The 70 kDa and 90 kDa heat shock proteins Hsp70 and Hsp90 are two abundant and highly conserved A... more The 70 kDa and 90 kDa heat shock proteins Hsp70 and Hsp90 are two abundant and highly conserved ATP-dependent molecular chaperones that participate in the maintenance of cellular homeostasis. In Escherichia coli, Hsp90 (Hsp90Ec) and Hsp70 (DnaK) directly interact and collaborate in protein remodeling. Previous work has produced a model of the direct interaction of both chaperones. The locations of the residues involved have been confirmed and the model has been validated. In this study, we investigate the allosteric communication between Hsp90Ec and DnaK and how the chaperones couple their conformational cycles. Using elastic network models (ENM), normal mode analysis (NMA), and a structural perturbation method (SPM) of asymmetric and symmetric DnaK-Hsp90Ec, we extract biologically relevant vibrations and identify residues involved in allosteric signaling. When one DnaK is bound, the dominant normal modes favor biological motions that orient a substrate protein bound to DnaK within ...
Reliance on government-led policies have heightened during the COVID-19 pandemic. Further researc... more Reliance on government-led policies have heightened during the COVID-19 pandemic. Further research on the policies associated with outcomes other than mortality rates remains warranted. We aimed to determine associations between government public health policies on the severity of the COVID-19 pandemic. This ecological study including countries reporting ≥25 daily COVID-related deaths until end May 2020, utilised public data on policy indicators described by the Blavatnik school of Government. Associations between policy indicators and severity of the pandemic (mean mortality rate, time to peak, peak deaths per 100,000, cumulative deaths after peak per 100,000 and ratio of mean slope of the descending curve to mean slope of the ascending curve) were measured using Spearman rank-order tests. Analyses were stratified for age, income and region. Among 22 countries, containment policies such as school closures appeared effective in younger populations (rs = −0.620, p = 0.042) and debt/c...
BackgroundThe COVID-19 pandemic has placed significant pressure on health and social care. Surviv... more BackgroundThe COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19.MethodsPatients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease.ResultsThirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years...
Patient Reported Outcome Measures (PROMs) assess clinical outcomes from the perspective of the pa... more Patient Reported Outcome Measures (PROMs) assess clinical outcomes from the perspective of the patient. The stroke community recommended fifteen questions for use in stroke survivors, based on the established PROMIS10 with five additional stroke-specific questions. This study aimed to determine its association with the National Institute of Health Stroke Scale (NIHSS) on admission. PROM responses were taken from an existing randomised control trial and, using secondary analysis, the total score was calculated out of 100. The association between PROMs and NIHSS was estimated. Using a multivariable regression, an adjusted mean difference (aMD) in PROM total score for the baseline clinical characteristics was calculated. 343 participants (16.3%) completed the PROM; mean age 71.7 (30–94) years; 133 women (38.8%). There was a strong association between increasing NIHSS Scores on admission to hospital and worsening PROM scores at 6 months (p = 0.002). There was consistency between the NIH...
Frailty assessed using Clinical Frailty Scale (CFS) is a good predictor of adverse clinical event... more Frailty assessed using Clinical Frailty Scale (CFS) is a good predictor of adverse clinical events including mortality in older people. CFS is also an essential criterion for determining ceilings of care in people with COVID-19. Our aims were to assess the prevalence of frailty in older patients hospitalised with COVID-19, their sex and age distribution, and the completion rate of the CFS tool in evaluating frailty. Methods: Data were collected from thirteen sites. CFS was assessed routinely at the time of admission to hospital and ranged from 1 (very fit) to 9 (terminally ill). The completion rate of the CFS was assessed. The presence of major comorbidities such as diabetes and cardiovascular disease was noted. Results: A total of 1277 older patients with COVID-19, aged ≥ 65 (79.9 ± 8.1) years were included in the study, with 98.5% having fully completed CFS. The total prevalence of frailty (CFS ≥ 5) was 66.9%, being higher in women than men (75.2% vs. 59.4%, p < 0.001). Frailty...
Background: In a large UK study we investigated the relationship between smartphone addiction and... more Background: In a large UK study we investigated the relationship between smartphone addiction and sleep quality in a young adult population.Methods: We undertook a large UK cross-sectional observational study of 1,043 participants aged 18 to 30 between January 21st and February 30th 2019. Participants completed the Smartphone Addiction Scale Short Version, an adapted Pittsburgh Sleep Quality Score Index and reported smartphone use reduction strategies using both in-person (n = 968) and online (n = 75) questionnaires. A crude and adjusted logistic regression was fitted to assess risk factors for smartphone addiction, and the association between smartphone addiction and poor sleep.Results: One thousand seventy one questionnaires were returned, of which 1,043 participants were included, with median age 21.1 [interquartile range (IQR) 19–22]. Seven hundred and sixty three (73.2%) were female, and 406 reported smartphone addiction (38.9%). A large proportion of participants disclosed poo...
