QT peak prolongation predicts cardiac death following stroke

Cardiac death has been linked in many populations to prolongation of the QT interval (QTe). However, basic science research suggested that the best estimate of the time point when repolarisation begins is near the T-wave peak. We found QT peak (QTp) was longer in hypertensive subjects with LVH. A prolonged “depolarisation” phase, rather than “repolarisation” (T peak to T end) might therefore account for the higher incidence of cardiac death linked to long QT. Hypothesis: We have tested the hypothesis that QT peak (QTp) prolongation predicts cardiac death in stroke survivors. Methods and Results: ECGs were recorded from 296 stroke survivors (152 male), mean age 67.2 (SD 11.6) approximately 1 year after the event. Their mean blood pressure was 152/88 mmHg (SD 29/15mmHg). These ECGs were digitised by one observer who was blinded to patient outcome. The patients were followed up for a median of 3.3 years. The primary endpoint was cardiac death. A prolonged heart rate corrected QT peak (QTpc) of lead I carried the highest relative risk of death from all cause as well as cardiac death, when compared with the other more conventional QT indices. In multivariate analyses, when adjusted for conventional risk factors of atherosclerosis, a prolonged QTpc of lead I was still associated with a 3-fold increased risk of cardiac death. (adjusted relative risk 3.0 [95% CI 1.1 - 8.5], p=0.037). Conclusion: QT peak prolongation in lead I predicts cardiac death after strok

Towards understanding the clinical significance of QT peak prolongation: a novel marker of myocardial ischemia independently demonstrated in two prospective studies

Background: QT peak prolongation identified patients at risk of death or non-fatal MI. We tested the hypothesis that QT peak prolongation might be associated with significant myocardial ischaemia in two separate cohorts to see how widely applicable the concept was. Methods and Results: In the first study, 134 stroke survivors were prospectively recruited and had 12-lead ECGs and Nuclear myocardial perfusion scanning. QT peak was measured in lead I of a 12-lead ECG and heart rate corrected by Bazett’s formula (QTpc). QTpc prolongation to 360ms or more was 92% specific at diagnosing severe myocardial ischaemia. This hypothesis-generating study led us to perform a second prospective study in a different cohort of patients who were referred for dobutamine stress echocardiography. 13 of 102 patients had significant myocardial ischaemia. Significant myocardial ischaemia was associated with QT peak prolongation at rest (mean 354ms, 95% CI 341-367ms, compared with mean 332ms, 95% CI 327-337ms in those without significant ischaemia; p=0.002). QT peak prolongation to 360ms or more was 88% specific at diagnosing significant myocardial ischaemia in the stress echocardiography study. QT peak prolongation to 360ms or more was associated with over 4-fold increase odds ratio of significant myocardial ischaemia. The Mantel- Haenszel Common Odds Ratio Estimate=4.4, 95% CI=1.2-16.0, p=0.023. Conclusion: QT peak (QTpc) prolongation to 360ms or more should make us suspect the presence of significant myocardial ischaemia. Such patients merit further investigations for potentially treatable ischaemic heart disease to reduce their risk of subsequent death or non-fatal MI

Supplemental Iodide for Preterm Infants and Developmental Outcomes at 2 Years:an RCT

Background The recommendation for enteral iodide intake for preterm infants is 30–40 μg/kg/day and 1μg/kg/day for parenteral intake. Preterm infants are vulnerable to iodide insufficiency and thyroid dysfunction. The hypothesis tested whether, compared to placebo, iodide supplementation of preterm infants improves neurodevelopment. Methods A randomized controlled trial of iodide supplementation versus placebo in infants <31 weeks’ gestation. Trial solutions (sodium iodide or sodium chloride; dose 30μg/kg/day) were given within 42 hours of birth to the equivalent of 34 weeks’ gestation. The only exclusion criterion was maternal iodide exposure during pregnancy or delivery. Whole blood levels of thyroxine, thyrotropin and thyroid binding globulin were measured on four specific postnatal days. The primary outcome was neurodevelopmental status at two years’ of age, measured using the Bayley-III scales. The primary analyses are by intention-to-treat and data are presented also for survivors. Results 1,273 infants (637 intervention, 636 placebo) were recruited from 21 UK neonatal units. 131 infants died, and neurodevelopmental assessments were undertaken in 498 iodide and 499 placebo supplemented infants. There were no significant differences between the intervention and placebo groups in the primary outcome: mean difference Cognitive score, -0.34, 95% confidence interval (CI) -2.57 to 1.89; Motor composite score, 0.21, 95% CI -2.23 to 2.65; Language composite score, -0.05, 95%CI -2.48 to 2.39. There was evidence of weak interaction between iodide supplementation and hypothyroxinemic status in the Language composite score and one subtest score. Conclusions Overall iodide supplementation provided no benefit to neurodevelopment measured at 2 years of age

