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Papers by salma ayis

Research paper thumbnail of Azithromycin in patients with Covid-19; a systematic review and metanalysis

Background: Azithromycin (AZM) has been widely used in the management of Covid-19. However, the e... more Background: Azithromycin (AZM) has been widely used in the management of Covid-19. However, the evidence on its actual effects remains disperse and difficult to apply in clinical settings. This systematic review and metanalysis summarizes the studies on the beneficial and adverse effect of AZM in patients with Covid-19. Methods: The PRISMA 2020 statement criteria were followed. Randomized controlled trials (RCTs) and observational studies comparing clinical outcomes of patients treated, and not treated, with AZM, indexed until the 5th of July 2021, were searched in PubMed, Embase, The Web of Science, Scopus, The Cochrane Central Register of Controlled Trials, and MedRXivs. We used Random-effects models to estimate pooled effect size from aggregate data. Results: The initial search produced 4950 results. Finally, 16 studies, five RCTs and 11 with an observational design, with a total of 22984 patients, were included. The metanalysis showed no difference in mortality for those treated...

Research paper thumbnail of Evaluation of NHS Practitioner Health: capturing mental health outcomes using five instruments

BJPsych Open, 2021

Background NHS Practitioner Health is the England wide programme providing mental health and addi... more Background NHS Practitioner Health is the England wide programme providing mental health and addiction healthcare to doctors and dentists. Outcomes are assessed using five measures. Aims To contribute to a service evaluation of NHS Practitioner Health. To determine responsiveness to change and compare outcome measures. Method Measures were completed at baseline and 6 months: Generalized Anxiety Disorder Assessment (GAD-7), Perceived Stress Scale (PSS), Patient Health Questionaire-9 (PHQ-9), Warwick-Edinburgh Mental Wellbeing scale (WEMWBS), Psychological Outcome Profiles (PSYCHLOPS). Responsiveness to change was determined using effect size with improvement threshold ≥0.80. Instruments were compared using Bland–Altman plots. Results Our sample, n = 402; with 14 (3.5%) excluded for missing data; final sample, n = 388. All measures showed strong mean effect sizes: PSYCHLOPS 1.86 (95%CI 1.73–1.99), 75.8% ≥0.80; PSS 1.48 (1.34–1.62), 64.4% ≥0.80; WEMWBS 1.24 (1.13–1.35), 58.2% ≥0.80; GA...

Research paper thumbnail of The association between 7 day consultant wards and mortality risk in stroke patients admitted at the weekend

Research paper thumbnail of Effect of Iron Isomaltoside on Skeletal Muscle Energetics in Patients with Chronic Heart Failure and Iron Deficiency: The FERRIC-HF II Randomized Mechanistic Trial

Circulation

BACKGROUND Iron repletion augments exercise capacity in chronic heart failure (HF), but there is ... more BACKGROUND Iron repletion augments exercise capacity in chronic heart failure (HF), but there is a lack of mechanistic data explaining how iron could augment exercise performance despite minimal changes in hemoglobin (Hb). Besides Hb, iron is an obligate component of mitochondrial enzymes that generate cellular energy in the form of adenosine triphosphate and phosphocreatine (PCr). Dynamic phosphorus magnetic resonance spectroscopy is a noninvasive tool that quantifies in vivo muscle energetics by measuring the kinetics of PCr recovery after exertion. We tested the hypothesis that intravenous iron repletion in chronic HF enhances skeletal muscle energetics as reflected by shorter PCr recovery half-times (PCr t1/2) on phosphorus magnetic resonance spectroscopy. METHODS We enrolled 40 patients (50% anemic) with chronic HF, New York Heart Association class ≥II, left ventricular ejection fraction ≤45%, and iron deficiency (ferritin<100 μg/L or 100-300 μg/L with transferrin saturation <20%). Subjects underwent stratified (anemic versus nonanemic) randomization (1:1) to a single, double-blinded, total dose infusion of iron isomaltoside or saline placebo with end points reassessed early at 2 weeks posttreatment to minimize confounding from exercise adaptation. The primary end point was PCr t1/2 at 2 weeks. Secondary end points included ADP recovery half-time (ADP t1/2; energetic marker), iron status, symptoms, Hb, exercise capacity, and safety. RESULTS In the total population, treatment groups were similar at baseline. At 2 weeks, iron isomaltoside improved PCr t1/2 (adjusted difference, -6.8 s; 95% CI, 11.5 to -2.1; P=0.006), ADP t1/2 (-5.3 s; 95% CI, -9.7 to -0.9; P=0.02), ferritin (304 ng/mL; 95% CI, 217-391; P<0.0001), transferrin saturation (6.8%; 95% CI, 2.7-10.8; P=0.002), New York Heart Association class (-0.23; 95% CI, -0.46 to -0.01; P=0.04), resting respiratory rate (-0.7 breaths/min; 95% CI, -1.2 to -0.2; P=0.009), and postexercise Borg dyspnea score (-2.0; 95% CI, -3.7 to -0.3; P=0.04), but not Hb (2.4 g/L; 95% CI, -3.5 to 8.4; P=0.41). Adverse events were similar between groups. In subgroup analyses, iron isomaltoside improved PCr t1/2 in anemic (-8.4 s; 95% CI, -16.7 to -0.2; P=0.04) and nonanemic (-5.2 s; 95% CI, -10.6 to 0.2; P=0.06) cohorts. CONCLUSIONS In patients with chronic HF and iron deficiency, a total repletion dose of iron isomaltoside given at a single sitting is well tolerated and associated with faster skeletal muscle PCr t1/2 at 2 weeks, implying better mitochondrial function. Augmented skeletal muscle energetics might therefore be an important mechanism via which iron repletion confers benefits in chronic HF despite minimal Hb changes. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005592-13/GB . Unique identifier: EudraCT 2012-005592-13.