Coronavirus disease 2019 (COVID-19) infection causes acute lung injury, resulting from aggressive... more Coronavirus disease 2019 (COVID-19) infection causes acute lung injury, resulting from aggressive inflammation initiated by viral replication. There has been much speculation about the potential role of non-steroidal inflammatory drugs (NSAIDs), which increase the expression of angiotensin-converting enzyme 2 (ACE2), a binding target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the host cell, which could lead to poorer outcomes in COVID-19 disease. The aim of this study was to examine the association between routine use of NSAIDs and outcomes in hospitalised patients with COVID-19. This was a multicentre, observational study, with data collected from adult patients with COVID-19 admitted to eight UK hospitals. Of 1222 patients eligible to be included, 54 (4.4%) were routinely prescribed NSAIDs prior to admission. Univariate results suggested a modest protective effect from the use of NSAIDs, but in the multivariable analysis, there was no association bet...
Background Knowledge of the prevalence of morbidity secondary to stroke is important for health c... more Background Knowledge of the prevalence of morbidity secondary to stroke is important for health care professionals, health care commissioners, third sector organizations, and stroke survivors to understand the likely progress of poststroke sequelae and to aid in commissioning decisions, planning care, and adjusting to life after stroke. Objective The primary aim of the Morbidity PRevalence Estimate In StrokE (MORe PREcISE) study is to determine the prevalence of morbidity secondary to a stroke, predictors of morbidity, and trends in quality of life and functional status using patient-reported outcomes, cognitive and functional assessments. Methods A total of 500 participants will be recruited across Wales and England within 14 days following an admission to a stroke unit for either an ischemic or hemorrhagic stroke as part of a multicenter cohort study. Participants are assessed at baseline ≤14 days poststroke and subsequently at 90 (± 14) days and 180 (± 14) days poststroke. At eac...
Background Over the past decade, smartphone use has become widespread amongst today’s children an... more Background Over the past decade, smartphone use has become widespread amongst today’s children and young people (CYP) which parallels increases in poor mental health in this group. Simultaneously, media concern abounds about the existence of ‘smartphone addiction’ or problematic smartphone use. There has been much recent research concerning the prevalence of problematic smartphone use is in children and young people who use smartphones, and how this syndrome relates to mental health outcomes, but this has not been synthesized and critically evaluated. Aims To conduct a systematic review and meta-analysis to examine the prevalence of PSU and quantify the association with mental health harms. Methods A search strategy using Medical Subject Headings was developed and adapted for eight databases between January 1, 1st 2011 to October 15th 2017. No language restriction was applied. Of 924 studies identified, 41 were included in this review, three of which were cohort studies and 38 were ...
ObjectiveTo estimate the comparative clinical efficacy and acceptability of non-surgical brain st... more ObjectiveTo estimate the comparative clinical efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults.DesignSystematic review with pairwise and network meta-analysis.Data sourcesElectronic search of Embase, PubMed/Medline, and PsycINFO up to 8 May 2018, supplemented by manual searches of bibliographies of several reviews (published between 2009 and 2018) and included trials.Eligibility criteria for selecting studiesClinical trials with random allocation to electroconvulsive therapy (ECT), transcranial magnetic stimulation (repetitive (rTMS), accelerated, priming, deep, and synchronised), theta burst stimulation, magnetic seizure therapy, transcranial direct current stimulation (tDCS), or sham therapy.Main outcome measuresPrimary outcomes were response (efficacy) and all cause discontinuation (discontinuation of treatment for any reason) (acceptability), presented as odds ratios with 95% confidence intervals. Remissi...
