Peter Kimani - Academia.edu (original) (raw)
Papers by Peter Kimani
Resuscitation, Mar 1, 2018
Aims: To determine patient and health service factors associated with variation in hospital morta... more Aims: To determine patient and health service factors associated with variation in hospital mortality among resuscitated cases of out-of-hospital cardiac arrest (OHCA) with acute coronary syndrome (ACS). Methods: In this cohort study, we used the Myocardial Ischaemia National Audit Project database to study outcomes in patients hospitalised with resuscitated OHCA due to ACS between 2003 and 2015 in the United Kingdom. We analysed variation in inter-hospital mortality and used hierarchical multivariable regression models to examine the association between patient and health service factors with hospital mortality. Results: We included 17604 patients across 239 hospitals. Overall hospital mortality was 28.7%. In 94 hospitals that contributed at least 60 cases, mortality by hospital ranged from 10.7% to 66.3% (median 28.6%, IQR 23.2% to 39.1%)). Patient and health service factors explained 36.1% of this variation. After adjustment for covariates, factors associated with higher hospital mortality included increasing serum glucose, ST-Elevation myocardial infarction (STEMI) diagnosis, and initial admission to a primary percutaneous coronary intervention (pPCI) capable hospital. Hospital OHCA volume was not associated with mortality. The key modifiable factor associated with lower mortality was early reperfusion therapy in STEMI patients. Conclusion: There was wide variation in inter-hospital mortality following resuscitated OHCA due to ACS that was only partially explained by patient and health service factors. Hospital OHCA volume and pPCI capability were not associated with lower mortality. Early reperfusion therapy was associated with lower mortality in STEMI patients.
Purpose Does a non-invasive pulse oximeter probe accurately indicate limb ischaemia with inflatio... more Purpose Does a non-invasive pulse oximeter probe accurately indicate limb ischaemia with inflation of a tourniquet? How are the pulse waveform, perfusion index and oxygen saturations affected? Does pulse oximetry return to normal with restoration of blood flow? Are the findings similar, regardless of which probe is used? Methods Single centre, pilot, proof of concept study. Each volunteer staff member had two probes applied to both lower limbs and then to both upper limbs. One limb had a tourniquet applied (experimental limb). The pulse oximeter trace, perfusion index and oxygen saturations were recorded before tourniquet inflation (timepoint 0), at inflation (timepoint 1), just prior to deflation (timepoint 2) and after deflation when the waveform returned to a biphasic appearance (timepoint 3). Results Changes in both pulse oximeter waveforms occurred within 45 seconds of tourniquet inflation, with flattening of the biphasic trace followed by complete loss of amplitude which norma...
BMJ Open, Feb 1, 2023
Introduction Obstructive sleep apnoea (OSA) is associated with increased cardiovascular mortality... more Introduction Obstructive sleep apnoea (OSA) is associated with increased cardiovascular mortality despite continuous positive airways pressure (CPAP) therapy. This excess risk may be related to increased arrhythmia risk, especially atrial fibrillation (AF). The true incidence of arrhythmia in patients with OSA is unknown. Implantable loop recorders (ILR) are powerful tools for detecting arrhythmias long-term. Cardiac autonomic function may be important in arrhythmogenesis in these patients but needs further study. We aim to identify the true incidence of arrhythmias (especially AF) using ILRs, assess cardiac autonomic function using Holter monitors in patients with OSA and explore cardiovascular outcomes. Methods and analysis A two-centre (University Hospital Coventry and St. Cross Hospital, Rugby) nested cohort study using Reveal LINQ (Medtronic, UK) ILR to identify precise arrhythmia (atrial/ventricular) incidence in patients with moderate-severe OSA. 200 patients will be randomised 1:1 to standard care alone or standard care+ILR (+Holter monitor at baseline and 12 months). The primary objective is to compare arrhythmia detection over 3 years between the two groups. Cardiac autonomic function will be assessed in the ILR-arm at baseline and 12 months post CPAP. Secondary objectives will explore the mechanisms linking OSA and arrhythmia using cardiac autonomic function parameters based on Holter recordings and circulating biomarkers (high sensitivity Troponin-T, N-terminal pro B-type natriuretic peptide, matrix metalloproteinase-9, fibroblast growth factor 23, high sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor-α) before and after CPAP initiation in the ILR-arm. Ethics and dissemination This study has been approved by the Health Research Authority after examination by the Solihull Research and Ethics Committee. The main ethical considerations was the minimally invasive nature of ILR insertion outside of usual care. Patient advisory groups were consulted with a positive outcome for this type of research. We plan on publishing papers in peerreviewed journals based on the primary objective and any interesting findings from secondary objectives. We will endeavour to publish all relevant data. Trial registration number NCT03866148.
Purpose Does a non-invasive pulse oximeter probe accurately indicate limb ischaemia with inflatio... more Purpose Does a non-invasive pulse oximeter probe accurately indicate limb ischaemia with inflation of a tourniquet? How are the pulse waveform, perfusion index and oxygen saturations affected? Does pulse oximetry return to normal with restoration of blood flow? Are the findings similar, regardless of which probe is used? Methods Single centre, pilot, proof of concept study. Each volunteer staff member had two probes applied to both lower limbs and then to both upper limbs. One limb had a tourniquet applied (experimental limb). The pulse oximeter trace, perfusion index and oxygen saturations were recorded before tourniquet inflation (timepoint 0), at inflation (timepoint 1), just prior to deflation (timepoint 2) and after deflation when the waveform returned to a biphasic appearance (timepoint 3). Results Changes in both pulse oximeter waveforms occurred within 45 seconds of tourniquet inflation, with flattening of the biphasic trace followed by complete loss of amplitude which norma...
