Characteristics of alpha-1 antitrypsin deficiency related lung disease exacerbations using a daily symptom diary and urinary biomarkers.

BACKGROUND: Pulmonary exacerbations in alpha-1 antitrypsin deficiency (AATD) related lung disease are a significant contributor to disease burden, as with usual COPD. Separating the early stages of an exacerbation from the day-to-day variation in stable COPD is central to the concerns of both clinicians and patients and has been identified as a research priority by NIHR. Clinical tools that distinguish baseline symptoms from those of an exacerbation could allow early and appropriate treatment of AECOPD to reduce the impact and potentially may slow disease progression thereby improving survival and quality of life. Candidate tools include symptom diaries and biomarkers of infection and acute inflammation. Urinary biomarkers of AECOPD have yet to be explored in AATD related COPD. METHODS: 55 patients with AATD related lung disease with a history of 2 or more AECOPD in the preceding year were prospectively followed for 18 months. Each patient recorded symptom scores daily via an electronic symptom diary (eDiary) based on Bronkotest. Urinary biomarkers for AAT, NE, CRP, TIMP1 and desmosine were measured weekly using a home urinary lateral flow device. During self-reported AECOPD patients were asked to perform urine analysis on the first 7 consecutive days. RESULTS: Type I Anthonisen exacerbations and episodes occurring in autumn/winter lasted longer than Type II/III exacerbations and spring/summer episodes respectively. Median urinary CRP concentration across all study participants increased during Type I AECOPD. eDiary adherence was 68% over a median of 17.8 months (IQR 15.7 to 18.5). CONCLUSIONS: Use of an eDiary and urinary biomarkers to detect and characterise AECOPD remotely in AATD related lung disease is feasible over a prolonged period and paves the way for precision detection of exacerbations.

A Rapid Electronic Cognitive Assessment Measure for Multiple Sclerosis: Validation of Cognitive Reaction, an Electronic Version of the Symbol Digit Modalities Test.

BACKGROUND: Incorporating cognitive testing into routine clinical practice is a challenge in multiple sclerosis (MS), given the wide spectrum of both cognitive and physical impairments people can have and the time that testing requires. Shortened paper and verbal assessments predominate but still are not used routinely. Computer-based tests are becoming more widespread; however, changes in how a paper test is implemented can impact what exactly is being assessed in an individual. The Symbol Digit Modalities Test (SDMT) is one validated test that forms part of the cognitive batteries used in MS and has some computer-based versions. We developed a tablet-based SDMT variant that has the potential to be ultimately deployed to patients' own devices. OBJECTIVE: This paper aims to develop, validate, and deploy a computer-based SDMT variant, the Cognition Reaction (CoRe) test, that can reliably replicate the characteristics of the paper-based SDMT. METHODS: We carried out analysis using Pearson and intraclass correlations, as well as a Bland-Altman comparison, to examine consistency between the SDMT and CoRe tests and for test-retest reliability. The SDMT and CoRe tests were evaluated for sensitivity to disability levels and age. A novel metric in CoRe was found: question answering velocity could be calculated. This was evaluated in relation to disability levels and age for people with MS and compared with a group of healthy control volunteers. RESULTS: SDMT and CoRe test scores were highly correlated and consistent with 1-month retest values. Lower scores were seen in patients with higher age and some effect was seen with increasing disability. There was no learning effect evident. Question answering velocity demonstrated a small increase in speed over the 90-second duration of the test in people with MS and healthy controls. CONCLUSIONS: This study validates a computer-based alternative to the SDMT that can be used in clinics and beyond. It enables accurate recording of elements of cognition relevant in MS but offers additional metrics that may offer further value to clinicians and people with MS.

Level of consciousness on admission to a Heart Attack Centre is a predictor of survival from out-of-hospital cardiac arrest.