Cancer survival rates in the UK are lower in comparison with similar countries in Europe and this... more Cancer survival rates in the UK are lower in comparison with similar countries in Europe and this may be linked to socioeconomic inequalities in stage of cancer diagnosis and survival. Targeted cancer awareness interventions have the potential to improve earlier symptomatic diagnosis and reduce socioeconomic inequalities in cancer outcomes. The health check is an innovative, theory-based intervention designed to increase awareness of cancer symptoms and risk factors, and encourage timely help seeking among adults living in deprived communities. A prospective, non-randomised evaluation was undertaken to test the feasibility and acceptability of the health check for adults aged 40 years and over living in deprived areas of Wales. Primary outcomes included recruitment and retention of approximately 100 adults, reach to participants in the lowest deprivation quartile, and intervention acceptability. Secondary outcomes included self-reported cancer symptom recognition, help-seeking behav...
to investigate the prevalence and impact of frailty for general surgical patients. we conducted a... more to investigate the prevalence and impact of frailty for general surgical patients. we conducted a systematic review and meta-analysis. Studies published between 1 January 1980 and 31 August 2017 were searched from seven databases. Incidence of clinical outcomes (mortality at Days 30 and 90; readmission at Day 30, surgical complications and length of stay) were estimated by frailty subgroup (not-frail, pre-frail and frail). 2,281 participants from nine observational studies were included, 49.3% (1013/2055) were males. Mean age ranged from 61 to 77 years old. Eight studies provided outcome data and were quality assessed and of fair or good quality, and one study only provided an estimate of prevalence and was not quality assessed. The prevalence estimate ranged between 31.3 and 45.8% for pre-frailty, and 10.4 and 37.0% for frailty. After pooling, Day 30 mortality was 8% (95% CI: 4-12%; I2 = 0%) for frail compared to 1% for non-frail patients (95% CI: 0-2%; I2 = 75%). Due to heterogene...
Treatment options for severe, enduring anorexia nervosa (SE-AN) are limited. Non-invasive neuromo... more Treatment options for severe, enduring anorexia nervosa (SE-AN) are limited. Non-invasive neuromodulation is a promising emerging intervention. Our study is a feasibility randomised controlled trial of repetitive transcranial magnetic stimulation (rTMS) in individuals with SE-AN, which aims to inform the design of a future large-scale trial. Double-blind, parallel group, two-arm, sham-controlled trial. Specialist eating disorders centre. Community-dwelling people with anorexia nervosa, an illness duration of ≥3 years and at least one previous completed treatment. Participants received 20 sessions (administered over 4 weeks) of MRI-guided real or sham high-frequency rTMS to the left dorsolateral prefrontal cortex in addition to treatment-as-usual. Primary outcomes were recruitment, attendance and retention rates. Secondary outcomes included body mass index (BMI), eating disorder symptoms, mood, quality of life and rTMS safety and tolerability. Assessments were conducted at baseline, ...
The 70 kDa and 90 kDa heat shock proteins Hsp70 and Hsp90 are two abundant and highly conserved A... more The 70 kDa and 90 kDa heat shock proteins Hsp70 and Hsp90 are two abundant and highly conserved ATP-dependent molecular chaperones that participate in the maintenance of cellular homeostasis. In Escherichia coli, Hsp90 (Hsp90Ec) and Hsp70 (DnaK) directly interact and collaborate in protein remodeling. Previous work has produced a model of the direct interaction of both chaperones. The locations of the residues involved have been confirmed and the model has been validated. In this study, we investigate the allosteric communication between Hsp90Ec and DnaK and how the chaperones couple their conformational cycles. Using elastic network models (ENM), normal mode analysis (NMA), and a structural perturbation method (SPM) of asymmetric and symmetric DnaK-Hsp90Ec, we extract biologically relevant vibrations and identify residues involved in allosteric signaling. When one DnaK is bound, the dominant normal modes favor biological motions that orient a substrate protein bound to DnaK within ...
Reliance on government-led policies have heightened during the COVID-19 pandemic. Further researc... more Reliance on government-led policies have heightened during the COVID-19 pandemic. Further research on the policies associated with outcomes other than mortality rates remains warranted. We aimed to determine associations between government public health policies on the severity of the COVID-19 pandemic. This ecological study including countries reporting ≥25 daily COVID-related deaths until end May 2020, utilised public data on policy indicators described by the Blavatnik school of Government. Associations between policy indicators and severity of the pandemic (mean mortality rate, time to peak, peak deaths per 100,000, cumulative deaths after peak per 100,000 and ratio of mean slope of the descending curve to mean slope of the ascending curve) were measured using Spearman rank-order tests. Analyses were stratified for age, income and region. Among 22 countries, containment policies such as school closures appeared effective in younger populations (rs = −0.620, p = 0.042) and debt/c...
BackgroundThe COVID-19 pandemic has placed significant pressure on health and social care. Surviv... more BackgroundThe COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19.MethodsPatients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease.ResultsThirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years...