Open Heart
IntroductionSurvival gaps in acute heart failure (AHF) continue to expand globally. Multinational... more IntroductionSurvival gaps in acute heart failure (AHF) continue to expand globally. Multinational heart failure (HF) registries have highlighted variations between countries. Whether discrepancies in HF practice and outcomes occur across different health systems (ie, private, public or universal healthcare) within a city or between countries remain unclear. Insight into organisational care is also scarce. With increasing public scrutiny of health inequalities, a study to address these limitations is timely.MethodKOLCOV-HF study prospectively compared patients with AHF in public (Nil Ratan Sircar Hospital (NRS)) versus private (Apollo Gleneagles Hospital (AGH)) hospitals of Kolkata, India, and one with universal health coverage in a socioeconomically comparable city of Coventry, England (University Hospitals Coventry & Warwickshire (UHCW)). Data variables were adapted from UK’s National HF Audit programme, collected over 24 months. Predictors of in-hospital mortality and length of ho...
BMC Research Notes
Objective Adolescents and youth constitute a significant proportion of the population in developi... more Objective Adolescents and youth constitute a significant proportion of the population in developing nations. Conventional survey methods risk missing adolescents/youth because their family planning/contraception (FP/C) behavior is hidden. Respondent-driven sampling (RDS), a modified chain-referral recruitment sampling approach, was used to reach unmarried adolescents/youth aged 15–24 in Nairobi, Kenya to measure key FP/C indicators. Seeds were selected and issued with three coupons which they used to invite their peers, male or female, to participate in the study. Referred participants were also given coupons to invite others till sample size was achieved. We report on key implementation parameters following standard RDS reporting recommendations. Results A total of 1674 coupons were issued to generate a sample size of 1354. Coupon return rate was 82.7%. Study participants self-administered most survey questions and missing data was low. Differential enrolment by gender was seen wit...
Health Economics, 2021
Advancing medical knowledge and technologies are increasing understanding of patient heterogeneit... more Advancing medical knowledge and technologies are increasing understanding of patient heterogeneity. Patients previously thought to have the same disease and treated homogeneously can be discovered instead to have subtle differences and respond differently to different treatments (Bieber, 2013; Padmanabhan, 2014). An effective treatment for one patient
BJOG: An International Journal of Obstetrics & Gynaecology, 2019
The following abstracts are some of the top scoring papers presented at the annual meeting of the... more The following abstracts are some of the top scoring papers presented at the annual meeting of the Blair Bell Research Society, now incorporated into the Annual Academic Meeting held at the Royal College of Obstetricians and Gynaecologists on 17-18 January 2019. Dr Neil Ryan (University of Manchester, Manchester) won the prize for the Best Oral Presentation and received £1000 in funding towards presenting his work at an international meeting in 2019. More details of the Society and its meetings can be found at https://www.rcog.org.uk/en/careers-training/academic-og/blair-bell-research-society& Abstracts by submission number 0008 Does perioperative intravenous cefuroxime provide sufficient microbial inhibition in pregnant women undergoing caesarean section? A systematic review of pharmacokinetic studies and surgical site infection rates
Journal of Clinical Pathology, 2020
BackgroundDigital pathology (DP) has the potential to fundamentally change the way that histopath... more BackgroundDigital pathology (DP) has the potential to fundamentally change the way that histopathology is practised, by streamlining the workflow, increasing efficiency, improving diagnostic accuracy and facilitating the platform for implementation of artificial intelligence–based computer-assisted diagnostics. Although the barriers to wider adoption of DP have been multifactorial, limited evidence of reliability has been a significant contributor. A meta-analysis to demonstrate the combined accuracy and reliability of DP is still lacking in the literature.ObjectivesWe aimed to review the published literature on the diagnostic use of DP and to synthesise a statistically pooled evidence on safety and reliability of DP for routine diagnosis (primary and secondary) in the context of validation process.MethodsA comprehensive literature search was conducted through PubMed, Medline, EMBASE, Cochrane Library and Google Scholar for studies published between 2013 and August 2019. The search ...
Statistics in Biopharmaceutical Research, 2020
The COVID-19 pandemic has led to an unprecedented response in terms of clinical research activity... more The COVID-19 pandemic has led to an unprecedented response in terms of clinical research activity. An important part of this research has been focused on randomized controlled clinical trials to evaluate potential therapies for COVID-19. The results from this research need to be obtained as rapidly as possible. This presents a number of challenges associated with considerable uncertainty over the natural history of the disease and the number and characteristics of patients affected, and the emergence of new potential therapies. These challenges make adaptive designs for clinical trials a particularly attractive option. Such designs allow a trial to be modified on the basis of interim analysis data or stopped as soon as sufficiently strong evidence has been observed to answer the research question, without compromising the trial's scientific validity or integrity. In this article, we describe some of the adaptive design approaches that are available and discuss particular issues and challenges associated with their use in the pandemic setting. Our discussion is illustrated by details of four ongoing COVID-19 trials that have used adaptive designs.
