The harmonisation of stroke datasets: A case study of four UK datasets

Longitudinal studies of stroke patients play a critical part in developing stroke prognostic models. Stroke longitudinal studies are often limited by small sample sizes, poor recruitment, and high attrition levels. Some of these limitations can be addressed by harmonising and pooling data from existing studies. Thus this thesis evaluated the feasibility of harmonising and pooling secondary stroke datasets to investigate the factors associated with disability after stroke. Data from the Clinical Information Management System for Stroke study (n=312), Stroke Outcome Study 1(n=448), Stroke Outcome Study 2 (n=585), and the Leeds Sentinel Stroke National Audit (n=350) were used in this research. The research conducted in this thesis consisted of four stages. The first stage used the Data Schema and Harmonisation Platform for Epidemiological Research (DataSHaPER) approach to evaluate the feasibility of harmonising and pooling the four datasets that were used in this case study. The second stage evaluated the utility of using multi-group-confirmatory-factor analysis for testing measurement invariance of the GHQ-28 measure prior to pooling the datasets. The third stage evaluated the utility of using Item Response Theory (IRT) models and regression- based methods for linking disability outcome measures. The last stage synthesised the harmonised datasets using multi-group latent class analysis and multi-level Poisson models to investigate the factors associated with disability post-stroke. The main barrier encountered in pooling the four datasets was the heterogeneity in outcome measures. Pooling datasets was beneficial but there was a trade-off between increasing the sample size and losing important covariates. The findings from this present study suggested that the GHQ-28 measure was invariant across the SOS1 and SOS2 stroke cohorts, thus an integrative data analysis of the two SOS datasets was conducted. Harmonising measurement scales using IRT models and regression-based methods was effective for predicting group averages and not individual patient predictions. The analyses of harmonised datasets suggested an association of female gender with anxiety and depressive symptoms post-stroke. This research concludes that harmonising and pooling data from multiple stroke studies was beneficial but there were challenges in measurement comparability. Continued efforts should be made to develop a Data Schema for stroke to facilitate data sharing in stroke rehabilitation research

Association of cardiac rehabilitation and health-related quality of life following acute myocardial infarction

OBJECTIVE: To study the association of cardiac rehabilitation and physical activity with temporal changes in health-related quality of life (HRQoL) following acute myocardial infarction (AMI). METHODS: Evaluation of the Methods and Management of Acute Coronary Events-3 is a nationwide longitudinal prospective cohort study of 4570 patients admitted with an AMI between 1 November 2011 and 17 September 2013. HRQoL was estimated using EuroQol 5-Dimension-3 Level Questionnaire at hospitalisation, 30 days, and 6 and 12 months following hospital discharge. The association of cardiac rehabilitation and self-reported physical activity on temporal changes in HRQoL was quantified using inverse probability of treatment weighting propensity score and multilevel regression analyses. RESULTS: Cardiac rehabilitation attendees had higher HRQoL scores than non-attendees at 30 days (mean EuroQol 5-Visual Analogue Scale (EQ-VAS) scores: 71.0 (SD 16.8) vs 68.6 (SD 19.8)), 6 months (76.0 (SD 16.4) vs 70.2 (SD 19.0)) and 12 months (76.9 (SD 16.8) vs 70.4 (SD 20.4)). Attendees who were physically active ≥150 min/week had higher HRQoL scores compared with those who only attended cardiac rehabilitation at 30 days (mean EQ-VAS scores: 79.3 (SD 14.6) vs 70.2 (SD 17.0)), 6 months (82.2 (SD 13.9) vs 74.9 (SD 16.7)) and 12 months (84.1 (SD 12.1) vs 75.6 (SD 17.0)). Cardiac rehabilitation and self-reported physical activity of ≥150 min/week were each positively associated with temporal improvements in HRQoL (coefficient: 2.12 (95% CI 0.68 to 3.55) and 4.75 (95% CI 3.16 to 6.34), respectively). CONCLUSIONS: Cardiac rehabilitation was independently associated with temporal improvements in HRQoL at up to 12 months following hospitalisation, with such changes further improved in patients who were physically active