Tailored second line therapy in asthmatic children with the arginine-16 genotype

The arginine-16 beta-2 receptor genotype confers increased susceptibility to exacerbations in asthmatic children taking regular long acting beta-2 agonists. We therefore evaluated using montelukast as an alternative to salmeterol as tailored second line asthma controller therapy in children expressing this susceptible genotype. 62 persistent asthmatic children with the homozygous arginine-16 genotype were randomized to receive salmeterol 50ug bid or montelukast 5/10mg od as add on to inhaled fluticasone for 1 year. School absences (the primary outcome) were reduced with montelukast arm compared to salmeterol: difference in score = 0.40 (95%CI 0.07-0.87) p=0.005. Albuterol use was also reduced with montelukast compared with salmeterol: difference in score = 0.47 (95%CI 0.16-0.79) p<0.0001. Greater improvements occurred in both symptom and quality of life scores with montelukast vs salmeterol, while there was no difference in FEV1. Montelukast may be suitable as tailored second line controller therapy instead of salmeterol in asthmatic children expressing the susceptible arginine-16 genotype - moving towards a personalised medicine approach to management

Reflecting on the methodological challenge of recruiting older care home residents to podiatry research

IntroductionSuccessful randomisd controlled trials (RCTs) require successful participant recruitment; poor recruitment leads to poor, under-powered studies, and may waste grant funds. Recruitment of older care home residents to RCTs is challenging. This is problematic for podiatry, because older people within care home settings are high users of podiatry services; therefore it is essential that strategies are employed to maximise recruitment to RCTs.We describe the experience of recruiting to a feasibility study of a podiatry intervention to reduce falls in care home residents in the East of Scotland. This was the first phase of a two phase project consisting of the feasibility study to acquire data (recruitment strategy, selection of suitable outcome measures) to inform the conduct of the second phase, an exploratory RCT. Recruitment difficulties became apparent early in the study. Difficulties arose when it came to assessing whether or not potential participants fulfilled certain inclusion criteria:(1) Presence of foot pain (defined as foot pain lasting for at least a day in the last month and a positive response of “some days” or “most/every days” to at least one item on the Manchester Foot Pain and Disability Index (MFPDI))(2) Ability to provide informed consent. The reasons for these difficulties are that (1) we discovered that in the area in which our study was conducted, the majority of care home residents receive basic NHS podiatry care to treat any superficial lesions (i.e. pathological nails and skin callus) thus the prevalence of foot pain resulting from these lesions was lower than we had originally anticipated, and (2) the care homes that we engaged for this phase of the study had residents who were far more dependent and with much higher levels cognitive impairment than we anticipated, making obtaining informed consent difficult. Based on the existing inclusion criteria, it was deemed unlikely that we would meet our recruitment target for the subsequent exploratory randomised controlled trial (n=40).MethodsFollowing discussion with co-applicants we proposed to make two changes in order to improve recruitment, whilst maintaining the scientific integrity of the protocol:(1) We engaged with care homes that cater for less dependent residents in order to improve the likelihood of obtaining informed consent. (2) Since evidence shows that there are several foot and ankle characteristics (toe muscle weakness, hallux valgus, decreased ankle flexibility and strength) that are associated with falls but which do not necessarily cause pain, we widened the inclusion criteria by removing foot pain as a criterion. The recruitment difficulties required a 3 month prolongation of the study duration.ResultsAs a result of tailoring the recruitment strategy early in the feasibility study, we recruited rapidly to the exploratory RCT. We have exceeded our target (n=48).ConclusionsCare home residents represent a convenient population for data collection, but frailty and multiple co-morbidities may make successful recruitment to intervention studies challenging. Whilst the adaptations used in this study may have implications for external validity, this work underlines the importance of testing recruitment strategies at an early stage.Journal supplement-The College of Podiatry Annual Conference 2014: meeting abstract

Finding your feet: The development of a podiatry intervention to reduce falls in care home residents.