PharmacoEconomics, 2021
Introduction Time-to-event data from clinical trials are routinely extrapolated using parametric ... more Introduction Time-to-event data from clinical trials are routinely extrapolated using parametric models to estimate the cost effectiveness of novel therapies, but how this approach performs in the presence of heterogeneous populations remains unknown. Methods We performed a simulation study of seven scenarios with varying exponential distributions modelling treatment and prognostic effects across subgroup and complement populations, with follow-up typical of clinical trials used to appraise the cost effectiveness of therapies by agencies such as the UK National Institute for Health and Care Excellence (NICE). We compared established and emerging methods of estimating population life-years (LYs) using parametric models. We also proved analytically that an exponential model fitted to censored heterogeneous survival times sampled from two distinct exponential distributions will produce a biased estimate of the hazard rate and LYs. Results LYs are underestimated by the methods in the presence of heterogeneity, resulting in either under-or overestimation of the incremental benefit. In scenarios where the overestimation of benefit is likely, which is of interest to the healthcare provider, the method of taking the average LYs from all plausible models has the least bias. LY estimates from complete Kaplan-Meier curves have high variation, suggesting mature data may not be a reliable solution. We explore the effect of increasing trial sample size and accounting for detected treatment-subgroup interactions. Conclusions The bias associated with heterogeneous populations suggests that NICE may need to be more cautious when appraising therapies and to consider model averaging or the separate modelling of subgroups when heterogeneity is suspected or detected.
Bone & Joint Open, 2020
Aims There are reports of a marked increase in perioperative mortality in patients admitted to ho... more Aims There are reports of a marked increase in perioperative mortality in patients admitted to hospital with a fractured hip during the COVID-19 pandemic in the UK, USA, Spain, and Italy. Our study aims to describe the risk of mortality among patients with a fractured neck of femur in England during the early stages of the COVID-19 pandemic. Methods We completed a multicentre cohort study across ten hospitals in England. Data were collected from 1 March 2020 to 6 April 2020, during which period the World Health Organization (WHO) declared COVID-19 to be a pandemic. Patients ≥ 60 years of age admitted with hip fracture and a minimum follow-up of 30 days were included for analysis. Primary outcome of interest was mortality at 30 days post-surgery or postadmission in nonoperative patients. Secondary outcomes included length of hospital stay and discharge destination. Results In total, 404 patients were included for final analysis with a COVID-19 diagnosis being made in 114 (28.2%) pati...
EBioMedicine, 2020
Background: Recurrent pregnancy loss (RPL) is associated with the loss of endometrial mesenchymal... more Background: Recurrent pregnancy loss (RPL) is associated with the loss of endometrial mesenchymal stem-like progenitor cells (eMSC). DPP4 inhibitors may increase homing and engraftment of bone marrow-derived cells to sites of tissue injury. Here, we evaluated the effect of the DPP4 inhibitor sitagliptin on eMSC in women with RPL, determined the impact on endometrial decidualization, and assessed the feasibility of a full-scale clinical trial. Methods: A double-blind, randomised, placebo-controlled feasibility trial on women aged 18 to 42 years with a history of 3 or more miscarriages, regular menstrual cycles, and no contraindications to sitagliptin. Thirtyeight subjects were randomised to either 100 mg sitagliptin daily for 3 consecutive cycles or identical placebo capsules. Computer generated, permuted block randomisation was used to allocate treatment packs. Colony forming unit (CFU) assays were used to quantify eMSC in midluteal endometrial biopsies. The primary outcome measure was CFU counts. Secondary outcome measures were endometrial thickness, study acceptability, and first pregnancy outcome within 12 months following the study. Tissue samples were subjected to explorative investigations. Findings: CFU counts following sitagliptin were higher compared to placebo only when adjusted for baseline CFU counts and age (RR: 1.52, 95% CI: 1.32À1.75, P<0.01). The change in CFU count was 1.68 in the sitagliptin group and 1.08 in the placebo group. Trial recruitment, acceptability, and drug compliance were high. There were no serious adverse events. Explorative investigations showed that sitagliptin inhibits the expression of DIO2, a marker gene of senescent decidual cells. Interpretation: Sitagliptin increases eMSCs and decreases decidual senescence. A large-scale clinical trial evaluating the impact of preconception sitagliptin treatment on pregnancy outcome in RPL is feasible and warranted. Funding: Tommy's Baby Charity.
Trials, 2019
Background Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those as... more Background Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those ascending to high altitudes. Symptoms can include headaches, nausea, insomnia and fatigue. Exposure to high altitude can also lead to high-altitude cerebral oedema (HACE), which is a potential cause of death whilst mountaineering. Generally, AMS precedes the development of HACE. Historical studies have demonstrated the effectiveness of regular dexamethasone administration in reducing the symptoms of AMS. However, the mechanism by which dexamethasone works to reduce symptoms AMS remains poorly understood. Further studies, simulating altitude using hypoxic tents, have characterised the effect of prolonged exposure to normobaric hypoxia on cerebral oedema and blood flow using MRI. This randomised trial assesses the effect of dexamethasone on hypoxia-induced cerebral oedema in healthy adult volunteers. Methods/design D4H is a double-blind placebo-controlled randomised trial assessing the effec...