Research paper thumbnail of Disparities in the management of cardiovascular risk factors in patients with psychiatric disorders: a systematic review and meta-analysis

Psychological medicine, 2018

The high cardiovascular (CV) morbidity and mortality reported for patients with psychiatric disor... more The high cardiovascular (CV) morbidity and mortality reported for patients with psychiatric disorders may possibly be due to a poorer management of CV risk factors (CVRFs). However, these healthcare disparities remain poorly understood. In this paper, studies comparing the management of smoking, diabetes, hypertension and dyslipidaemia, in patients with and without depression, anxiety, schizophrenia, bipolar or personality disorder, were reviewed. Prospective studies comparing rates of screening, diagnosis, treatment and control of CVRFs were searched in PubMed, Embase, PsychInfo, Scopus and Web of Science (inception to January 2017). The Meta-analysis of Observational Studies in Epidemiology (MOOSE) criteria were used. Studies were assessed for quality. Wherever possible, meta-analyses were conducted to summarize the findings. Twenty studies, out of the 18 333 references initially identified, were included. Most studies were heterogeneous in design. Two areas permitted meta-analyse...

Research paper thumbnail of The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis

Journal of pain research, 2017

Osteoarthritis (OA) is the most prevalent arthritis worldwide and is characterized by chronic pai... more Osteoarthritis (OA) is the most prevalent arthritis worldwide and is characterized by chronic pain and impaired physical function. We hypothesized that heightened pain in hand OA could be reduced with duloxetine or pregabalin. In this prospective, randomized clinical study, we recruited 65 participants, aged 40-75 years, with a Numerical Rating Scale (NRS) for pain of at least 5. Participants were randomized to one of the following three groups: duloxetine, pregabalin, and placebo. The primary endpoint was the NRS pain score, and the secondary endpoints included the Australian and Canadian Hand Osteoarthritis Index (AUSCAN) pain, stiffness, and function scores and quantitative sensory testing by pain pressure algometry. After 13 weeks, compared to placebo, ANOVA found significant differences between the three groups (P=0.0078). In the intention-to-treat analysis, the pregabalin group showed improvement for NRS pain (P=0.023), AUSCAN pain (P=0.008), and AUSCAN function (P=0.009), but...

Research paper thumbnail of Pre-operative frailty scores as markers for assessing disability-free survival in cardiac surgery?

Journal of Cardiothoracic and Vascular Anesthesia

Research paper thumbnail of Hypertension risk and clinical care in patients with bipolar disorder or schizophrenia; a systematic review and meta-analysis

Journal of Affective Disorders

Background: A higher cardiovascular morbidity and mortality has been observed in patients with bi... more Background: A higher cardiovascular morbidity and mortality has been observed in patients with bipolar disorder (BPD) or schizophrenia, partly due to an increased risk of hypertension (HTN), or a less effective care of it. This systematic review and meta-analysis, presents a critical appraisal and summary of the studies addressing the risk of HTN, or the differences in its care, for those with schizophrenia or BPD. Methods: Prospective studies were searched in PubMed, Embase, PsycINFO, Scopus, and the Web of Science, from database inception to June 2017. A meta-analysis was undertaken to obtain pooled estimates of the risk of HTN. Results: Five studies reporting the risk of HTN, and five studies presenting differences in its clinical care, were identified. An increased risk of HTN was observed for BPD patients, with an overall Incidence Rate Ratio 1.27(1.15-1.40). The pooled Incidence Rate Ratio of HTN for those with schizophrenia was 0.94 (0.75-1.14). A poorer care of HTN (lower rates of screening, prescription, and adherence) was reported in four studies of schizophrenia, and two of BPD patients, compared to people without these conditions. Limitations: reduced number of studies on risk and care of HTN on patients with BPD or schizophrenia. Conclusions: Limited evidence suggests that patients with BPD have a higher risk of HTN. Patients with schizophrenia and BPD receive poor care of HTN. Understanding the risk of HTN, and the differences in its care, is essential for clinicians to reduce the cardiovascular morbidity and overall mortality of these patients.

Research paper thumbnail of Effects of aliskiren on mortality, cardiovascular outcomes and adverse events in patients with diabetes and cardiovascular disease or risk: A systematic review and meta-analysis of 13,395 patients

Diabetes and Vascular Disease Research

If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.

Research paper thumbnail of P 34 Does performance of mean arterial blood pressure for the screening of preeclampsia improve after controlling for the use of anti-hypertensive medication?

Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health

Question Mean arterial pressure (MAP) is a useful biomarker for the screening of preeclampsia (PE... more Question Mean arterial pressure (MAP) is a useful biomarker for the screening of preeclampsia (PE). However, MAP, a function of cardiac output and peripheral resistance, is dependent on other maternal characteristics and, for its effective use in screening, these need to be taken into account. One such characteristic is the use of anti-hypertensive medication. The aim of our study was to evaluate the impact of the use of anti-hypertensive medication on the performance of MAP as a screening tool for PE in pregnant women with chronic hypertension or a history of gestational hypertension. Methods A retrospective study was conducted on women with chronic hypertension (N = 478) and normotensive women with a history of gestational hypertension (N = 511) who booked with the Antenatal Hypertension Clinic, Kings College Hospital, London, between 2009–2016. Blood pressure was measured repeatedly antenatally using an automated device validated for use in pregnancy and PE. The more updated International Society for the Study of Hypertension in Pregnancy (ISSHP)-2014 definition of PE was used. We constructed probit Receiver Operating Characteristic Curves (ROC) models to determine the predictive capacity of MAP in women taking anti-hypertensive medication and in those who were not. Wald tests of the null hypothesis that the two ROC curves are equal at different false-positive rates were performed. Age and medication use were taken into account in the comparisons. Results The area under the curves (AUC) for the prediction of PE (p = Conclusion The ability of MAP to predict PE and renal dysfunction is significantly improved by controlling for the use of anti-hypertensive medication in a high-risk pregnant population.

Research paper thumbnail of Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Heart (British Cardiac Society), Jan 5, 2017

Clinical drug trials in patients with heart failure and preserved ejection fraction have failed t... more Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with...

Research paper thumbnail of Cardiac Troponin Release is Associated with Biomarkers of Inflammation and Ventricular Dilatation During Critical Illness

Shock (Augusta, Ga.), Jun 29, 2016

Troponin release is common during critical illness. We hypothesized that there was an association... more Troponin release is common during critical illness. We hypothesized that there was an association between cardiac troponin T (cTnT) and biomarkers of systemic inflammation and ventricular dilatation. In an observational prospective cohort study, we enrolled consecutive adult patients admitted for non-cardiac reasons to the Intensive Care Unit (ICU) in 2 tertiary care centers. We measured cTnT, C-reactive protein (CRP), Interleukin-6 (IL-6), procalcitonin (PCT) and N-terminal pro brain natriuretic peptide (NT-proBNP) daily in the first week, and on alternate days in the second week. Using a peak cTnT cut-off ≥15ng/L and concomitant changes on electrocardiogram (ECG), patients were categorised as "definite myocardial infarction (MI)",…

Research paper thumbnail of Validation of the Withings BP-800 in pregnancy and impact of maternal characteristics on the accuracy of blood pressure measurement

Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2016

Firstly, to validate the Withings BP-800 automated device for use in pregnancy and, secondly, to ... more Firstly, to validate the Withings BP-800 automated device for use in pregnancy and, secondly, to assess the impact of maternal somatometric and demographic variables on the accuracy of the device. Prospective observational study. Kings College Hospital, London, UK. Forty-seven women of any gestation. Validation: The British Hypertension Society (BHS) Protocol (1993) was used for the validation of the Withings BP-800. Two trained observers took nine sequential same arm measurements alternating between the Withings BP-800 and the mercury sphygmomanometer. Assessment of factors affecting the disagreement between the two devices: The associations between discrepancies in the measured systolic and diastolic blood pressure by the two devices and potential predictors of discrepancy and/or possible confounders of associations including age, gestational age, ethnicity, body mass index and arm circumference were investigated using two-level mixed effects models to take into account the repeated measurements. Accuracy of the Withings BP-800 based on the grading criteria of the BHS Protocol (1993). The Withings BP-800 failed to meet the validation criteria of the BHS protocol for pregnancy and preeclampsia. Inter-device discrepancy was significantly associated with larger arm circumferences and was more pronounced with diastolic blood pressure. This relationship was independent of other maternal characteristics. The Withings BP-800 cannot be recommended for the measurement of blood pressure in pregnancy or preeclampsia. The inaccuracy of the Withings BP-800 increases when used in patients with larger arm circumferences with a propensity to over-read.

Research paper thumbnail of Virtual Touch™ Quantification to Diagnose and Monitor Liver Fibrosis in Hepatitis B and Hepatitis C: A NICE Medical Technology Guidance

Applied Health Economics and Health Policy, 2016

Virtual Touch TM Quantification (VTq) is a software application used with Siemens Acuson ultrasou... more Virtual Touch TM Quantification (VTq) is a software application used with Siemens Acuson ultrasound scanners to assess the stiffness of liver tissue. The National Institute for Health and Care Excellence (NICE) Medical Technologies Advisory Committee (MTAC) selected VTq for evaluation and invited the company to submit clinical and economic evidence. King's Technology Evaluation Centre, an External Assessment Centre (EAC) commissioned by NICE, independently assessed the evidence submitted. The EAC conducted its own systematic review, meta-analysis and economic analysis to supplement the company's submitted evidence. The meta-analyses comparing VTq and transient elastography (TE) with liver biopsy (LB) provided pooled estimates of liver stiffness and stage of fibrosis for the study populations (hepatitis B, hepatitis C or combined populations). When comparing significant fibrosis (Metavir score F C 2) for both hepatitis B and C, VTq had slightly higher values for both sensitivity and specificity (77 and 81 %) than TE (76 and 71 %). The overall prevalence of cirrhosis (F4, combined populations) was similar with VTq and TE (23 vs. 23 %), and significant fibrosis (F C 2) was lower for VTq than for TE (55 vs. 62 %). The EAC revised the company's de novo cost model, which resulted in a cost saving of £53 (against TE) and £434 (against LB). Following public consultation, taking into account submitted comments, NICE Medical Technology Guidance MTG27 was published in September 2015. This recommended the adoption of the VTq software to diagnose and monitor liver fibrosis in patients with hepatitis B or hepatitis C.