Patient Reported Outcome Measures (PROMs) assess clinical outcomes from the perspective of the pa... more Patient Reported Outcome Measures (PROMs) assess clinical outcomes from the perspective of the patient. The stroke community recommended fifteen questions for use in stroke survivors, based on the established PROMIS10 with five additional stroke-specific questions. This study aimed to determine its association with the National Institute of Health Stroke Scale (NIHSS) on admission. PROM responses were taken from an existing randomised control trial and, using secondary analysis, the total score was calculated out of 100. The association between PROMs and NIHSS was estimated. Using a multivariable regression, an adjusted mean difference (aMD) in PROM total score for the baseline clinical characteristics was calculated. 343 participants (16.3%) completed the PROM; mean age 71.7 (30–94) years; 133 women (38.8%). There was a strong association between increasing NIHSS Scores on admission to hospital and worsening PROM scores at 6 months (p = 0.002). There was consistency between the NIH...
Frailty assessed using Clinical Frailty Scale (CFS) is a good predictor of adverse clinical event... more Frailty assessed using Clinical Frailty Scale (CFS) is a good predictor of adverse clinical events including mortality in older people. CFS is also an essential criterion for determining ceilings of care in people with COVID-19. Our aims were to assess the prevalence of frailty in older patients hospitalised with COVID-19, their sex and age distribution, and the completion rate of the CFS tool in evaluating frailty. Methods: Data were collected from thirteen sites. CFS was assessed routinely at the time of admission to hospital and ranged from 1 (very fit) to 9 (terminally ill). The completion rate of the CFS was assessed. The presence of major comorbidities such as diabetes and cardiovascular disease was noted. Results: A total of 1277 older patients with COVID-19, aged ≥ 65 (79.9 ± 8.1) years were included in the study, with 98.5% having fully completed CFS. The total prevalence of frailty (CFS ≥ 5) was 66.9%, being higher in women than men (75.2% vs. 59.4%, p < 0.001). Frailty...
Background: In a large UK study we investigated the relationship between smartphone addiction and... more Background: In a large UK study we investigated the relationship between smartphone addiction and sleep quality in a young adult population.Methods: We undertook a large UK cross-sectional observational study of 1,043 participants aged 18 to 30 between January 21st and February 30th 2019. Participants completed the Smartphone Addiction Scale Short Version, an adapted Pittsburgh Sleep Quality Score Index and reported smartphone use reduction strategies using both in-person (n = 968) and online (n = 75) questionnaires. A crude and adjusted logistic regression was fitted to assess risk factors for smartphone addiction, and the association between smartphone addiction and poor sleep.Results: One thousand seventy one questionnaires were returned, of which 1,043 participants were included, with median age 21.1 [interquartile range (IQR) 19–22]. Seven hundred and sixty three (73.2%) were female, and 406 reported smartphone addiction (38.9%). A large proportion of participants disclosed poo...
Coronavirus disease 2019 (COVID-19) infection causes acute lung injury, resulting from aggressive... more Coronavirus disease 2019 (COVID-19) infection causes acute lung injury, resulting from aggressive inflammation initiated by viral replication. There has been much speculation about the potential role of non-steroidal inflammatory drugs (NSAIDs), which increase the expression of angiotensin-converting enzyme 2 (ACE2), a binding target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the host cell, which could lead to poorer outcomes in COVID-19 disease. The aim of this study was to examine the association between routine use of NSAIDs and outcomes in hospitalised patients with COVID-19. This was a multicentre, observational study, with data collected from adult patients with COVID-19 admitted to eight UK hospitals. Of 1222 patients eligible to be included, 54 (4.4%) were routinely prescribed NSAIDs prior to admission. Univariate results suggested a modest protective effect from the use of NSAIDs, but in the multivariable analysis, there was no association bet...
Background Knowledge of the prevalence of morbidity secondary to stroke is important for health c... more Background Knowledge of the prevalence of morbidity secondary to stroke is important for health care professionals, health care commissioners, third sector organizations, and stroke survivors to understand the likely progress of poststroke sequelae and to aid in commissioning decisions, planning care, and adjusting to life after stroke. Objective The primary aim of the Morbidity PRevalence Estimate In StrokE (MORe PREcISE) study is to determine the prevalence of morbidity secondary to a stroke, predictors of morbidity, and trends in quality of life and functional status using patient-reported outcomes, cognitive and functional assessments. Methods A total of 500 participants will be recruited across Wales and England within 14 days following an admission to a stroke unit for either an ischemic or hemorrhagic stroke as part of a multicenter cohort study. Participants are assessed at baseline ≤14 days poststroke and subsequently at 90 (± 14) days and 180 (± 14) days poststroke. At eac...