Current Orthopaedic Practice, 2018
Background: Distal humeral fractures represent about 1% to 2% of adult fractures. Open reduction ... more Background: Distal humeral fractures represent about 1% to 2% of adult fractures. Open reduction and internal fixation (ORIF) has traditionally been the standard treatment; however, fracture comminution and osteoporotic bone may prevent adequate fixation, and total elbow arthroplasty (TEA) is an alternative. The aim of this meta-analysis was to determine which procedure provided superior clinical outcomes for elderly patients with distal humeral fractures. Methods: A systematic review of the literature was conducted in accordance with the PRISMA guidelines. Cases series and comparative studies reporting functional outcomes or complications after TEA and ORIF in patients over 60 yr of age with an acute distal humeral fracture were included. The studies were appraised using validated quality assessment scales. Results were pooled from different studies using meta-analysis techniques, and the functional outcomes, complications, and frequency of revision surgery were compared. Results: ...
![Research paper thumbnail of The role of digital communication in patient–clinician communication for NHS providers of specialist clinical services for young people [the Long-term conditions Young people Networked Communication (LYNC) study]: a mixed-methods study](https://attachments.academia-assets.com/118102739/thumbnails/1.jpg)
](Health Services and Delivery Research, 2018
BackgroundYoung people (aged 16–24 years) with long-term health conditions tend to disengage from... more BackgroundYoung people (aged 16–24 years) with long-term health conditions tend to disengage from health services, resulting in poor health outcomes. They are prolific users of digital communications. Innovative UK NHS clinicians use digital communication with these young people. The NHS plans to use digital communication with patients more widely.ObjectivesTo explore how health-care engagement can be improved using digital clinical communication (DCC); understand effects, impacts, costs and necessary safeguards; and provide critical analysis of its use, monitoring and evaluation.DesignObservational mixed-methods case studies; systematic scoping literature reviews; assessment of patient-reported outcome measures (PROMs); public and patient involvement; and consensus development through focus groups.SettingTwenty NHS specialist clinical teams from across England and Wales, providing care for 13 different long-term physical or mental health conditions.ParticipantsOne hundred and sixty...
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 2019
Frontline gastroenterology, 2018
Colonic mural thickening (MT) is often reported on standard CT examinations of the abdomen and pe... more Colonic mural thickening (MT) is often reported on standard CT examinations of the abdomen and pelvis. It often presents a dilemma for the clinician on whether any further evaluation is needed, especially in the absence of any set guidelines. To evaluate the significance of colonic MT and to assess its correlation with colonoscopy. The search strategy was initially developed in Medline and adapted for use in Embase, Medline, NHS Evidence and TRIP. Studies were included if they had reported colonic MT and subsequent colonoscopy in adults. A total of 9 cohort studies examining 1252 patients were selected having undergone both CT and colonoscopy. Of the 1252 patients with MT, 950 had an abnormal colonoscopy. In the presence of MT, the pooled positive predictive value (PPV) of having any abnormal findings at colonoscopy was 0.73 (95% CI 0.60 to 0.84). The pooled PPV for colorectal cancer, in the presence of MT reporting suspicion of cancer, was 0.63 (95% CI 0.49 to 0.75), and MT suggest...
BMJ open, Mar 23, 2018
Current guidelines recommend abstinence from supervised cardiac rehabilitation (CR) exercise trai... more Current guidelines recommend abstinence from supervised cardiac rehabilitation (CR) exercise training for 6 weeks post-sternotomy. This practice is not based on empirical evidence, thus imposing potentially unnecessary activity restrictions. Delayed participation in CR exercise training promotes muscle atrophy, reduces cardiovascular fitness and prolongs recovery. Limited data suggest no detrimental effect of beginning CR exercise training as early as 2 weeks post-surgery, but randomised controlled trials are yet to confirm this. The purpose of this trial is to compare CR exercise training commenced early (2 weeks post-surgery) with current usual care (6 weeks post-surgery) with a view to informing future CR guidelines for patients recovering from sternotomy. In this assessor-blind randomised controlled trial, 140 cardiac surgery patients, recovering from sternotomy, will be assigned to 8 weeks of twice-weekly supervised CR exercise training commencing at either 2 weeks (early CR) o...
Resuscitation, Mar 5, 2018
To determine patient and health service factors associated with variation in hospital mortality a... more To determine patient and health service factors associated with variation in hospital mortality among resuscitated cases of out-of-hospital cardiac arrest (OHCA) with acute coronary syndrome (ACS). In this cohort study, we used the Myocardial Ischaemia National Audit Project database to study outcomes in patients hospitalised with resuscitated OHCA due to ACS between 2003 and 2015 in the United Kingdom. We analysed variation in inter-hospital mortality and used hierarchical multivariable regression models to examine the association between patient and health service factors with hospital mortality. We included 17604 patients across 239 hospitals. Overall hospital mortality was 28.7%. In 94 hospitals that contributed at least 60 cases, mortality by hospital ranged from 10.7% to 66.3% (median 28.6%, IQR 23.2% to 39.1%)). Patient and health service factors explained 36.1% of this variation. After adjustment for covariates, factors associated with higher hospital mortality included incr...