Outcomes of conduction system pacing compared to right ventricular pacing as a primary strategy for treating bradyarrhythmia: systematic review and meta-analysis

Background Right ventricular pacing (RVP) may cause electrical and mechanical desynchrony leading to impaired left ventricular ejection fraction (LVEF). We investigated the outcomes of RVP with His bundle pacing (HBP) and left bundle branch pacing (LBBP) for patients requiring a de novo permanent pacemaker (PPM) for bradyarrhythmia. Methods and results Systematic review of randomized clinical trials and observational studies comparing HBP or LBP with RVP for de novo PPM implantation between 01 January 2013 and 17 November 2020 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included all-cause mortality, heart failure hospitalization (HFH), LVEF, QRS duration, lead revision, atrial fibrillation, procedure parameters, and pacing metrics. Overall, 9 studies were included (6 observational, 3 randomised). HBP compared with RVP was associated with decreased HFH (risk ratio [RR] 0.68, 95% confidence interval [CI] 0.49–0.94), preservation of LVEF (mean difference [MD] 0.81, 95% CI − 1.23 to 2.85 vs. − 5.72, 95% CI − 7.64 to -3.79), increased procedure duration (MD 15.17 min, 95% CI 11.30–19.04), and increased lead revisions (RR 5.83, 95% CI 2.17–15.70, p = 0.0005). LBBP compared with RVP was associated with shorter paced QRS durations (MD 5.6 ms, 95% CI − 6.4 to 17.6) vs. (51.0 ms, 95% CI 39.2–62.9) and increased procedure duration (MD 37.78 min, 95% CI 20.04–55.51). Conclusion Of the limited studies published, this meta-analysis found that HBP and LBBP were superior to RVP in maintaining physiological ventricular activation as an initial pacing strategy

Neonatal respiratory distress syndrome: Chest X-ray or lung ultrasound? A systematic review

Background and aim: Neonatal respiratory distress syndrome (NRDS) is a leading cause of morbidity in preterm new-born babies (< 37 weeks gestation age [GA]). The current diagnostic reference standard includes clinical testing and chest radiography (CXR) with associated exposure to ionising radiation. The aim of this review was to compare the diagnostic accuracy of lung ultrasound (LUS) against the reference standard in symptomatic neonates of ≤ 42 weeks GA. Methods: A systematic search of literature published between 1990 and 2016 identified 803 potentially relevant studies. Six studies met the review inclusion criteria and were retrieved for analysis. Quality assessment was performed before data extraction and meta-analysis. Results: Four prospective cohort studies and two case control studies included 480 neonates. All studies were of moderate methodological quality although heterogeneity was evident across the studies. The pooled sensitivity and specificity of LUS were 97% (95% confidence interval [CI] 94%-99%) and 91% (CI: 86%-95%) respectively. False positive diagnoses were made in sixteen cases due to pneumonia (n=8), transient tachypnoea (n=3), pneumothorax (n=1) and meconium aspiration syndrome (n=1); the diagnoses of the remaining three false positive results were not specified. False negatives diagnoses occurred in nine cases, only two were specified as air-leak syndromes. Conclusions: LUS was highly sensitive for the detection of NRDS although there is potential to miss co-morbid air-leak syndromes (ALS). Further research into LUS diagnostic accuracy for neonatal ALS and economic modelling for service integration is required before LUS can replace CXR as the imaging component of the reference standard

Switching methods of self-harm at repeat episodes: Findings from a multicentre cohort study.