Background Over the past decade, smartphone use has become widespread amongst today’s children an... more Background Over the past decade, smartphone use has become widespread amongst today’s children and young people (CYP) which parallels increases in poor mental health in this group. Simultaneously, media concern abounds about the existence of ‘smartphone addiction’ or problematic smartphone use. There has been much recent research concerning the prevalence of problematic smartphone use is in children and young people who use smartphones, and how this syndrome relates to mental health outcomes, but this has not been synthesized and critically evaluated. Aims To conduct a systematic review and meta-analysis to examine the prevalence of PSU and quantify the association with mental health harms. Methods A search strategy using Medical Subject Headings was developed and adapted for eight databases between January 1, 1st 2011 to October 15th 2017. No language restriction was applied. Of 924 studies identified, 41 were included in this review, three of which were cohort studies and 38 were ...
ObjectiveTo estimate the comparative clinical efficacy and acceptability of non-surgical brain st... more ObjectiveTo estimate the comparative clinical efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults.DesignSystematic review with pairwise and network meta-analysis.Data sourcesElectronic search of Embase, PubMed/Medline, and PsycINFO up to 8 May 2018, supplemented by manual searches of bibliographies of several reviews (published between 2009 and 2018) and included trials.Eligibility criteria for selecting studiesClinical trials with random allocation to electroconvulsive therapy (ECT), transcranial magnetic stimulation (repetitive (rTMS), accelerated, priming, deep, and synchronised), theta burst stimulation, magnetic seizure therapy, transcranial direct current stimulation (tDCS), or sham therapy.Main outcome measuresPrimary outcomes were response (efficacy) and all cause discontinuation (discontinuation of treatment for any reason) (acceptability), presented as odds ratios with 95% confidence intervals. Remissi...
Cancer survival rates in the UK are lower in comparison with similar countries in Europe and this... more Cancer survival rates in the UK are lower in comparison with similar countries in Europe and this may be linked to socioeconomic inequalities in stage of cancer diagnosis and survival. Targeted cancer awareness interventions have the potential to improve earlier symptomatic diagnosis and reduce socioeconomic inequalities in cancer outcomes. The health check is an innovative, theory-based intervention designed to increase awareness of cancer symptoms and risk factors, and encourage timely help seeking among adults living in deprived communities. A prospective, non-randomised evaluation was undertaken to test the feasibility and acceptability of the health check for adults aged 40 years and over living in deprived areas of Wales. Primary outcomes included recruitment and retention of approximately 100 adults, reach to participants in the lowest deprivation quartile, and intervention acceptability. Secondary outcomes included self-reported cancer symptom recognition, help-seeking behav...
to investigate the prevalence and impact of frailty for general surgical patients. we conducted a... more to investigate the prevalence and impact of frailty for general surgical patients. we conducted a systematic review and meta-analysis. Studies published between 1 January 1980 and 31 August 2017 were searched from seven databases. Incidence of clinical outcomes (mortality at Days 30 and 90; readmission at Day 30, surgical complications and length of stay) were estimated by frailty subgroup (not-frail, pre-frail and frail). 2,281 participants from nine observational studies were included, 49.3% (1013/2055) were males. Mean age ranged from 61 to 77 years old. Eight studies provided outcome data and were quality assessed and of fair or good quality, and one study only provided an estimate of prevalence and was not quality assessed. The prevalence estimate ranged between 31.3 and 45.8% for pre-frailty, and 10.4 and 37.0% for frailty. After pooling, Day 30 mortality was 8% (95% CI: 4-12%; I2 = 0%) for frail compared to 1% for non-frail patients (95% CI: 0-2%; I2 = 75%). Due to heterogene...
Treatment options for severe, enduring anorexia nervosa (SE-AN) are limited. Non-invasive neuromo... more Treatment options for severe, enduring anorexia nervosa (SE-AN) are limited. Non-invasive neuromodulation is a promising emerging intervention. Our study is a feasibility randomised controlled trial of repetitive transcranial magnetic stimulation (rTMS) in individuals with SE-AN, which aims to inform the design of a future large-scale trial. Double-blind, parallel group, two-arm, sham-controlled trial. Specialist eating disorders centre. Community-dwelling people with anorexia nervosa, an illness duration of ≥3 years and at least one previous completed treatment. Participants received 20 sessions (administered over 4 weeks) of MRI-guided real or sham high-frequency rTMS to the left dorsolateral prefrontal cortex in addition to treatment-as-usual. Primary outcomes were recruitment, attendance and retention rates. Secondary outcomes included body mass index (BMI), eating disorder symptoms, mood, quality of life and rTMS safety and tolerability. Assessments were conducted at baseline, ...
Uploads
Papers by Ben Carter