Resuscitation, Mar 1, 2018
Aims: To determine patient and health service factors associated with variation in hospital morta... more Aims: To determine patient and health service factors associated with variation in hospital mortality among resuscitated cases of out-of-hospital cardiac arrest (OHCA) with acute coronary syndrome (ACS). Methods: In this cohort study, we used the Myocardial Ischaemia National Audit Project database to study outcomes in patients hospitalised with resuscitated OHCA due to ACS between 2003 and 2015 in the United Kingdom. We analysed variation in inter-hospital mortality and used hierarchical multivariable regression models to examine the association between patient and health service factors with hospital mortality. Results: We included 17604 patients across 239 hospitals. Overall hospital mortality was 28.7%. In 94 hospitals that contributed at least 60 cases, mortality by hospital ranged from 10.7% to 66.3% (median 28.6%, IQR 23.2% to 39.1%)). Patient and health service factors explained 36.1% of this variation. After adjustment for covariates, factors associated with higher hospital mortality included increasing serum glucose, ST-Elevation myocardial infarction (STEMI) diagnosis, and initial admission to a primary percutaneous coronary intervention (pPCI) capable hospital. Hospital OHCA volume was not associated with mortality. The key modifiable factor associated with lower mortality was early reperfusion therapy in STEMI patients. Conclusion: There was wide variation in inter-hospital mortality following resuscitated OHCA due to ACS that was only partially explained by patient and health service factors. Hospital OHCA volume and pPCI capability were not associated with lower mortality. Early reperfusion therapy was associated with lower mortality in STEMI patients.
Purpose Does a non-invasive pulse oximeter probe accurately indicate limb ischaemia with inflatio... more Purpose Does a non-invasive pulse oximeter probe accurately indicate limb ischaemia with inflation of a tourniquet? How are the pulse waveform, perfusion index and oxygen saturations affected? Does pulse oximetry return to normal with restoration of blood flow? Are the findings similar, regardless of which probe is used? Methods Single centre, pilot, proof of concept study. Each volunteer staff member had two probes applied to both lower limbs and then to both upper limbs. One limb had a tourniquet applied (experimental limb). The pulse oximeter trace, perfusion index and oxygen saturations were recorded before tourniquet inflation (timepoint 0), at inflation (timepoint 1), just prior to deflation (timepoint 2) and after deflation when the waveform returned to a biphasic appearance (timepoint 3). Results Changes in both pulse oximeter waveforms occurred within 45 seconds of tourniquet inflation, with flattening of the biphasic trace followed by complete loss of amplitude which norma...
BMJ Open, Feb 1, 2023
Introduction Obstructive sleep apnoea (OSA) is associated with increased cardiovascular mortality... more Introduction Obstructive sleep apnoea (OSA) is associated with increased cardiovascular mortality despite continuous positive airways pressure (CPAP) therapy. This excess risk may be related to increased arrhythmia risk, especially atrial fibrillation (AF). The true incidence of arrhythmia in patients with OSA is unknown. Implantable loop recorders (ILR) are powerful tools for detecting arrhythmias long-term. Cardiac autonomic function may be important in arrhythmogenesis in these patients but needs further study. We aim to identify the true incidence of arrhythmias (especially AF) using ILRs, assess cardiac autonomic function using Holter monitors in patients with OSA and explore cardiovascular outcomes. Methods and analysis A two-centre (University Hospital Coventry and St. Cross Hospital, Rugby) nested cohort study using Reveal LINQ (Medtronic, UK) ILR to identify precise arrhythmia (atrial/ventricular) incidence in patients with moderate-severe OSA. 200 patients will be randomised 1:1 to standard care alone or standard care+ILR (+Holter monitor at baseline and 12 months). The primary objective is to compare arrhythmia detection over 3 years between the two groups. Cardiac autonomic function will be assessed in the ILR-arm at baseline and 12 months post CPAP. Secondary objectives will explore the mechanisms linking OSA and arrhythmia using cardiac autonomic function parameters based on Holter recordings and circulating biomarkers (high sensitivity Troponin-T, N-terminal pro B-type natriuretic peptide, matrix metalloproteinase-9, fibroblast growth factor 23, high sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor-α) before and after CPAP initiation in the ILR-arm. Ethics and dissemination This study has been approved by the Health Research Authority after examination by the Solihull Research and Ethics Committee. The main ethical considerations was the minimally invasive nature of ILR insertion outside of usual care. Patient advisory groups were consulted with a positive outcome for this type of research. We plan on publishing papers in peerreviewed journals based on the primary objective and any interesting findings from secondary objectives. We will endeavour to publish all relevant data. Trial registration number NCT03866148.