Research paper thumbnail of Assessing the relationship between chronic pain and cardiovascular disease: A systematic review and meta-analysis

Scandinavian Journal of Pain, 2016

Background and Aims Chronic pain is a potentially disabling condition affecting one in three peop... more Background and Aims Chronic pain is a potentially disabling condition affecting one in three people through impaired physical function and quality of life. While the psychosocial impact of chronic pain is already well established, little is known about the potential biological consequences. Chronic pain may be associated with an increased prevalence of cardiovascular disease, an effect that has been demonstrated across a spectrum of chronic pain conditions including low back pain, pelvic pain, neuropathic pain and fibromyalgia. The aim of this study was to review and summarize the evidence for a link between chronic pain and cardiovascular disease. We sought to clarify the nature of the relationship by examining the basis for a dose-response gradient (whereby increasing pain severity would result in greater cardiovascular disease), and by evaluating the extent to which potentially confounding variables may contribute to this association. Methods Major electronic databases MEDLINE, E...

Research paper thumbnail of Verbal Memory Decline following DBS for Parkinson's Disease: Structural Volumetric MRI Relationships

PloS one, 2016

Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is... more Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. A significant relationship was demonstrated...

Research paper thumbnail of Age Ageing-2014-Ayerbe-542-7

Research paper thumbnail of Adjusted hazard ratio of 30-d mortality of patients admitted on weekends, by ratio of registered nurses per ten beds on the weekend

Research paper thumbnail of Determinants of Mortality in Patients with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention

Cardiorenal Medicine, 2016

Background: Renal impairment is a known predictor of mortality in both the general population and... more Background: Renal impairment is a known predictor of mortality in both the general population and in patients with cardiac disease. The aim of this study was to evaluate factors that determine mortality in patients with chronic kidney disease (CKD) who have undergone percutaneous coronary intervention (PCI). Methods: In this study we included 293 consecutive patients with CKD who underwent PCI between 1st January 2007 and 30th September 2012. The primary outcome that we studied was all-cause mortality in a follow-up period of 12-69 months (mean 38.8 ± 21.7). Results: Age (p < 0.001), PCI indication (p = 0.035), CKD stage (p < 0.001) and left ventricular ejection fraction (p < 0.001) were significantly related to mortality. CKD stage 5 [hazard ratio (HR) = 6.39, 95% CI: 1.51-27.12) and severely impaired left ventricular function (HR = 4.04, 95% CI: 2.15-7.59) were the strongest predictors of mortality. Other factors tested (gender, hypertension, diabetes, hyperlipidaemia, es...

Research paper thumbnail of Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants

New England Journal of Medicine, 2016

BACKGROUND The age at which allergenic foods should be introduced into the diet of breast-fed inf... more BACKGROUND The age at which allergenic foods should be introduced into the diet of breast-fed infants is uncertain. We evaluated whether the early introduction of allergenic foods in the diet of breast-fed infants would protect against the development of food allergy. METHODS We recruited, from the general population, 1303 exclusively breast-fed infants who were 3 months of age and randomly assigned them to the early introduction of six allergenic foods (peanut, cooked egg, cow's milk, sesame, whitefish, and wheat; early-introduction group) or to the current practice recommended in the United Kingdom of exclusive breast-feeding to approximately 6 months of age (standardintroduction group). The primary outcome was food allergy to one or more of the six foods between 1 year and 3 years of age. RESULTS In the intention-to-treat analysis, food allergy to one or more of the six intervention foods developed in 7.1% of the participants in the standard-introduction group (42 of 595 participants) and in 5.6% of those in the early-introduction group (32 of 567) (P = 0.32). In the per-protocol analysis, the prevalence of any food allergy was significantly lower in the early-introduction group than in the standardintroduction group (2.4% vs. 7.3%, P = 0.01), as was the prevalence of peanut allergy (0% vs. 2.5%, P = 0.003) and egg allergy (1.4% vs. 5.5%, P = 0.009); there were no significant effects with respect to milk, sesame, fish, or wheat. The consumption of 2 g per week of peanut or egg-white protein was associated with a significantly lower prevalence of these respective allergies than was less consumption. The early introduction of all six foods was not easily achieved but was safe. CONCLUSIONS The trial did not show the efficacy of early introduction of allergenic foods in an intention-to-treat analysis. Further analysis raised the question of whether the prevention of food allergy by means of early introduction of multiple allergenic foods was dose-dependent. (Funded by the Food Standards Agency and others; EAT Current Controlled Trials number, ISRCTN14254740.

Research paper thumbnail of Azithromycin in patients with Covid-19; a systematic review and metanalysis

Background: Azithromycin (AZM) has been widely used in the management of Covid-19. However, the e... more Background: Azithromycin (AZM) has been widely used in the management of Covid-19. However, the evidence on its actual effects remains disperse and difficult to apply in clinical settings. This systematic review and metanalysis summarizes the studies on the beneficial and adverse effect of AZM in patients with Covid-19. Methods: The PRISMA 2020 statement criteria were followed. Randomized controlled trials (RCTs) and observational studies comparing clinical outcomes of patients treated, and not treated, with AZM, indexed until the 5th of July 2021, were searched in PubMed, Embase, The Web of Science, Scopus, The Cochrane Central Register of Controlled Trials, and MedRXivs. We used Random-effects models to estimate pooled effect size from aggregate data. Results: The initial search produced 4950 results. Finally, 16 studies, five RCTs and 11 with an observational design, with a total of 22984 patients, were included. The metanalysis showed no difference in mortality for those treated...

Research paper thumbnail of Evaluation of NHS Practitioner Health: capturing mental health outcomes using five instruments

BJPsych Open, 2021

Background NHS Practitioner Health is the England wide programme providing mental health and addi... more Background NHS Practitioner Health is the England wide programme providing mental health and addiction healthcare to doctors and dentists. Outcomes are assessed using five measures. Aims To contribute to a service evaluation of NHS Practitioner Health. To determine responsiveness to change and compare outcome measures. Method Measures were completed at baseline and 6 months: Generalized Anxiety Disorder Assessment (GAD-7), Perceived Stress Scale (PSS), Patient Health Questionaire-9 (PHQ-9), Warwick-Edinburgh Mental Wellbeing scale (WEMWBS), Psychological Outcome Profiles (PSYCHLOPS). Responsiveness to change was determined using effect size with improvement threshold ≥0.80. Instruments were compared using Bland–Altman plots. Results Our sample, n = 402; with 14 (3.5%) excluded for missing data; final sample, n = 388. All measures showed strong mean effect sizes: PSYCHLOPS 1.86 (95%CI 1.73–1.99), 75.8% ≥0.80; PSS 1.48 (1.34–1.62), 64.4% ≥0.80; WEMWBS 1.24 (1.13–1.35), 58.2% ≥0.80; GA...

Research paper thumbnail of The association between 7 day consultant wards and mortality risk in stroke patients admitted at the weekend

Research paper thumbnail of Effect of Iron Isomaltoside on Skeletal Muscle Energetics in Patients with Chronic Heart Failure and Iron Deficiency: The FERRIC-HF II Randomized Mechanistic Trial

Circulation

BACKGROUND Iron repletion augments exercise capacity in chronic heart failure (HF), but there is ... more BACKGROUND Iron repletion augments exercise capacity in chronic heart failure (HF), but there is a lack of mechanistic data explaining how iron could augment exercise performance despite minimal changes in hemoglobin (Hb). Besides Hb, iron is an obligate component of mitochondrial enzymes that generate cellular energy in the form of adenosine triphosphate and phosphocreatine (PCr). Dynamic phosphorus magnetic resonance spectroscopy is a noninvasive tool that quantifies in vivo muscle energetics by measuring the kinetics of PCr recovery after exertion. We tested the hypothesis that intravenous iron repletion in chronic HF enhances skeletal muscle energetics as reflected by shorter PCr recovery half-times (PCr t1/2) on phosphorus magnetic resonance spectroscopy. METHODS We enrolled 40 patients (50% anemic) with chronic HF, New York Heart Association class ≥II, left ventricular ejection fraction ≤45%, and iron deficiency (ferritin<100 μg/L or 100-300 μg/L with transferrin saturation <20%). Subjects underwent stratified (anemic versus nonanemic) randomization (1:1) to a single, double-blinded, total dose infusion of iron isomaltoside or saline placebo with end points reassessed early at 2 weeks posttreatment to minimize confounding from exercise adaptation. The primary end point was PCr t1/2 at 2 weeks. Secondary end points included ADP recovery half-time (ADP t1/2; energetic marker), iron status, symptoms, Hb, exercise capacity, and safety. RESULTS In the total population, treatment groups were similar at baseline. At 2 weeks, iron isomaltoside improved PCr t1/2 (adjusted difference, -6.8 s; 95% CI, 11.5 to -2.1; P=0.006), ADP t1/2 (-5.3 s; 95% CI, -9.7 to -0.9; P=0.02), ferritin (304 ng/mL; 95% CI, 217-391; P<0.0001), transferrin saturation (6.8%; 95% CI, 2.7-10.8; P=0.002), New York Heart Association class (-0.23; 95% CI, -0.46 to -0.01; P=0.04), resting respiratory rate (-0.7 breaths/min; 95% CI, -1.2 to -0.2; P=0.009), and postexercise Borg dyspnea score (-2.0; 95% CI, -3.7 to -0.3; P=0.04), but not Hb (2.4 g/L; 95% CI, -3.5 to 8.4; P=0.41). Adverse events were similar between groups. In subgroup analyses, iron isomaltoside improved PCr t1/2 in anemic (-8.4 s; 95% CI, -16.7 to -0.2; P=0.04) and nonanemic (-5.2 s; 95% CI, -10.6 to 0.2; P=0.06) cohorts. CONCLUSIONS In patients with chronic HF and iron deficiency, a total repletion dose of iron isomaltoside given at a single sitting is well tolerated and associated with faster skeletal muscle PCr t1/2 at 2 weeks, implying better mitochondrial function. Augmented skeletal muscle energetics might therefore be an important mechanism via which iron repletion confers benefits in chronic HF despite minimal Hb changes. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005592-13/GB . Unique identifier: EudraCT 2012-005592-13.