INTRODUCTION: The relationship between the neurological status at the time of handover from the ambulance crew to a Heart Attack Centre (HAC) in patients who have achieved return of spontaneous circulation (ROSC) and subsequent outcome, in the context of current treatment standards, is unknown. METHODS: A retrospective review of all patients treated by London Ambulance Service (LAS) from 1(st) April 2011 to 31(st) March 2013 admitted to a HAC in Greater London was undertaken. Neurological status (A - alert; V - responding to voice; P - responding to pain; U - unresponsive) recorded by the ambulance crew on handover was compared with length of hospital stay and survival to hospital discharge. RESULTS: A total of 475 sequential adult cardiac arrests of presumed cardiac origin, achieving ROSC on admission to a HAC were identified. Outcome data was available for 452 patients, of whom 253 (56.0%) survived to discharge. Level of consciousness on admission to the HAC was a predictor of duration of hospital stay (P<0.0001) and survival to hospital discharge (P<0.0001). Of those presenting with a shockable rhythm, 32.3% (120/371) were 'A' or 'V', compared with 9.1% (9/99) of those with non-shockable rhythms (P<0.001). CONCLUSION: Patients with shockable rhythms achieving ROSC are more likely to be conscious (A or V) compared with those with non-shockable rhythms. Most patients who are conscious on admission to the HAC will survive, compared with approximately half of those who are unconscious (P or U), suggesting that critical care is generally appropriate at all levels of consciousness if ROSC has been achieved.

Survival of resuscitated cardiac arrest patients with ST-elevation myocardial infarction (STEMI) conveyed directly to a Heart Attack Centre by ambulance clinicians.

OBJECTIVE: This study reports survival outcomes for patients resuscitated from out-of-hospital cardiac arrest (OHCA) subsequent to ST-elevation myocardial infarction (STEMI), and who were conveyed directly by ambulance clinicians to a specialist Heart Attack Centre for expert cardiology assessment, angiography and possible percutaneous coronary intervention (PCI). METHODS: This is a retrospective descriptive review of data sourced from the London Ambulance Service's OHCA registry over a one-year period. RESULTS: We observed excellent survival rates for our cohort of patients with 66% of patients surviving to be discharged from hospital, the majority of whom were still alive after one year. Those who survived tended to be younger, to have had a witnessed arrest in a public place with an initial cardiac rhythm of VF/VT, and to have been transported to the specialist centre more quickly than those who did not. CONCLUSION: A system allowing ambulance clinicians to autonomously convey OHCA STEMI patients who achieve a return of spontaneous circulation directly to a Heart Attack Centre is highly effective and yields excellent survival outcomes.

Increases in survival from out-of-hospital cardiac arrest: a five year study.

OBJECTIVE: This study reports improvements in survival from out-of-hospital cardiac arrest in London over a five year period from 2007 to 2012 and explores the potential reasons for the very striking increases observed. METHODS: Data from the London Ambulance Service's cardiac arrest registry from 2007 to 2012 were analysed retrospectively for all patients who met the Utstein comparator group criteria (an arrest of a presumed cardiac cause that was bystander witnessed with an initial rhythm of VF/VT). RESULTS: We observed an increase in survival from out-of-hospital cardiac arrest during the five year period, with incremental improvements each year from 12% to 32% for the Utstein comparator group of patients. CONCLUSION: We suggest that a range of important changes made to pre-hospital cardiac care in London over the last five years have contributed to the observed increase in survival over the study period. In addition we advocate a range of further initiatives to continue improving survival from out-of-hospital cardiac arrest.

The acute impact of a hematopoietic allograft on lung function and inflammation: a prospective observational study.

BACKGROUND: No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT) on pulmonary inflammation or lung function. METHODS: Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant. RESULTS: Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94%) were included in the study. Compared to baseline, pulmonary inflammation as measured by exhaled nitric oxide increased after receiving a HSCT with the largest increment seen at three months (+6.0 ppb, 95%CI: +0.4 to +11.5), and this was sustained at six months. Percent predicted forced expiratory volume in one second decreased over the same period, with the largest decrease observed at six weeks (-5.9%, 95% CI: -8.9 to -2.9), and this was also sustained over a six month period. Similar associations were observed for FVC. A larger increase in exhaled nitric oxide from baseline at six weeks and three months may be associated with decreased mortality (p=0.06, p=0.04 respectively). CONCLUSION: Our data demonstrate that recipients of an allogeneic HSCT experience an increase in biomarkers of pulmonary inflammation and a decrease in lung function in the first six months after the procedure. If independently validated in other study populations, these observations could have potential as a prognostic biomarker for this patient group.

Image jitter enhances visual performance when spatial resolution is impaired.

PURPOSE: Visibility of low-spatial frequency stimuli improves when their contrast is modulated at 5 to 10 Hz compared with stationary stimuli. Therefore, temporal modulations of visual objects could enhance the performance of low vision patients who primarily perceive images of low-spatial frequency content. We investigated the effect of retinal-image jitter on word recognition speed and facial emotion recognition in subjects with central visual impairment. METHODS: Word recognition speed and accuracy of facial emotion discrimination were measured in volunteers with AMD under stationary and jittering conditions. Computer-driven and optoelectronic approaches were used to induce retinal-image jitter with duration of 100 or 166 ms and amplitude within the range of 0.5 to 2.6° visual angle. Word recognition speed was also measured for participants with simulated (Bangerter filters) visual impairment. RESULTS: Text jittering markedly enhanced word recognition speed for people with severe visual loss (101 ± 25%), while for those with moderate visual impairment, this effect was weaker (19 ± 9%). The ability of low vision patients to discriminate the facial emotions of jittering images improved by a factor of 2. A prototype of optoelectronic jitter goggles produced similar improvement in facial emotion discrimination. Word recognition speed in participants with simulated visual impairment was enhanced for interjitter intervals over 100 ms and reduced for shorter intervals. CONCLUSIONS: Results suggest that retinal-image jitter with optimal frequency and amplitude is an effective strategy for enhancing visual information processing in the absence of spatial detail. These findings will enable the development of novel tools to improve the quality of life of low vision patients.

Childhood constipation.

Idiopathic constipation in childhood is a problem that can cause a myriad of difficulties to both the child or young person and their family. There are a number of precipitating factors that may result in painful or infrequent bowel movements and/or soiling. Empowering children and young people together with their parents and carers forms one part of the treatment plan, but it is the adequate and effective use of laxative therapy alongside diet and lifestyle modifications and appropriate advice and support that can best help children to overcome this poorly understood condition. Professionals need to demystify how the bowel works and help children and young people to overcome their embarrassment in seeking help for this common childhood condition. The new NICE guideline will help all practitioners in recognising their role in helping children, young people and their families.

A heat-stable hepatitis B vaccine formulation.

The purpose of the present study was to develop a formulation of recombinant hepatitis B vaccine with improved stability at elevated temperatures. A validated in vitro antigen reactivity assay was used to measure the stability of the vaccine. The formulation development focused on modification of the interactions between the antigen and aluminum hydroxide adjuvant and subsequent optimization of the ionic aqueous environment of the adsorbed vaccine. A formulation of hepatitis B vaccine containing 40 mM histidine and 40 mM phosphate at pH 5.2 had considerably improved stability at elevated temperatures as measured by the in vitro antigen reactivity assay. The formulation exhibited 9-week stability at 55 degrees C and was subsequently shown to be stable both at 37 degrees C and at 45 degrees C for at least 6 months based on the in vitro antigen reactivity and immunogenicity in mice. The formulation comprises only excipients which have a history of safe use in approved drug products. The new vaccine formulation has the potential to be used outside the cold chain for part of its shelf life. This may improve the immunization coverage, simplify the logistics for outreach immunization, and ensure the potency of the vaccine in areas where the cold chain is insufficient.