Purpose Does a non-invasive pulse oximeter probe accurately indicate limb ischaemia with inflatio... more Purpose Does a non-invasive pulse oximeter probe accurately indicate limb ischaemia with inflation of a tourniquet? How are the pulse waveform, perfusion index and oxygen saturations affected? Does pulse oximetry return to normal with restoration of blood flow? Are the findings similar, regardless of which probe is used? Methods Single centre, pilot, proof of concept study. Each volunteer staff member had two probes applied to both lower limbs and then to both upper limbs. One limb had a tourniquet applied (experimental limb). The pulse oximeter trace, perfusion index and oxygen saturations were recorded before tourniquet inflation (timepoint 0), at inflation (timepoint 1), just prior to deflation (timepoint 2) and after deflation when the waveform returned to a biphasic appearance (timepoint 3). Results Changes in both pulse oximeter waveforms occurred within 45 seconds of tourniquet inflation, with flattening of the biphasic trace followed by complete loss of amplitude which norma...
Open Heart
IntroductionSurvival gaps in acute heart failure (AHF) continue to expand globally. Multinational... more IntroductionSurvival gaps in acute heart failure (AHF) continue to expand globally. Multinational heart failure (HF) registries have highlighted variations between countries. Whether discrepancies in HF practice and outcomes occur across different health systems (ie, private, public or universal healthcare) within a city or between countries remain unclear. Insight into organisational care is also scarce. With increasing public scrutiny of health inequalities, a study to address these limitations is timely.MethodKOLCOV-HF study prospectively compared patients with AHF in public (Nil Ratan Sircar Hospital (NRS)) versus private (Apollo Gleneagles Hospital (AGH)) hospitals of Kolkata, India, and one with universal health coverage in a socioeconomically comparable city of Coventry, England (University Hospitals Coventry & Warwickshire (UHCW)). Data variables were adapted from UK’s National HF Audit programme, collected over 24 months. Predictors of in-hospital mortality and length of ho...
BMC Research Notes
Objective Adolescents and youth constitute a significant proportion of the population in developi... more Objective Adolescents and youth constitute a significant proportion of the population in developing nations. Conventional survey methods risk missing adolescents/youth because their family planning/contraception (FP/C) behavior is hidden. Respondent-driven sampling (RDS), a modified chain-referral recruitment sampling approach, was used to reach unmarried adolescents/youth aged 15–24 in Nairobi, Kenya to measure key FP/C indicators. Seeds were selected and issued with three coupons which they used to invite their peers, male or female, to participate in the study. Referred participants were also given coupons to invite others till sample size was achieved. We report on key implementation parameters following standard RDS reporting recommendations. Results A total of 1674 coupons were issued to generate a sample size of 1354. Coupon return rate was 82.7%. Study participants self-administered most survey questions and missing data was low. Differential enrolment by gender was seen wit...
Health Economics, 2021
Advancing medical knowledge and technologies are increasing understanding of patient heterogeneit... more Advancing medical knowledge and technologies are increasing understanding of patient heterogeneity. Patients previously thought to have the same disease and treated homogeneously can be discovered instead to have subtle differences and respond differently to different treatments (Bieber, 2013; Padmanabhan, 2014). An effective treatment for one patient
BJOG: An International Journal of Obstetrics & Gynaecology, 2019
The following abstracts are some of the top scoring papers presented at the annual meeting of the... more The following abstracts are some of the top scoring papers presented at the annual meeting of the Blair Bell Research Society, now incorporated into the Annual Academic Meeting held at the Royal College of Obstetricians and Gynaecologists on 17-18 January 2019. Dr Neil Ryan (University of Manchester, Manchester) won the prize for the Best Oral Presentation and received £1000 in funding towards presenting his work at an international meeting in 2019. More details of the Society and its meetings can be found at https://www.rcog.org.uk/en/careers-training/academic-og/blair-bell-research-society& Abstracts by submission number 0008 Does perioperative intravenous cefuroxime provide sufficient microbial inhibition in pregnant women undergoing caesarean section? A systematic review of pharmacokinetic studies and surgical site infection rates
Journal of Clinical Pathology, 2020
BackgroundDigital pathology (DP) has the potential to fundamentally change the way that histopath... more BackgroundDigital pathology (DP) has the potential to fundamentally change the way that histopathology is practised, by streamlining the workflow, increasing efficiency, improving diagnostic accuracy and facilitating the platform for implementation of artificial intelligence–based computer-assisted diagnostics. Although the barriers to wider adoption of DP have been multifactorial, limited evidence of reliability has been a significant contributor. A meta-analysis to demonstrate the combined accuracy and reliability of DP is still lacking in the literature.ObjectivesWe aimed to review the published literature on the diagnostic use of DP and to synthesise a statistically pooled evidence on safety and reliability of DP for routine diagnosis (primary and secondary) in the context of validation process.MethodsA comprehensive literature search was conducted through PubMed, Medline, EMBASE, Cochrane Library and Google Scholar for studies published between 2013 and August 2019. The search ...
Statistics in Biopharmaceutical Research, 2020
The COVID-19 pandemic has led to an unprecedented response in terms of clinical research activity... more The COVID-19 pandemic has led to an unprecedented response in terms of clinical research activity. An important part of this research has been focused on randomized controlled clinical trials to evaluate potential therapies for COVID-19. The results from this research need to be obtained as rapidly as possible. This presents a number of challenges associated with considerable uncertainty over the natural history of the disease and the number and characteristics of patients affected, and the emergence of new potential therapies. These challenges make adaptive designs for clinical trials a particularly attractive option. Such designs allow a trial to be modified on the basis of interim analysis data or stopped as soon as sufficiently strong evidence has been observed to answer the research question, without compromising the trial's scientific validity or integrity. In this article, we describe some of the adaptive design approaches that are available and discuss particular issues and challenges associated with their use in the pandemic setting. Our discussion is illustrated by details of four ongoing COVID-19 trials that have used adaptive designs.