Research paper thumbnail of Disparities in the management of cardiovascular risk factors in patients with psychiatric disorders: a systematic review and meta-analysis

Psychological medicine, 2018

The high cardiovascular (CV) morbidity and mortality reported for patients with psychiatric disor... more The high cardiovascular (CV) morbidity and mortality reported for patients with psychiatric disorders may possibly be due to a poorer management of CV risk factors (CVRFs). However, these healthcare disparities remain poorly understood. In this paper, studies comparing the management of smoking, diabetes, hypertension and dyslipidaemia, in patients with and without depression, anxiety, schizophrenia, bipolar or personality disorder, were reviewed. Prospective studies comparing rates of screening, diagnosis, treatment and control of CVRFs were searched in PubMed, Embase, PsychInfo, Scopus and Web of Science (inception to January 2017). The Meta-analysis of Observational Studies in Epidemiology (MOOSE) criteria were used. Studies were assessed for quality. Wherever possible, meta-analyses were conducted to summarize the findings. Twenty studies, out of the 18 333 references initially identified, were included. Most studies were heterogeneous in design. Two areas permitted meta-analyse...

Research paper thumbnail of The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis

Journal of pain research, 2017

Osteoarthritis (OA) is the most prevalent arthritis worldwide and is characterized by chronic pai... more Osteoarthritis (OA) is the most prevalent arthritis worldwide and is characterized by chronic pain and impaired physical function. We hypothesized that heightened pain in hand OA could be reduced with duloxetine or pregabalin. In this prospective, randomized clinical study, we recruited 65 participants, aged 40-75 years, with a Numerical Rating Scale (NRS) for pain of at least 5. Participants were randomized to one of the following three groups: duloxetine, pregabalin, and placebo. The primary endpoint was the NRS pain score, and the secondary endpoints included the Australian and Canadian Hand Osteoarthritis Index (AUSCAN) pain, stiffness, and function scores and quantitative sensory testing by pain pressure algometry. After 13 weeks, compared to placebo, ANOVA found significant differences between the three groups (P=0.0078). In the intention-to-treat analysis, the pregabalin group showed improvement for NRS pain (P=0.023), AUSCAN pain (P=0.008), and AUSCAN function (P=0.009), but...

Research paper thumbnail of Pre-operative frailty scores as markers for assessing disability-free survival in cardiac surgery?

Journal of Cardiothoracic and Vascular Anesthesia

Research paper thumbnail of Hypertension risk and clinical care in patients with bipolar disorder or schizophrenia; a systematic review and meta-analysis

Journal of Affective Disorders

Background: A higher cardiovascular morbidity and mortality has been observed in patients with bi... more Background: A higher cardiovascular morbidity and mortality has been observed in patients with bipolar disorder (BPD) or schizophrenia, partly due to an increased risk of hypertension (HTN), or a less effective care of it. This systematic review and meta-analysis, presents a critical appraisal and summary of the studies addressing the risk of HTN, or the differences in its care, for those with schizophrenia or BPD. Methods: Prospective studies were searched in PubMed, Embase, PsycINFO, Scopus, and the Web of Science, from database inception to June 2017. A meta-analysis was undertaken to obtain pooled estimates of the risk of HTN. Results: Five studies reporting the risk of HTN, and five studies presenting differences in its clinical care, were identified. An increased risk of HTN was observed for BPD patients, with an overall Incidence Rate Ratio 1.27(1.15-1.40). The pooled Incidence Rate Ratio of HTN for those with schizophrenia was 0.94 (0.75-1.14). A poorer care of HTN (lower rates of screening, prescription, and adherence) was reported in four studies of schizophrenia, and two of BPD patients, compared to people without these conditions. Limitations: reduced number of studies on risk and care of HTN on patients with BPD or schizophrenia. Conclusions: Limited evidence suggests that patients with BPD have a higher risk of HTN. Patients with schizophrenia and BPD receive poor care of HTN. Understanding the risk of HTN, and the differences in its care, is essential for clinicians to reduce the cardiovascular morbidity and overall mortality of these patients.

Research paper thumbnail of Effects of aliskiren on mortality, cardiovascular outcomes and adverse events in patients with diabetes and cardiovascular disease or risk: A systematic review and meta-analysis of 13,395 patients

Diabetes and Vascular Disease Research

If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.

Research paper thumbnail of P 34 Does performance of mean arterial blood pressure for the screening of preeclampsia improve after controlling for the use of anti-hypertensive medication?

Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health

Question Mean arterial pressure (MAP) is a useful biomarker for the screening of preeclampsia (PE... more Question Mean arterial pressure (MAP) is a useful biomarker for the screening of preeclampsia (PE). However, MAP, a function of cardiac output and peripheral resistance, is dependent on other maternal characteristics and, for its effective use in screening, these need to be taken into account. One such characteristic is the use of anti-hypertensive medication. The aim of our study was to evaluate the impact of the use of anti-hypertensive medication on the performance of MAP as a screening tool for PE in pregnant women with chronic hypertension or a history of gestational hypertension. Methods A retrospective study was conducted on women with chronic hypertension (N = 478) and normotensive women with a history of gestational hypertension (N = 511) who booked with the Antenatal Hypertension Clinic, Kings College Hospital, London, between 2009–2016. Blood pressure was measured repeatedly antenatally using an automated device validated for use in pregnancy and PE. The more updated International Society for the Study of Hypertension in Pregnancy (ISSHP)-2014 definition of PE was used. We constructed probit Receiver Operating Characteristic Curves (ROC) models to determine the predictive capacity of MAP in women taking anti-hypertensive medication and in those who were not. Wald tests of the null hypothesis that the two ROC curves are equal at different false-positive rates were performed. Age and medication use were taken into account in the comparisons. Results The area under the curves (AUC) for the prediction of PE (p = Conclusion The ability of MAP to predict PE and renal dysfunction is significantly improved by controlling for the use of anti-hypertensive medication in a high-risk pregnant population.

Research paper thumbnail of Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Heart (British Cardiac Society), Jan 5, 2017

Clinical drug trials in patients with heart failure and preserved ejection fraction have failed t... more Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with...

Research paper thumbnail of Cardiac Troponin Release is Associated with Biomarkers of Inflammation and Ventricular Dilatation During Critical Illness

Shock (Augusta, Ga.), Jun 29, 2016

Troponin release is common during critical illness. We hypothesized that there was an association... more Troponin release is common during critical illness. We hypothesized that there was an association between cardiac troponin T (cTnT) and biomarkers of systemic inflammation and ventricular dilatation. In an observational prospective cohort study, we enrolled consecutive adult patients admitted for non-cardiac reasons to the Intensive Care Unit (ICU) in 2 tertiary care centers. We measured cTnT, C-reactive protein (CRP), Interleukin-6 (IL-6), procalcitonin (PCT) and N-terminal pro brain natriuretic peptide (NT-proBNP) daily in the first week, and on alternate days in the second week. Using a peak cTnT cut-off ≥15ng/L and concomitant changes on electrocardiogram (ECG), patients were categorised as "definite myocardial infarction (MI)",…

Research paper thumbnail of Validation of the Withings BP-800 in pregnancy and impact of maternal characteristics on the accuracy of blood pressure measurement

Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2016

Firstly, to validate the Withings BP-800 automated device for use in pregnancy and, secondly, to ... more Firstly, to validate the Withings BP-800 automated device for use in pregnancy and, secondly, to assess the impact of maternal somatometric and demographic variables on the accuracy of the device. Prospective observational study. Kings College Hospital, London, UK. Forty-seven women of any gestation. Validation: The British Hypertension Society (BHS) Protocol (1993) was used for the validation of the Withings BP-800. Two trained observers took nine sequential same arm measurements alternating between the Withings BP-800 and the mercury sphygmomanometer. Assessment of factors affecting the disagreement between the two devices: The associations between discrepancies in the measured systolic and diastolic blood pressure by the two devices and potential predictors of discrepancy and/or possible confounders of associations including age, gestational age, ethnicity, body mass index and arm circumference were investigated using two-level mixed effects models to take into account the repeated measurements. Accuracy of the Withings BP-800 based on the grading criteria of the BHS Protocol (1993). The Withings BP-800 failed to meet the validation criteria of the BHS protocol for pregnancy and preeclampsia. Inter-device discrepancy was significantly associated with larger arm circumferences and was more pronounced with diastolic blood pressure. This relationship was independent of other maternal characteristics. The Withings BP-800 cannot be recommended for the measurement of blood pressure in pregnancy or preeclampsia. The inaccuracy of the Withings BP-800 increases when used in patients with larger arm circumferences with a propensity to over-read.

Research paper thumbnail of Virtual Touch™ Quantification to Diagnose and Monitor Liver Fibrosis in Hepatitis B and Hepatitis C: A NICE Medical Technology Guidance

Applied Health Economics and Health Policy, 2016

Virtual Touch TM Quantification (VTq) is a software application used with Siemens Acuson ultrasou... more Virtual Touch TM Quantification (VTq) is a software application used with Siemens Acuson ultrasound scanners to assess the stiffness of liver tissue. The National Institute for Health and Care Excellence (NICE) Medical Technologies Advisory Committee (MTAC) selected VTq for evaluation and invited the company to submit clinical and economic evidence. King's Technology Evaluation Centre, an External Assessment Centre (EAC) commissioned by NICE, independently assessed the evidence submitted. The EAC conducted its own systematic review, meta-analysis and economic analysis to supplement the company's submitted evidence. The meta-analyses comparing VTq and transient elastography (TE) with liver biopsy (LB) provided pooled estimates of liver stiffness and stage of fibrosis for the study populations (hepatitis B, hepatitis C or combined populations). When comparing significant fibrosis (Metavir score F C 2) for both hepatitis B and C, VTq had slightly higher values for both sensitivity and specificity (77 and 81 %) than TE (76 and 71 %). The overall prevalence of cirrhosis (F4, combined populations) was similar with VTq and TE (23 vs. 23 %), and significant fibrosis (F C 2) was lower for VTq than for TE (55 vs. 62 %). The EAC revised the company's de novo cost model, which resulted in a cost saving of £53 (against TE) and £434 (against LB). Following public consultation, taking into account submitted comments, NICE Medical Technology Guidance MTG27 was published in September 2015. This recommended the adoption of the VTq software to diagnose and monitor liver fibrosis in patients with hepatitis B or hepatitis C.

Research paper thumbnail of Assessing the relationship between chronic pain and cardiovascular disease: A systematic review and meta-analysis

Scandinavian Journal of Pain, 2016

Background and Aims Chronic pain is a potentially disabling condition affecting one in three peop... more Background and Aims Chronic pain is a potentially disabling condition affecting one in three people through impaired physical function and quality of life. While the psychosocial impact of chronic pain is already well established, little is known about the potential biological consequences. Chronic pain may be associated with an increased prevalence of cardiovascular disease, an effect that has been demonstrated across a spectrum of chronic pain conditions including low back pain, pelvic pain, neuropathic pain and fibromyalgia. The aim of this study was to review and summarize the evidence for a link between chronic pain and cardiovascular disease. We sought to clarify the nature of the relationship by examining the basis for a dose-response gradient (whereby increasing pain severity would result in greater cardiovascular disease), and by evaluating the extent to which potentially confounding variables may contribute to this association. Methods Major electronic databases MEDLINE, E...

Research paper thumbnail of Verbal Memory Decline following DBS for Parkinson's Disease: Structural Volumetric MRI Relationships

PloS one, 2016

Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is... more Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. A significant relationship was demonstrated...

Research paper thumbnail of Age Ageing-2014-Ayerbe-542-7

Research paper thumbnail of Adjusted hazard ratio of 30-d mortality of patients admitted on weekends, by ratio of registered nurses per ten beds on the weekend

Research paper thumbnail of Determinants of Mortality in Patients with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention

Cardiorenal Medicine, 2016

Background: Renal impairment is a known predictor of mortality in both the general population and... more Background: Renal impairment is a known predictor of mortality in both the general population and in patients with cardiac disease. The aim of this study was to evaluate factors that determine mortality in patients with chronic kidney disease (CKD) who have undergone percutaneous coronary intervention (PCI). Methods: In this study we included 293 consecutive patients with CKD who underwent PCI between 1st January 2007 and 30th September 2012. The primary outcome that we studied was all-cause mortality in a follow-up period of 12-69 months (mean 38.8 ± 21.7). Results: Age (p < 0.001), PCI indication (p = 0.035), CKD stage (p < 0.001) and left ventricular ejection fraction (p < 0.001) were significantly related to mortality. CKD stage 5 [hazard ratio (HR) = 6.39, 95% CI: 1.51-27.12) and severely impaired left ventricular function (HR = 4.04, 95% CI: 2.15-7.59) were the strongest predictors of mortality. Other factors tested (gender, hypertension, diabetes, hyperlipidaemia, es...

Research paper thumbnail of Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants

New England Journal of Medicine, 2016

BACKGROUND The age at which allergenic foods should be introduced into the diet of breast-fed inf... more BACKGROUND The age at which allergenic foods should be introduced into the diet of breast-fed infants is uncertain. We evaluated whether the early introduction of allergenic foods in the diet of breast-fed infants would protect against the development of food allergy. METHODS We recruited, from the general population, 1303 exclusively breast-fed infants who were 3 months of age and randomly assigned them to the early introduction of six allergenic foods (peanut, cooked egg, cow's milk, sesame, whitefish, and wheat; early-introduction group) or to the current practice recommended in the United Kingdom of exclusive breast-feeding to approximately 6 months of age (standardintroduction group). The primary outcome was food allergy to one or more of the six foods between 1 year and 3 years of age. RESULTS In the intention-to-treat analysis, food allergy to one or more of the six intervention foods developed in 7.1% of the participants in the standard-introduction group (42 of 595 participants) and in 5.6% of those in the early-introduction group (32 of 567) (P = 0.32). In the per-protocol analysis, the prevalence of any food allergy was significantly lower in the early-introduction group than in the standardintroduction group (2.4% vs. 7.3%, P = 0.01), as was the prevalence of peanut allergy (0% vs. 2.5%, P = 0.003) and egg allergy (1.4% vs. 5.5%, P = 0.009); there were no significant effects with respect to milk, sesame, fish, or wheat. The consumption of 2 g per week of peanut or egg-white protein was associated with a significantly lower prevalence of these respective allergies than was less consumption. The early introduction of all six foods was not easily achieved but was safe. CONCLUSIONS The trial did not show the efficacy of early introduction of allergenic foods in an intention-to-treat analysis. Further analysis raised the question of whether the prevention of food allergy by means of early introduction of multiple allergenic foods was dose-dependent. (Funded by the Food Standards Agency and others; EAT Current Controlled Trials number, ISRCTN14254740.