who participated in the programme appreciated this. Developing a peer-mentor relationship was difficult if women lacked interest in the programme or in continuing contact. External influences on peer-mentoring uptake and delivery included family and friends who could prevent or encourage women’s participation and cause difficulties for the lay-worker both in delivering support and arranging follow-up. Lay-workers providing support to women from a different ethnic background experienced difficulties relating to both language and culture: these were perceived to affect peer-mentor relationships adversely. Major personal difficulties for lay-workers related to time constraints in reconciling mentoring requirements with demands of family and other work. Informing midwives of these difficulties helped identify solutions through training and ongoing professional support for the lay-workers. Conclusions: Lay-worker peer support is appreciated by first time mothers but difficulties in initiating contact, developing peer-mentor relationships and external influences such as family, ethnicity and time constraints are relevant to poor uptake and high staff turnover. In developing peer support programmes, awareness of potential difficulties and of how professional support can help resolve these should improve uptake and thus optimise the evaluations of their effectiveness.

Training of Reaching in Stroke Survivors With Severe and Chronic Upper Limb Paresis Using a Novel Nonrobotic Device: A Randomized Clinical Trial

Background and Purpose—Severe upper limb paresis is a major contributor to disability after stroke. This study investigated the efficacy of a new nonrobotic training device, the Sensorimotor Active Rehabilitation Training (SMART) Arm, that was used with or without electromyography-triggered electrical stimulation of triceps brachii to augment elbow extension, permitting stroke survivors with severe paresis to practice a constrained reaching task.

Methods—A single-blind, randomized clinical trial was conducted with 42 stroke survivors with severe and chronic paresis. Thirty-three participants completed the study, of whom 10 received training using the SMART Arm with electromyography-triggered electrical stimulation, 13 received training using the SMART Arm alone, and 10 received no intervention (control). Training consisted of 12 1-hour sessions over 4 weeks. The primary outcome measure was “upper arm function,” item 6 of the Motor Assessment Scale. Secondary outcome measures included impairment measures; triceps muscle strength, reaching force, modified Ashworth scale; and activity measures: reaching distance and Motor Assessment Scale. Assessments were administered before (0 weeks) and after training (4 weeks) and at 2 months follow-up (12 weeks).

Results—Both SMART Arm groups demonstrated significant improvements in all impairment and activity measures after training and at follow-up. There was no significant difference between these 2 groups. There was no change in the control group.

Conclusions—Our findings indicate that training of reaching using the SMART Arm can reduce impairment and improve activity in stroke survivors with severe and chronic upper limb paresis, highlighting the benefits of intensive task-oriented practice, even in the context of severe paresis.

Identifying strategies to maximise recruitment and retention of practices and patients in a multicentre randomised controlled trial of an intervention to optimise secondary prevention for coronary heart disease in primary care.

Background Recruitment and retention of patients and healthcare providers in randomised controlled trials (RCTs) is important in order to determine the effectiveness of interventions. However, failure to achieve recruitment targets is common and reasons why a particular recruitment strategy works for one study and not another remain unclear. We sought to describe a strategy used in a multicentre RCT in primary care, to report researchers’ and participants’ experiences of its implementation and to inform future strategies to maximise recruitment and retention. Methods In total 48 general practices and 903 patients were recruited from three different areas of Ireland to a RCT of an intervention designed to optimise secondary prevention of coronary heart disease. The recruitment process involved telephoning practices, posting information, visiting practices, identifying potential participants, posting invitations and obtaining consent. Retention involved patients attending reviews and responding to questionnaires and practices facilitating data collection. Results We achieved high retention rates for practices (100%) and for patients (85%) over an 18-month intervention period. Pilot work, knowledge of the setting, awareness of change in staff and organisation amongst participant sites, rapid responses to queries and acknowledgement of practitioners’ contributions were identified as being important. Minor variations in protocol and research support helped to meet varied, complex and changing individual needs of practitioners and patients and encouraged retention in the trial. A collaborative relationship between researcher and practice staff which required time to develop was perceived as vital for both recruitment and retention. Conclusions Recruiting and retaining the numbers of practices and patients estimated as required to provide findings with adequate power contributes to increased confidence in the validity and generalisability of RCT results. A continuous dynamic process of monitoring progress within trials and tailoring strategies to particular circumstances, whilst not compromising trial protocols, should allow maximal recruitment and retention.

Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial

Aims/hypothesis: Patients with type 1 diabetes mellitus are more susceptible than healthy individuals to exercise-induced oxidative stress and vascular endothelial dysfunction, which has important implications for the progression of disease. Thus, in the present study, we designed a randomised double-blind, placebo-controlled trial to test the original hypothesis that oral prophylaxis with vitamin C attenuates rest and exercise-induced free radical-mediated lipid peroxidation in type 1 diabetes mellitus. Methods: All data were collected from hospitalised diabetic patients. The electron paramagnetic resonance spectroscopic detection of spin-trapped a-phenyl-tert-butylnitrone (PBN) adducts was combined with the use of supporting markers of lipid peroxidation and non-enzymatic antioxidants to assess exercise-induced oxidative stress in male patients with type 1 diabetes (HbA1c 7.9±1%, n=12) and healthy controls (HbA1c 4.6±0.5%, n=14). Following participant randomisation using numbers in a sealed envelope, venous blood samples were obtained at rest, after a maximal exercise challenge and before and 2 h after oral ingestion of 1 g ascorbate or placebo. Participants and lead investigators were blinded to the administration of either placebo or ascorbate treatments. Primary outcome was the difference in changes in free radicals following ascorbate ingestion. Resuts: Six diabetic patients and seven healthy control participants were randomised to each of the placebo and ascorbate groups. Diabetic patients (n=12) exhibited an elevated concentration of PBN adducts (p<0.05 vs healthy, n=14), which were confirmed as secondary, lipid-derived oxygen-centred alkoxyl (RO•) radicals (a nitrogen=1.37 mT and aßhydrogen=0.18 mT). Lipid hydroperoxides were also selectively elevated and associated with a depression of retinol and lycopene (p<0.05 vs healthy). Vitamin C supplementation increased plasma vitamin C concentration to a similar degree in both groups (p<0.05 vs pre-supplementation) and attenuated the exercise-induced oxidative stress response (p<0.05 vs healthy). There were no selective treatment differences between groups in the primary outcome variable. Conclusions/ interpretation: These findings are the first to suggest that oral vitamin C supplementation provides an effective prophylaxis against exercise-induced free radical-mediated lipid peroxidation in human diabetic blood.

Does additional support by nurses enhance the effect of a brief smoking cessation intervention in people with moderate to severe chronic obstructive pulmonary disease? A randomised controlled trial

Background: Smoking cessation is the primary disease modifying intervention for chronic obstructive pulmonary disease (COPD).

Cluster randomised controlled trial of an infection control education and training intervention programme focusing on meticillin-resistant Staphylococcus aureus in nursing homes for older people

The aim of this cluster randomised controlled trial was to test the impact of an infection control education and training programme on meticillin-resistant Staphylococcus aureus (MRSA) prevalence in nursing homes. Nursing homes were randomised to intervention (infection control education and training programme; N¼16) or control (usual practice continued; N¼16). Staff in intervention homes were educated and trained (0, 3 and 6 months) in the principles and implementation of good infection control practice with infection control audits conducted in all sites (0, 3, 6 and 12 months) to assess compliance with good practice. Audit scores were fed back to nursing home managers in intervention homes, together with a written report indicating where practice could be improved. Nasal swabs were taken from all consenting residents and staff at 0, 3, 6 and 12 months. The primary outcome was MRSA prevalence in residents and staff, and the secondary outcome was a change in infection control audit scores. In all, 793 residents and 338 staff were recruited at baseline. MRSA prevalence did not change during the study in residents or staff. The relative risk of a resident being colonised with MRSA in an intervention home compared with a control home at 12 months was 0.99 (95% con?dence interval: 0.69, 1.42) after adjustment for clustering. Mean infection control audit scores were signi?cantly higher in the intervention homes (82%) compared with the control homes (64%) at 12 months (P<0.0001). Consideration should be given to other approaches which may help to reduce MRSA in this setting.