PharmacoEconomics, 2021
Introduction Time-to-event data from clinical trials are routinely extrapolated using parametric ... more Introduction Time-to-event data from clinical trials are routinely extrapolated using parametric models to estimate the cost effectiveness of novel therapies, but how this approach performs in the presence of heterogeneous populations remains unknown. Methods We performed a simulation study of seven scenarios with varying exponential distributions modelling treatment and prognostic effects across subgroup and complement populations, with follow-up typical of clinical trials used to appraise the cost effectiveness of therapies by agencies such as the UK National Institute for Health and Care Excellence (NICE). We compared established and emerging methods of estimating population life-years (LYs) using parametric models. We also proved analytically that an exponential model fitted to censored heterogeneous survival times sampled from two distinct exponential distributions will produce a biased estimate of the hazard rate and LYs. Results LYs are underestimated by the methods in the presence of heterogeneity, resulting in either under-or overestimation of the incremental benefit. In scenarios where the overestimation of benefit is likely, which is of interest to the healthcare provider, the method of taking the average LYs from all plausible models has the least bias. LY estimates from complete Kaplan-Meier curves have high variation, suggesting mature data may not be a reliable solution. We explore the effect of increasing trial sample size and accounting for detected treatment-subgroup interactions. Conclusions The bias associated with heterogeneous populations suggests that NICE may need to be more cautious when appraising therapies and to consider model averaging or the separate modelling of subgroups when heterogeneity is suspected or detected.
Bone & Joint Open, 2020
Aims There are reports of a marked increase in perioperative mortality in patients admitted to ho... more Aims There are reports of a marked increase in perioperative mortality in patients admitted to hospital with a fractured hip during the COVID-19 pandemic in the UK, USA, Spain, and Italy. Our study aims to describe the risk of mortality among patients with a fractured neck of femur in England during the early stages of the COVID-19 pandemic. Methods We completed a multicentre cohort study across ten hospitals in England. Data were collected from 1 March 2020 to 6 April 2020, during which period the World Health Organization (WHO) declared COVID-19 to be a pandemic. Patients ≥ 60 years of age admitted with hip fracture and a minimum follow-up of 30 days were included for analysis. Primary outcome of interest was mortality at 30 days post-surgery or postadmission in nonoperative patients. Secondary outcomes included length of hospital stay and discharge destination. Results In total, 404 patients were included for final analysis with a COVID-19 diagnosis being made in 114 (28.2%) pati...
EBioMedicine, 2020
Background: Recurrent pregnancy loss (RPL) is associated with the loss of endometrial mesenchymal... more Background: Recurrent pregnancy loss (RPL) is associated with the loss of endometrial mesenchymal stem-like progenitor cells (eMSC). DPP4 inhibitors may increase homing and engraftment of bone marrow-derived cells to sites of tissue injury. Here, we evaluated the effect of the DPP4 inhibitor sitagliptin on eMSC in women with RPL, determined the impact on endometrial decidualization, and assessed the feasibility of a full-scale clinical trial. Methods: A double-blind, randomised, placebo-controlled feasibility trial on women aged 18 to 42 years with a history of 3 or more miscarriages, regular menstrual cycles, and no contraindications to sitagliptin. Thirtyeight subjects were randomised to either 100 mg sitagliptin daily for 3 consecutive cycles or identical placebo capsules. Computer generated, permuted block randomisation was used to allocate treatment packs. Colony forming unit (CFU) assays were used to quantify eMSC in midluteal endometrial biopsies. The primary outcome measure was CFU counts. Secondary outcome measures were endometrial thickness, study acceptability, and first pregnancy outcome within 12 months following the study. Tissue samples were subjected to explorative investigations. Findings: CFU counts following sitagliptin were higher compared to placebo only when adjusted for baseline CFU counts and age (RR: 1.52, 95% CI: 1.32À1.75, P<0.01). The change in CFU count was 1.68 in the sitagliptin group and 1.08 in the placebo group. Trial recruitment, acceptability, and drug compliance were high. There were no serious adverse events. Explorative investigations showed that sitagliptin inhibits the expression of DIO2, a marker gene of senescent decidual cells. Interpretation: Sitagliptin increases eMSCs and decreases decidual senescence. A large-scale clinical trial evaluating the impact of preconception sitagliptin treatment on pregnancy outcome in RPL is feasible and warranted. Funding: Tommy's Baby Charity.
Trials, 2019
Background Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those as... more Background Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those ascending to high altitudes. Symptoms can include headaches, nausea, insomnia and fatigue. Exposure to high altitude can also lead to high-altitude cerebral oedema (HACE), which is a potential cause of death whilst mountaineering. Generally, AMS precedes the development of HACE. Historical studies have demonstrated the effectiveness of regular dexamethasone administration in reducing the symptoms of AMS. However, the mechanism by which dexamethasone works to reduce symptoms AMS remains poorly understood. Further studies, simulating altitude using hypoxic tents, have characterised the effect of prolonged exposure to normobaric hypoxia on cerebral oedema and blood flow using MRI. This randomised trial assesses the effect of dexamethasone on hypoxia-induced cerebral oedema in healthy adult volunteers. Methods/design D4H is a double-blind placebo-controlled randomised trial assessing the effec...
Current Orthopaedic Practice, 2018
Background: Distal humeral fractures represent about 1% to 2% of adult fractures. Open reduction ... more Background: Distal humeral fractures represent about 1% to 2% of adult fractures. Open reduction and internal fixation (ORIF) has traditionally been the standard treatment; however, fracture comminution and osteoporotic bone may prevent adequate fixation, and total elbow arthroplasty (TEA) is an alternative. The aim of this meta-analysis was to determine which procedure provided superior clinical outcomes for elderly patients with distal humeral fractures. Methods: A systematic review of the literature was conducted in accordance with the PRISMA guidelines. Cases series and comparative studies reporting functional outcomes or complications after TEA and ORIF in patients over 60 yr of age with an acute distal humeral fracture were included. The studies were appraised using validated quality assessment scales. Results were pooled from different studies using meta-analysis techniques, and the functional outcomes, complications, and frequency of revision surgery were compared. Results: ...
Health Services and Delivery Research, 2018
BackgroundYoung people (aged 16–24 years) with long-term health conditions tend to disengage from... more BackgroundYoung people (aged 16–24 years) with long-term health conditions tend to disengage from health services, resulting in poor health outcomes. They are prolific users of digital communications. Innovative UK NHS clinicians use digital communication with these young people. The NHS plans to use digital communication with patients more widely.ObjectivesTo explore how health-care engagement can be improved using digital clinical communication (DCC); understand effects, impacts, costs and necessary safeguards; and provide critical analysis of its use, monitoring and evaluation.DesignObservational mixed-methods case studies; systematic scoping literature reviews; assessment of patient-reported outcome measures (PROMs); public and patient involvement; and consensus development through focus groups.SettingTwenty NHS specialist clinical teams from across England and Wales, providing care for 13 different long-term physical or mental health conditions.ParticipantsOne hundred and sixty...
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 2019
Frontline gastroenterology, 2018
Colonic mural thickening (MT) is often reported on standard CT examinations of the abdomen and pe... more Colonic mural thickening (MT) is often reported on standard CT examinations of the abdomen and pelvis. It often presents a dilemma for the clinician on whether any further evaluation is needed, especially in the absence of any set guidelines. To evaluate the significance of colonic MT and to assess its correlation with colonoscopy. The search strategy was initially developed in Medline and adapted for use in Embase, Medline, NHS Evidence and TRIP. Studies were included if they had reported colonic MT and subsequent colonoscopy in adults. A total of 9 cohort studies examining 1252 patients were selected having undergone both CT and colonoscopy. Of the 1252 patients with MT, 950 had an abnormal colonoscopy. In the presence of MT, the pooled positive predictive value (PPV) of having any abnormal findings at colonoscopy was 0.73 (95% CI 0.60 to 0.84). The pooled PPV for colorectal cancer, in the presence of MT reporting suspicion of cancer, was 0.63 (95% CI 0.49 to 0.75), and MT suggest...
BMJ open, Mar 23, 2018
Current guidelines recommend abstinence from supervised cardiac rehabilitation (CR) exercise trai... more Current guidelines recommend abstinence from supervised cardiac rehabilitation (CR) exercise training for 6 weeks post-sternotomy. This practice is not based on empirical evidence, thus imposing potentially unnecessary activity restrictions. Delayed participation in CR exercise training promotes muscle atrophy, reduces cardiovascular fitness and prolongs recovery. Limited data suggest no detrimental effect of beginning CR exercise training as early as 2 weeks post-surgery, but randomised controlled trials are yet to confirm this. The purpose of this trial is to compare CR exercise training commenced early (2 weeks post-surgery) with current usual care (6 weeks post-surgery) with a view to informing future CR guidelines for patients recovering from sternotomy. In this assessor-blind randomised controlled trial, 140 cardiac surgery patients, recovering from sternotomy, will be assigned to 8 weeks of twice-weekly supervised CR exercise training commencing at either 2 weeks (early CR) o...
Resuscitation, Mar 5, 2018
To determine patient and health service factors associated with variation in hospital mortality a... more To determine patient and health service factors associated with variation in hospital mortality among resuscitated cases of out-of-hospital cardiac arrest (OHCA) with acute coronary syndrome (ACS). In this cohort study, we used the Myocardial Ischaemia National Audit Project database to study outcomes in patients hospitalised with resuscitated OHCA due to ACS between 2003 and 2015 in the United Kingdom. We analysed variation in inter-hospital mortality and used hierarchical multivariable regression models to examine the association between patient and health service factors with hospital mortality. We included 17604 patients across 239 hospitals. Overall hospital mortality was 28.7%. In 94 hospitals that contributed at least 60 cases, mortality by hospital ranged from 10.7% to 66.3% (median 28.6%, IQR 23.2% to 39.1%)). Patient and health service factors explained 36.1% of this variation. After adjustment for covariates, factors associated with higher hospital mortality included incr...