BACKGROUND: Self-poisoning and self-injury have widely differing incidences in hospitals and in the community, which has led to confusion about the concept of self-harm. Categorising self-harm simply by a method may be clinically misleading because many hospital-attending patients switch from one method of harm to another on subsequent episodes. The study set out to determine the frequency, pattern, determinants and characteristics of method-switching in self-harm episodes presenting to the general hospital. METHODS: The pattern of repeated self-harm was established from over 33,000 consecutive self-harm episodes in a multicentre English cohort, categorising self-harm methods as poisoning, cutting, other injury, and combined methods. RESULTS: Over an average of 30 months of follow-up, 23% of people repeated self-harm and one-third of them switched method, often rapidly, and especially where the person was male, younger, or had self-harmed previously. Self-poisoning was far less likely than other methods to lead on to switching. LIMITATIONS: Self-harm episodes that do not lead to hospital attendance are not included in these findings but people who self-harmed and went to hospital but were not admitted from the emergency department to the general hospital, or did not receive designated psychosocial assessment are included. People in the study were a mix of prevalent as well as incident cases. CONCLUSIONS: Method of self-harm is fluctuating and unpredictable. Clinicians should avoid false assumptions about people׳s risks or needs based simply on the method of harm

The effect of mechanical loading on osteogenesis of human dental pulp stromal cells in a novel in vitro model

Tooth loss often results in alveolar bone resorption because of lack of mechanical stimulation. Thus, the mechanism of mechanical loading on stem cell osteogenesis is crucial for alveolar bone regeneration. We have investigated the effect of mechanical loading on osteogenesis in human dental pulp stromal cells (hDPSCs) in a novel in vitro model. Briefly, 1 × 107 hDPSCs were seeded into 1 ml 3 % agarose gel in a 48-well-plate. A loading tube was then placed in the middle of the gel to mimic tooth-chewing movement (1 Hz, 3 × 30 min per day, n = 3). A non-loading group was used as a control. At various time points, the distribution of live/dead cells within the gel was confirmed by fluorescence markers and confocal microscopy. The correlation and interaction between the factors (e.g. force, time, depth and distance) were statistically analysed. The samples were processed for histology and immunohistochemistry. After 1-3 weeks of culture in the in-house-designed in vitro bioreactor, fluorescence imaging confirmed that additional mechanical loading increased the viable cell numbers over time as compared with the control. Cells of various phenotypes formed different patterns away from the reaction tube. The cells in the middle part of the gel showed enhanced alkaline phosphatase staining at week 1 but reduced staining at weeks 2 and 3. Additional loading enhanced Sirius Red and type I collagen staining compared with the control. We have thus successfully developed a novel in-house-designed in vitro bioreactor mimicking the biting force to enhance hDPSC osteogenesis in an agarose scaffold and to promote bone formation and/or prevent bone resorption

Kern D-Grid online: UNICORE

OBJECTIVE: To evaluate the effectiveness of pharmacist-led medication review in chronic pain management. MATERIALS AND METHODS: Six electronic databases (Medline, Embase, PsycInfo, CINHAL, CENTRAL, International Pharmaceutical Abstracts) reference lists of retrieved articles and relevant websites were searched for randomized controlled trials published in the English language involving adults with chronic pain. Studies were included if one of the intervention arms had received pharmacist-led medication review independently or as part of a multidisciplinary intervention. Risk of bias was assessed for all the included studies. RESULTS: The search strategy yielded 583 unique articles including 5 randomized controlled trials. Compared with control, meta-analysis showed that participants in the intervention group had: a 0.8-point reduction in pain intensity on a 0 to 10 numerical rating scale at 3 months [95% confidence interval (CI), -1.28 to -0.36] and a 0.7-point reduction (95% CI, -1.19 to -0.20) at 6 months; a 4.84 point (95% CI, -7.38 to -2.29) and -3.82 point (95% CI, -6.49 to -1.14) improvement in physical functioning on a 0- to 68-point function subscale of Western Ontario and McMaster Universities Osteoarthritis Index at 3 and 6 months, respectively; and a significant improvement in patient satisfaction equivalent to a "small to moderate effect." DISCUSSION: Pharmacist-led medication review reduces pain intensity and improves physical functioning and patient satisfaction. However, the clinical significance of these findings remain uncertain due to small effect size and nature of reported data within clinical trials that limits recommendation of wider clinical role of pharmacist in chronic pain management