IntroductionPeople who live in care homes often fall. Foot and ankle muscle weakness, sub-optimal footwear, and common foot problems such as corns and hallux valgus are known and potentially modifiable contributory factors to falls in older people. Conducting a randomised controlled trial in a care home setting to address these issues is challenging and presents a number of uncertainties that need to be addressed prior to undertaking a phase III trial. Therefore, this study used a qualitative approach to assess the feasibility and acceptability of a podiatry falls intervention to care home residents and staff. The data acquired during this qualitative preparatory phase will inform the conduct of a subsequent exploratory randomised controlled trial of a podiatry intervention to reduce falls in care homes.Methods ParticipantsPermanent care home residents with a history of falls, mini mental state examination (MMSE) >9, ability to provide informed consent (n=8); staff (n=5).InterventionResidents, supported by care home staff, participated in a 3-month feasibility-testing phase of an intervention (footwear and orthoses provision, toe and ankle muscle strengthening programme).EvaluationExercise frequency was recorded in logbooks by staff. To assess acceptability and perceptions of feasibility at the conclusion of the 3-month testing period, face to face semi-structured interviews were conducted.Data analysisDescriptive data of exercise frequency were calculated. Analysis of the qualitative data employed a constant-comparative process embedded within the wider framework method to identify emerging themes and concepts to inform the intervention remodelling and development.ResultsFidelity30/57(52.6%) logbooks returned; 11(19.3%) completed in full. Adherence ranged between exercises not having been completed at all in some weeks, to three times per week (optimal) in others.FacilitatorsParticipation in the programme was well received and fitted into care home routines. The exercise component of the intervention was easily carried out and took no longer then 10 minutes to complete. Participants reported that explanation of the aims of the programme at each exercise session was beneficial to adherence. Some residents saw peer support as important; however other residents preferred one-to-one sessions. Footwear and orthoses were well received by the participants.BarriersDiscomfort during exercises, cognitive impairment and illness were barriers reported by residents and staff. A major barrier to adherence was limited access for all staff to training resulting in exercises not being performed when trained staff were not available.ConclusionsA podiatry intervention to reduce falls in care homes is feasible and acceptable. Delivery to residents should be tailored to individual preferences (taking into account goals, targets, and information). Accessing training via DVD or an online resource may improve the reach of the training, facilitating adherence and fidelity. These findings have informed intervention development and modes of delivery for an exploratory randomised controlled trial that is currently underway.Journal supplement - The College of Podiatry Annual Conference 2014: meeting abstract

Podiatry intervention versus usual care to prevent falls in care homes: pilot randomised controlled trial (the PIRFECT study)

BackgroundCommon foot problems are independent risk factors for falls in older people. There is evidence that podiatry can prevent falls in community-dwelling populations. The feasibility of implementing a podiatry intervention and trial in the care home population is unknown. To inform a potential future definitive trial, we performed a pilot randomised controlled trial to assess: (i) the feasibility of a trial of a podiatry intervention to reduce care home falls, and (ii) the potential direction and magnitude of the effect of the intervention in terms of number of falls in care home residents.MethodsInformed by Medical Research Council guidance on developing and evaluating complex interventions, we conducted a single blind, pilot randomised controlled trial in six care homes in the East of Scotland. Participants were randomised to either: (i) a three month podiatry intervention comprising core podiatry care, foot and ankle exercises, orthoses and footwear provision or (ii) usual care. Falls-related outcomes (number of falls, time to first fall) and feasibility-related outcomes (recruitment, retention, adherence, data collection rates) were collected. Secondary outcomes included: generic health status, balance, mobility, falls efficacy, and ankle joint strength.Results474 care home residents were screened. 43 (9.1%) participants were recruited: 23 to the intervention, 20 to control. Nine (21%) participants were lost to follow-up due to declining health or death. It was feasible to deliver the trial elements in the care home setting. 35% of participants completed the exercise programme. 48% reported using the orthoses ‘all or most of the time’. Completion rates of the outcome measures were between 93% and 100%. No adverse events were reported. At the nine month follow-up period, the intervention group per-person fall rate was 0.77 falls vs. 0.83 falls in the control group.ConclusionsA podiatry intervention to reduce falls can be delivered to care home residents within a pilot randomised controlled trial of the intervention. Although not powered to determine effectiveness, these preliminary data provide justification for a larger trial, incorporating a full process evaluation, to determine whether this intervention can significantly reduce falls in this high-risk population.Trial registrationClinicalTrials.gov identifier: NCT02178527; Date of registration: 17 June 2014

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD