Publications by authors named "Claudia-Martina Messow"

35 Publications

Randomized Trial-PrEscription of intraDialytic exercise to improve quAlity of Life in Patients Receiving Hemodialysis.

Kidney Int Rep 2021 Aug 30;6(8):2159-2170. Epub 2021 May 30.

School of Health Sciences, Queen Margaret University, Edinburgh, UK.

Introduction: Whether clinically implementable exercise interventions in people receiving hemodialysis (HD) therapy improve health-related quality of life (HRQoL) remains unknown. The PrEscription of intraDialytic exercise to improve quAlity of Life PEDAL) study evaluated the clinical benefit and cost-effectiveness of a 6-month intradialytic exercise program.

Methods: In a multicenter, single-blinded, randomized, controlled trial, people receiving HD were randomly assigned to (i) intradialytic exercise training (exercise intervention group [EX]) and (ii) usual care (control group [CON]). Primary outcome was change in Kidney Disease Quality of Life Short-Form Physical Component Summary (KDQOL-SF 1.3 PCS) from baseline to 6 months. Cost-effectiveness was determined using health economic analysis; physiological impairment was evaluated by peak oxygen uptake; and harms were recorded.

Results: We randomized 379 participants; 335 and 243 patients (EX  = 127; CON  = 116) completed baseline and 6-month assessments, respectively. Mean difference in change PCS from baseline to 6 months between EX and CON was 2.4 (95% confidence interval [CI]: -0.1 to 4.8) arbitrary units ( = 0.055); no improvements were observed in peak oxygen uptake or secondary outcome measures. Participants in the intervention group had poor compliance (47%) and poor adherence (18%) to the exercise prescription. Cost of delivering intervention ranged from US$598 to US$1092 per participant per year. The number of participants with harms was similar between EX ( = 69) and CON ( = 56). A primary limitation was the lack of an attention CON. Many patients also withdrew from the study or were too unwell to complete all physiological outcome assessments.

Conclusions: A 6-month intradialytic aerobic exercise program was not clinically beneficial in improving HRQoL as delivered to this cohort of deconditioned patients on HD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ekir.2021.05.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343798PMC
August 2021

Exercise programme to improve quality of life for patients with end-stage kidney disease receiving haemodialysis: the PEDAL RCT.

Health Technol Assess 2021 Jun;25(40):1-52

School of Health Sciences, Queen Margaret University, Edinburgh, UK.

Background: Whether or not clinically implementable exercise interventions in haemodialysis patients improve quality of life remains unknown.

Objectives: The PEDAL (PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease) trial evaluated the clinical effectiveness and cost-effectiveness of a 6-month intradialytic exercise programme on quality of life compared with usual care for haemodialysis patients.

Design: We conducted a prospective, multicentre randomised controlled trial of haemodialysis patients from five haemodialysis centres in the UK and randomly assigned them (1 : 1) using a web-based system to (1) intradialytic exercise training plus usual-care maintenance haemodialysis or (2) usual-care maintenance haemodialysis.

Setting: The setting was five dialysis units across the UK from 2015 to 2019.

Participants: The participants were adult patients with end-stage kidney disease who had been receiving haemodialysis therapy for > 1 year.

Interventions: Participants were randomised to receive usual-care maintenance haemodialysis or usual-care maintenance haemodialysis plus intradialytic exercise training.

Main Outcome Measures: The primary outcome of the study was change in Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score (from baseline to 6 months). Cost-effectiveness was determined using health economic analysis and the EuroQol-5 Dimensions, five-level version. Additional secondary outcomes included quality of life (Kidney Disease Quality of Life Short Form, version 1.3, generic multi-item and burden of kidney disease scales), functional capacity (sit-to-stand 60 and 10-metre Timed Up and Go tests), physiological measures (peak oxygen uptake and arterial stiffness), habitual physical activity levels (measured by the International Physical Activity Questionnaire and Duke Activity Status Index), fear of falling (measured by the Tinetti Falls Efficacy Scale), anthropometric measures (body mass index and waist circumference), clinical measures (including medication use, resting blood pressure, routine biochemistry, hospitalisations) and harms associated with intervention. A nested qualitative study was conducted.

Results: We randomised 379 participants; 335 patients completed baseline assessments and 243 patients (intervention,  = 127; control,  = 116) completed 6-month assessments. The mean difference in change in physical component summary score from baseline to 6 months between the intervention group and control group was 2.4 arbitrary units (95% confidence interval -0.1 to 4.8 arbitrary units;  = 0.055). Participants in the intervention group had poor compliance (49%) and very poor adherence (18%) to the exercise prescription. The cost of delivering the intervention ranged from £463 to £848 per participant per year. The number of participants with harms was similar in the intervention ( = 69) and control ( = 56) groups.

Limitations: Participants could not be blinded to the intervention; however, outcome assessors were blinded to group allocation.

Conclusions: On trial completion the primary outcome (Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score) was not statistically improved compared with usual care. The findings suggest that implementation of an intradialytic cycling programme is not an effective intervention to enhance health-related quality of life, as delivered to this cohort of deconditioned patients receiving haemodialysis.

Future Work: The benefits of longer interventions, including progressive resistance training, should be confirmed even if extradialytic delivery is required. Future studies also need to evaluate whether or not there are subgroups of patients who may benefit from this type of intervention, and whether or not there is scope to optimise the exercise intervention to improve compliance and clinical effectiveness.

Trial Registration: Current Controlled Trials ISRCTN83508514.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 40. See the NIHR Journals Library website for further project information.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3310/hta25400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256322PMC
June 2021

The PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease trial: study design and baseline data for a multicentre randomized controlled trial.

Clin Kidney J 2021 May 10;14(5):1345-1355. Epub 2020 Sep 10.

School of Health Sciences, Centre for Health, Activity and Rehabilitation Research, Queen Margaret University, Edinburgh, UK.

Background: Exercise interventions designed to improve physical function and reduce sedentary behaviour in haemodialysis (HD) patients might improve exercise capacity, reduce fatigue and lead to improved quality of life (QOL). The PrEscription of intraDialytic exercise to improve quAlity of Life study aimed to evaluate the effectiveness of a 6-month intradialytic exercise programme on QOL and physical function, compared with usual care for patients on HD in the UK.

Methods: We conducted a prospective, pragmatic multicentre randomized controlled trial in 335 HD patients and randomly (1:1) assigned them to either (i) intradialytic exercise training plus usual care maintenance HD or (ii) usual care maintenance HD. The primary outcome of the study was the change in Kidney Disease Quality of Life Short Form (KDQOL-SF 1.3) Physical Component Score between baseline and 6 months. Additional secondary outcomes included changes in peak aerobic capacity, physical fitness, habitual physical activity levels and falls (International Physical Activity Questionnaire, Duke's Activity Status Index and Tinetti Falls Efficacy Scale), QOL and symptom burden assessments (EQ5D), arterial stiffness (pulse wave velocity), anthropometric measures, resting blood pressure, clinical chemistry, safety and harms associated with the intervention, hospitalizations and cost-effectiveness. A nested qualitative study investigated the experience and acceptability of the intervention for both participants and members of the renal health care team.

Results: At baseline assessment, 62.4% of the randomized cohort were male, the median age was 59.3 years and 50.4% were white. Prior cerebrovascular events and myocardial infarction were present in 8 and 12% of the cohort, respectively, 77.9% of patients had hypertension and 39.4% had diabetes. Baseline clinical characteristics and laboratory data for the randomized cohort were generally concordant with data from the UK Renal Registry.

Conclusion: The results from this study will address a significant knowledge gap in the prescription of exercise interventions for patients receiving maintenance HD therapy and inform the development of intradialytic exercise programmes both nationally and internationally.

Trial Registration: ISRCTN N83508514; registered on 17 December 2014.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ckj/sfaa107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087141PMC
May 2021

Periodontal therapy and treatment of hypertension-alternative to the pharmacological approach. A systematic review and meta-analysis.

Pharmacol Res 2021 04 19;166:105511. Epub 2021 Feb 19.

Oral Sciences Research Group, Glasgow Dental Hospital and School, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK; Department of Experimental Dentistry and Dental Prophylaxis, Jagiellonian University, Krakow, Poland. Electronic address:

Aim: Quantitative comparison of the effects of intensive (IPT) or conventional (CPT) periodontal treatment on arterial blood pressure, endothelial function and inflammatory/metabolic biomarkers.

Materials And Methods: A systematic search was conducted to identify randomized controlled trials (RCT) of IPT (supra and subgingival instrumentation). Eight RCTs were included in the meta-analysis. Difference in change of systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and after IPT or CPT were the primary outcomes. The secondary outcomes included: endothelial function and selected inflammatory/anti-inflammatory (CRP, IL-6, IL-10, IFN-γ) and metabolic biomarkers (HDL, LDL, TGs).

Results: The overall effect estimates (pooled Weighted Mean Difference (WMD)) of the primary outcome for SBP and DBP was -4.3 mmHg [95%CI: -9.10-0.48], p = 0.08 and -3.16 mmHg [95%CI: -6.51-0.19], p = 0.06 respectively. These studies were characterized by high heterogeneity. Therefore, random effects model for meta-analysis was performed. Sub-group analyses confirmed statistically significant reduction in SBP [WMD = -11.41 mmHg (95%CI: -13.66, -9.15) P < 0.00001] and DBP [WMD = -8.43 mmHg (95%CI: -10.96,-5.91)P < 0.00001] after IPT vs CPT among prehypertensive/hypertensive patients, while this was not observed in normotensive individuals. The meta-analyses showed significant reductions in CRP and improvement of endothelial function following IPT at all analysed timepoints.

Conclusions: IPT leads to improvement of the cardiovascular health in hypertensive and prehypertensive individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2021.105511DOI Listing
April 2021

Study protocol for COVID-RV: a multicentre prospective observational cohort study of right ventricular dysfunction in ventilated patients with COVID-19.

BMJ Open 2021 01 13;11(1):e042098. Epub 2021 Jan 13.

Academic Unit of Anaesthesia, Pain and Critical Care Medicine, University of Glasgow, Glasgow, UK

Introduction: COVID-19 can cause severe acute respiratory failure requiring management in intensive care unit with invasive ventilation and a 40% mortality rate. Cardiovascular manifestations are common and studies have shown an increase in right ventricular (RV) dysfunction associated with mortality. These studies, however, comprise heterogeneous patient groups with few requiring invasive ventilation. This study will investigate the prevalence and prognostic significance of RV dysfunction in ventilated patients with COVID-19 which may lead to targeted interventions to improve patient outcomes.

Methods And Analysis: This prospective multicentre observational cohort study will perform transthoracic echocardiography (TTE) in 150 patients with COVID-19 requiring invasive ventilation for more than 48 hours. RV dysfunction will be defined as TTE evidence of RV dilatation along with the presence of septal flattening. Baseline demographics, disease severity data and clinical information relating to proposed aetiological mechanisms of RV dysfunction (acute respiratory distress syndrome (ARDS), disordered coagulation, direct myocardial injury and ventilation) will be collected and analysed.Primary outcome measures include the prevalence of RV dysfunction and its association with 30-day mortality. Exploratory outcome measures will investigate the association of the proposed aetiological mechanisms of RV dysfunction to the primary outcomes.Prevalence of RV dysfunction will be determined along with 95% Clopper-Pearson CIs and 30-day survival will be analysed using logistic regression adjusting for patient demographics, phase of disease and baseline severity of illness. The role of potential aetiological factors (ARDS, disordered coagulation, direct myocardial injury and ventilation) in relation to the primary outcomes will be analysed using logistic regression.

Ethics And Dissemination: Approval was gained from Scotland A Research Ethics Committee (REC reference 20/SS/0059). Findings will be disseminated by various methods including webinars, international presentations and publication in peer-reviewed journals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-042098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811959PMC
January 2021

Brief formula low-energy-diet for relapse management during weight loss maintenance in the Diabetes Remission Clinical Trial (DiRECT).

J Hum Nutr Diet 2021 06 6;34(3):472-479. Epub 2021 Jan 6.

Human Nutrition, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK.

Background: Weight loss maintenance (WLM) is critical for sustaining type 2 diabetes (T2D) remission, but poorly evidenced. We evaluated brief return to formula low-energy-diet (LED) as relapse treatments (RTs) during the WLM phase of the Diabetes Remission Clinical Trial (DiRECT).

Methods: This post-hoc evaluation included all participants commencing the WLM phase of DiRECT. The protocol offered RT when regain of >2 kg occurred.

Results: In total, 123/149 (83%) DiRECT intervention participants commenced the WLM phase after 26 (17%) had withdrawn prior to the WLM phase. Most participants [99/123 (80%)] regained >2 kg during the WLM phase, among whom 60/99 (61%) were recorded as using RT and 39/99 (39%) not using any RT. At baseline, RT users had a higher mean (SD) body mass index [35.8 (4.9) kg m vs. 33.8 (3.9) kg m , p = 0.0231] and had greater social deprivation (P = 0.0003) than non-users, although otherwise the groups were similar. Weight loss ≥ 2k g was achieved in 30/93 (32%) of RT attempts. At 2 years, those regaining >2 kg and using RT (n = 60) had mean (SD) weight losses of 7.4 (6.1) kg, with 25 (42%) remissions and 7 (12%) programme withdrawals. Those regaining >2 kg but not using RT (n = 39) had weight losses of 8.8 (6.0) kg, with 21 (54%) remissions and 4 (10%) programme withdrawals (all not significant). Twelve participants were never recorded as having regained >2 kg or using RTs and, at 2 years, their weight losses were 12.9 (9.2) kg, with 4 (33%) remissions and 8 (67%) programme withdrawals.

Conclusions: Most people with T2D experience weight regain >2 kg during the 2 years after substantial weight loss with a LED. Only one-third of RTs corrected their 2-kg regain, resulting in similar weight losses, remissions and programme withdrawals at 2 years compared to those not using RTs; however, both groups had weight losses below those not recorded as regaining >2 kg during WLM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jhn.12839DOI Listing
June 2021

Weight loss-induced increase in fasting ghrelin concentration is a predictor of weight regain: Evidence from the Diabetes Remission Clinical Trial (DiRECT).

Diabetes Obes Metab 2020 Dec 2. Epub 2020 Dec 2.

Human Nutrition, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.

Aim: To investigate whether appetite-related hormones were predictors of weight regain in the Diabetes Remission Clinical Trial (DiRECT).

Materials And Methods: DiRECT is a cluster-randomized clinical trial, designed to assess the effect of weight loss on type 2 diabetes remission. For this post hoc analysis, data were available for 253 (147 interventions, 106 controls) individuals with type 2 diabetes (age 53.6 ± 7.5 years, body mass index 34.7 ± 4.4 kg/m , 59% men). Intervention participants received a 24-month weight management programme, and controls remained on usual diabetes care. Fasting plasma concentrations of leptin, ghrelin, glucagon-like peptide-1 and peptide YY were measured at baseline, 12 months and 24 months in all participants, and at 5 months in a subset of participants in the intervention (n = 56) and control groups (n = 22). Potential predictors were examined using multivariable linear regression models.

Results: The intervention group lost 14.3 ± 6.0% body weight at 5 months but regained weight over time, with weight losses of 10.0 ± 7.5% at 12 months and 7.6 ± 6.3% at 24 months. Weight loss in controls was 1.1 ± 3.7% and 2.1 ± 5.0% at 12 and 24 months, respectively. Body weight increased by 2.3% (95% confidence interval [CI] 0.4, 4.1; P = 0.019) between 12 and 24 months for every 1-ng/mL increase in ghrelin between baseline and 12 months, and weight regain between 12 and 24 months was increased by 1.1% (95% CI 0.2, 2.0; P = 0.023) body weight for every 1-ng/mL increase in ghrelin at 12 months.

Conclusion: The rise in ghrelin (but not any other measured hormone) during diet-induced weight loss was a predictor of weight regain during follow-up, and concentrations remained elevated over time, suggesting a small but significant compensatory drive to regain weight. Attenuating the effects of ghrelin may improve weight-loss maintenance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.14274DOI Listing
December 2020

Weight loss induced increase in fasting ghrelin concentration is a predictor of weight regain: evidence from the Diabetes Remission Clinical Trial.

Diabetes Obes Metab 2020 Dec 2. Epub 2020 Dec 2.

Human Nutrition, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.

Aim: To investigate whether appetite-related hormones were predictors of weight regain in the Diabetes Remission Clinical Trial (DiRECT).

Materials And Methods: DiRECT is a cluster-randomised clinical trial designed to assess the effect of weight-loss on type 2 diabetes remission. For this post hoc analysis, data were available for 253 (147 interventions, 106 controls) individuals with type 2 diabetes (aged 53.6±7.5 years, BMI 34.7±4.4 kg/m, 59% males). Intervention participants received a 24-month weight-management programme and controls remained on usual diabetes care. Fasting plasma concentrations of leptin, ghrelin, GLP-1, and PYY were measured at baseline, 12 and 24-months in all participants, and at 5-months in a subset of interventions (n=56) and controls (n=22). Potential predictors were examined using multivariable linear regression models.

Results: The intervention group lost 14.3±6.0% body-weight at 5-months but regained over time, with weight-losses of 10.0±7.5% at 12-months and 7.6±6.3% at 24-months. Weight-loss in controls was 1.1±3.7% and 2.1±5.0% at 12 and 24-months, respectively. Body-weight increased by 2.3% [95% CI: 0.4,4.1]; p=0.019) between 12 and 24-months for every 1 ng/ml increase in ghrelin between baseline and 12-months, and weight regain between 12 and 24-months was increased by 1.1% (95% CI: 0.2,2.0; p=0.023) body-weight for every 1 ng/ml increase in ghrelin at 12-months.

Conclusion: The rise in ghrelin (but not any other measured hormone) during diet-induced weight-loss was a predictor of weight regain during follow-up, and concentrations remained elevated over time, suggesting a small but significant compensatory drive to regain weight. Attenuating the effects of ghrelin may improve WLM. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.14274DOI Listing
December 2020

Rationale and design of the British Heart Foundation (BHF) Coronary Microvascular Function and CT Coronary Angiogram (CorCTCA) study.

Am Heart J 2020 03 2;221:48-59. Epub 2019 Dec 2.

West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, UK; British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. Electronic address:

Microvascular and/or vasospastic anginas are relevant causes of ischemia with no obstructive coronary artery disease (INOCA) in patients after computed tomography coronary angiography (CTCA).

Objectives: Our research has 2 objectives. The first is to undertake a diagnostic study, and the second is to undertake a nested, clinical trial of stratified medicine.

Design: A prospective, multicenter, randomized, blinded, sham-controlled trial of stratified medicine (NCT03477890) will be performed. All-comers referred for clinically indicated CTCA for investigation of suspected coronary artery disease (CAD) will be screened in 3 regional centers. Following informed consent, eligible patients with angina symptoms are enrolled before CTCA and remain eligible if CTCA excludes obstructive CAD. Diagnostic study: Invasive coronary angiography involving an interventional diagnostic procedure (IDP) to assess for disease endotypes: (1) angina due to obstructive CAD (fractional flow reserve ≤0.80); (2) microvascular angina (coronary flow reserve <2.0 and/or index of microvascular resistance >25); (3) microvascular angina due to small vessel spasm (acetylcholine); (4) vasospastic angina due to epicardial coronary spasm (acetylcholine); and (5) noncoronary etiology (normal coronary function). The IDP involves direct invasive measurements using a diagnostic coronary guidewire followed by provocation testing with intracoronary acetylcholine. The primary outcome of the diagnostic study is the reclassification of the initial CTCA diagnosis based on the IDP. Stratified medicine trial: Participants are immediately randomized 1:1 in the catheter laboratory to therapy stratified by endotype (intervention group) or not (control group). The primary outcome of the trial is the mean within-subject change in Seattle Angina Questionnaire score at 6 months. Secondary outcomes include safety, feasibility, diagnostic utility (impact on diagnosis and certainty), and clinical utility (impact on treatment and investigations). Health status assessments include quality of life, illness perception, anxiety-depression score, treatment satisfaction, and physical activity. Participants who are not randomized will enter a follow-up registry. Health and economic outcomes in the longer term will be assessed using electronic patient record linkage.

Value: CorCTCA will prospectively characterize the prevalence of disease endotypes in INOCA and determine the clinical value of stratified medicine in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2019.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029345PMC
March 2020

Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism.

JAMA 2019 Nov;322(20):1977-1986

Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.

Importance: It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism.

Objective: To determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older.

Design, Setting, And Participants: Prospectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018.

Exposures: Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial).

Main Outcomes And Measures: Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9).

Results: Of 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 [95% CI, -2.7 to 5.2]; P = .53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, -0.1 [95% CI, -4.5 to 4.3]; P = .96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants).

Conclusions And Relevance: In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older.

Trial Registration: ClinicalTrials.gov Identifier: NCT01660126; Netherlands Trial Register: NTR3851.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2019.17274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822162PMC
November 2019

Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial.

Lancet Diabetes Endocrinol 2019 05 6;7(5):344-355. Epub 2019 Mar 6.

Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. Electronic address:

Background: The DiRECT trial assessed remission of type 2 diabetes during a primary care-led weight-management programme. At 1 year, 68 (46%) of 149 intervention participants were in remission and 36 (24%) had achieved at least 15 kg weight loss. The aim of this 2-year analysis is to assess the durability of the intervention effect.

Methods: DiRECT is an open-label, cluster-randomised, controlled trial done at primary care practices in the UK. Practices were randomly assigned (1:1) via a computer-generated list to provide an integrated structured weight-management programme (intervention) or best-practice care in accordance with guidelines (control), with stratification for study site (Tyneside or Scotland) and practice list size (>5700 or ≤5700 people). Allocation was concealed from the study statisticians; participants, carers, and study research assistants were aware of allocation. We recruited individuals aged 20-65 years, with less than 6 years' duration of type 2 diabetes, BMI 27-45 kg/m, and not receiving insulin between July 25, 2014, and Aug 5, 2016. The intervention consisted of withdrawal of antidiabetes and antihypertensive drugs, total diet replacement (825-853 kcal per day formula diet for 12-20 weeks), stepped food reintroduction (2-8 weeks), and then structured support for weight-loss maintenance. The coprimary outcomes, analysed hierarchically in the intention-to-treat population at 24 months, were weight loss of at least 15 kg, and remission of diabetes, defined as HbA less than 6·5% (48 mmol/mol) after withdrawal of antidiabetes drugs at baseline (remission was determined independently at 12 and 24 months). The trial is registered with the ISRCTN registry, number 03267836, and follow-up is ongoing.

Findings: The intention-to-treat population consisted of 149 participants per group. At 24 months, 17 (11%) intervention participants and three (2%) control participants had weight loss of at least 15 kg (adjusted odds ratio [aOR] 7·49, 95% CI 2·05 to 27·32; p=0·0023) and 53 (36%) intervention participants and five (3%) control participants had remission of diabetes (aOR 25·82, 8·25 to 80·84; p<0·0001). The adjusted mean difference between the control and intervention groups in change in bodyweight was -5·4 kg (95% CI -6·9 to -4·0; p<0·0001) and in HbA was -4·8 mmol/mol (-8·3 to -1·4 [-0·44% (-0·76 to -0·13)]; p=0·0063), despite only 51 (40%) of 129 patients in the intervention group using anti-diabetes medication compared with 120 (84%) of 143 in the control group. In a post-hoc analysis of the whole study population, of those participants who maintained at least 10 kg weight loss (45 of 272 with data), 29 (64%) achieved remission; 36 (24%) of 149 participants in the intervention group maintained at least 10 kg weight loss. Serious adverse events were similar to those reported at 12 months, but were fewer in the intervention group than in the control group in the second year of the study (nine vs 22).

Interpretation: The DiRECT programme sustained remissions at 24 months for more than a third of people with type 2 diabetes. Sustained remission was linked to the extent of sustained weight loss.

Funding: Diabetes UK.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-8587(19)30068-3DOI Listing
May 2019

ECG in suspected pulmonary embolism.

Postgrad Med J 2019 Jan 21;95(1119):12-17. Epub 2019 Jan 21.

Department of Medicine, Dumfries and Galloway Royal Infirmary, Dumfries, UK

Objective: To establish the diagnostic value of prespecified ECG changes in suspected pulmonary embolism (PE).

Methods: Retrospective case-control study in a district general hospital setting. We identified 189 consecutive patients with suspected PE whose CT pulmonary angiogram (CTPA) was positive for a first PE and for whom an ECG taken at the time of presentation was available. We matched these for age±3 years with 189 controls with suspected PE whose CTPA was negative. We considered those with large (n=76) and small (n=113) clot load separately. We scored each ECG for the presence or absence of eight features that have been reported to occur more commonly in PE.

Results: 20%-25% of patients with PE, including those with large clot load, had normal ECGs. The most common ECG abnormality in patients with PE was sinus tachycardia (28%). S1Q3T3 (3.7%), P pulmonale (0.5%) and right axis deviation (4.2%) were infrequent findings. Right bundle branch block (9.0%), atrial dysrhythmias (10.1%) and clockwise rotation (20.1%) occurred more frequently but were also common in controls. Right ventricular (RV) strain pattern was significantly more commonly in patients than controls, 11.1% vs 2.6% (sensitivity 11.1%, specificity 97.4%; OR 4.58, 95% CI 1.63 to 15.91; p=0.002), particularly in those with large clot load, 17.1% vs 2.6% (sensitivity 17.1%, specificity 97.4%; OR 7.55, 95% CI 1.62 to 71.58; p=0.005).

Conclusion: An ECG showing RV strain in a breathless patient is highly suggestive of PE. Many of the other ECG changes that have been described in PE occur too infrequently to be of predictive value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/postgradmedj-2018-136178DOI Listing
January 2019

Does progesterone prophylaxis to prevent preterm labour improve outcome? A randomised double-blind placebo-controlled trial (OPPTIMUM).

Health Technol Assess 2018 06;22(35):1-304

Centre for Healthcare Randomised Trials, Health Services Research Unit, University of Aberdeen, Aberdeen, UK.

Background: Progesterone prophylaxis is widely used to prevent preterm birth but is not licensed and there is little information on long-term outcome.

Objective: To determine the effect of progesterone prophylaxis in women at high risk of preterm birth on obstetric, neonatal and childhood outcomes.

Design: Double-blind, randomised placebo-controlled trial.

Setting: Obstetric units in the UK and Europe between February 2009 and April 2013.

Participants: Women with a singleton pregnancy who are at high risk of preterm birth because of either a positive fibronectin test or a negative fibronectin test, and either previous spontaneous birth at ≤ 34 weeks of gestation or a cervical length of ≤ 25 mm.

Interventions: Fibronectin test at 18 to 23 weeks of pregnancy to determine risk of preterm birth. Eligible women were allocated (using a web-based randomisation portal) to 200 mg of progesterone or placebo, taken vaginally daily from 22 to 24 until 34 weeks' gestation. Participants, caregivers and those assessing the outcomes were blinded to group assignment until data collection was complete.

Main Outcome Measures: There were three primary outcomes, as follows: (1) obstetric - fetal death or delivery before 34 weeks' gestation; (2) neonatal - a composite of death, brain injury on ultrasound scan (according to specific criteria in the protocol) and bronchopulmonary dysplasia; and (3) childhood - the Bayley-III cognitive composite score at 22-26 months of age.

Results: In total, 96 out of 600 (16%) women in the progesterone group and 108 out of 597 (18%) women in the placebo group had the primary obstetric outcome [odds ratio (OR) 0.86, 95% confidence interval (CI) 0.61 to 1.22]. Forty-six out of 589 (8%) babies of women in the progesterone group and 62 out of 587 (11%) babies of women in the placebo group experienced the primary neonatal outcome [OR 0.72, 95% CI 0.44 to 1.17]. The mean Bayley-III cognitive composite score of the children at 2 years of age was 97.3 points [standard deviation (SD) 17.9 points;  = 430] in the progesterone group and 97.7 points (SD 17.5 points;  = 439) in the placebo group (difference in means -0.48, 95% CI -2.77 to 1.81).

Limitations: Overall compliance with the intervention was 69%.

Harms: There were no major harms, although there was a trend of more deaths from trial entry to 2 years in the progesterone group (20/600) than in the placebo group (16/598) (OR 1.26, 95% CI 0.65 to 2.42).

Conclusions: In this study, progesterone had no significant beneficial or harmful effects on the primary obstetric, neonatal or childhood outcomes.The OPPTIMUM trial is now complete. We intend to participate in a comprehensive individual patient-level data meta-analysis examining women with a singleton pregnancy with a variety of risk factors for preterm birth.

Trial Registration: Current Controlled Trials ISRCTN14568373.

Funding: This trial was funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3310/hta22350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036405PMC
June 2018

Randomised, double-blind, placebo-controlled trials of non-individualised homeopathic treatment: systematic review and meta-analysis.

Syst Rev 2017 03 24;6(1):63. Epub 2017 Mar 24.

Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.

Background: A rigorous systematic review and meta-analysis focused on randomised controlled trials (RCTs) of non-individualised homeopathic treatment has not previously been reported. We tested the null hypothesis that the main outcome of treatment using a non-individualised (standardised) homeopathic medicine is indistinguishable from that of placebo. An additional aim was to quantify any condition-specific effects of non-individualised homeopathic treatment.

Methods: Literature search strategy, data extraction and statistical analysis all followed the methods described in a pre-published protocol. A trial comprised 'reliable evidence' if its risk of bias was low or it was unclear in one specified domain of assessment. 'Effect size' was reported as standardised mean difference (SMD), with arithmetic transformation for dichotomous data carried out as required; a negative SMD indicated an effect favouring homeopathy.

Results: Forty-eight different clinical conditions were represented in 75 eligible RCTs. Forty-nine trials were classed as 'high risk of bias' and 23 as 'uncertain risk of bias'; the remaining three, clinically heterogeneous, trials displayed sufficiently low risk of bias to be designated reliable evidence. Fifty-four trials had extractable data: pooled SMD was -0.33 (95% confidence interval (CI) -0.44, -0.21), which was attenuated to -0.16 (95% CI -0.31, -0.02) after adjustment for publication bias. The three trials with reliable evidence yielded a non-significant pooled SMD: -0.18 (95% CI -0.46, 0.09). There was no single clinical condition for which meta-analysis included reliable evidence.

Conclusions: The quality of the body of evidence is low. A meta-analysis of all extractable data leads to rejection of our null hypothesis, but analysis of a small sub-group of reliable evidence does not support that rejection. Reliable evidence is lacking in condition-specific meta-analyses, precluding relevant conclusions. Better designed and more rigorous RCTs are needed in order to develop an evidence base that can decisively provide reliable effect estimates of non-individualised homeopathic treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13643-017-0445-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366148PMC
March 2017

Age-adjusted D-dimer excludes pulmonary embolism and reduces unnecessary radiation exposure in older adults: retrospective study.

Postgrad Med J 2017 Jul 9;93(1101):420-424. Epub 2016 Dec 9.

Medical Unit, Dumfries and Galloway Royal Infirmary, Dumfries, UK.

Background: Patients in whom a diagnosis of pulmonary embolism (PE) is suspected and whose D-dimers are elevated frequently require CT pulmonary angiogram (CTPA) for diagnosis. Because D-dimer rises with age, an age-adjusted D-dimer threshold may prevent unnecessary radiation exposure from CTPA in older patients.

Objective: To determine the efficacy and safety of implementing an age-adjusted D-dimer threshold to exclude PE.

Design, Settings And Patients: Retrospective comparison of conventional and age-adjusted D-dimer thresholds in 1000 consecutive patients who had both D-dimer and CTPA.

Main Outcome Measures: Conventional and age-adjusted D-dimer thresholds for excluding PE were <250 ng/mL and 5× age for patients older than 50 years, respectively. We defined patients as unlikely to have PE using the revised Geneva score (RGS) and two different categories of clinical risk: RGS ≤5 and RGS ≤10.

Results: We diagnosed PE by CTPA in 244 (24.4%) patients. 3/86 patients (3.5%) whose D-dimer was below the conventional threshold of 250 ng/mL had PE (RGS 3, 9 and 14), all of which were judged to be light clot load (group 1). 3/108 patients (2.8%) whose D-dimer lay between 250 ng/mL and the age-adjusted threshold had PE (RGS 6, 8 and 9), all of which were again judged to be light clot load (group 2). 62/108 group 2 patients with RGS ≤5 were considered unlikely to have PE as were 102/108 using the RGS clinical risk category ≤10. None of the 62 patients with RGS ≤5 had PE while 3/102 patients with RGS ≤10 had PE. 236/806 patients (29.3%) whose D-dimer was above the age-adjusted threshold had PE (group 3).

Conclusions: In a consecutive series of 1000 patients, an RGS ≤5 and an age-adjusted D-dimer would have led to 62 fewer CTPA at a cost of no missed PEs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/postgradmedj-2016-134552DOI Listing
July 2017

Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial.

J Neurol Neurosurg Psychiatry 2017 Jan 18;88(1):38-44. Epub 2016 Oct 18.

Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.

Objective: The Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial was a multicentre, randomised, controlled clinical trial comparing intravenous thrombolysis (IVT) alone with IVT and adjunctive intra-arterial mechanical thrombectomy (MT) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography (CTA).

Design: Eligible patients had IVT started within 4.5 hours of stroke symptom onset. Those randomised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device, with target interval times for IVT start to arterial puncture of <90 min. The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale (mRS) score of 0-2 at day 90.

Results: Ten UK centres enrolled 65 patients between April 2013 and April 2015. Median National Institutes of Health Stroke Scale score was 16 (IQR 13-21). Median stroke onset to IVT start was 120 min. In the intention-to-treat analysis, there was no significant difference in disability-free survival at day 90 with MT (absolute difference 11%, adjusted OR 2.12, 95% CI 0.65 to 6.94, p=0.20). Secondary analyses showed significantly greater likelihood of full neurological recovery (mRS 0-1) at day 90 (OR 7.6, 95% CI 1.6 to 37.2, p=0.010). In the per-protocol population (n=58), the primary and most secondary clinical outcomes significantly favoured MT (absolute difference in mRS 0-2 of 22% and adjusted OR 4.9, 95% CI 1.2 to 19.7, p=0.021).

Conclusions: The trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability-free survival.

Trial Registration Number: NCT01745692; Results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2016-314117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256149PMC
January 2017

Excessive Age-Related Decline in Functional Ovarian Reserve in Infertile Women: Prospective Cohort of 15,500 Women.

J Clin Endocrinol Metab 2016 09 6;101(9):3548-54. Epub 2016 Jul 6.

Department of Obstetrics and Gynaecology (S.I., S.M.N.), School of Medicine, University of Glasgow, Glasgow G31 2ER, United Kingdom; IVI Clinic (C.I.S., M.C., J.G.V.), 28023 Madrid, Spain; Robertson Centre for Biostatistics (C.-M.M.), University of Glasgow, Glasgow G12 8QQ, United Kingdom.

Context: Whether infertile women exhibit accelerated ovarian aging and whether a low ovarian reserve is overrepresented in infertility populations is not known.

Objective: To compare the age-related decline in antral follicle count (AFC), a biomarker of the ovarian reserve, in fertile and infertile women.

Design: Cross-sectional data from a large prospective cohort study conducted from January 2013 to December 2014.

Setting: Thirteen fertility centers across Spain.

Patients Or Other Participants: Consecutive women aged 18 to 45 years of age attending the fertility centers either seeking fertility treatment or as fertile women wishing to act as potential oocyte donors.

Intervention(s): Standardized AFC assessment on day 2 to 4 of the cycle.

Main Outcome Measure(s): Age-related decline of AFC for both fertile and infertile women.

Results: A total of 15 500 women, of whom 5722 were potential donors and 9778 were patients seeking fertility treatment, participated in the study. Average AFC was greater in potential oocyte donors than in infertile women (20 [interquartile range, 16-24] vs 10 [interquartile range, 6-15], respectively; P < .001), a difference that was maintained after adjustment for age (P < .001) in a model predicting log(AFC) from donor vs infertility, adjusting for 2-year age bands. The age-related decline in AFC was much steeper in infertile women compared with that of potential oocyte donors, with an increased prevalence of a low ovarian reserve (AFC < 5) at all ages in infertile women.

Conclusions: The age-related decline in AFC was substantially greater in infertility patients than potential oocyte donors. Overrepresentation in infertility populations of women with low ovarian reserve may be an additional functional cause of infertility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2015-4279DOI Listing
September 2016

Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial.

Lancet 2016 05 24;387(10033):2106-2116. Epub 2016 Feb 24.

Centre for Healthcare Randomised Trials, Health Services Research Unit, University of Aberdeen, Aberdeen, UK.

Background: Progesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on the child.

Methods: We did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22-24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at ≤34 weeks and 0 days of gestation, or a cervical length ≤25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth [any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears]). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primary outcomes: fetal death or birth before 34 weeks and 0 days gestation (obstetric), a composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and a standardised cognitive score at 2 years of age (childhood), imputing values for deaths. Randomisation was done through a web portal, with participants, investigators, and others involved in giving the intervention, assessing outcomes, or analysing data masked to treatment allocation until the end of the study. Analysis was by intention to treat. This trial is registered at ISRCTN.com, number ISRCTN14568373.

Findings: Between Feb 2, 2009, and April 12, 2013, we randomly assigned 1228 women to the placebo group (n=610) and the progesterone group (n=618). In the placebo group, data from 597, 587, and 439 women or babies were available for analysis of obstetric, neonatal, and childhood outcomes, respectively; in the progesterone group the corresponding numbers were 600, 589, and 430. After correction for multiple outcomes, progesterone had no significant effect on the primary obstetric outcome (odds ratio adjusted for multiple comparisons [OR] 0·86, 95% CI 0·61-1·22) or neonatal outcome (OR 0·62, 0·38-1·03), nor on the childhood outcome (cognitive score, progesterone group vs placebo group, 97·3 [SD 17·9] vs 97·7 [17·5]; difference in means -0·48, 95% CI -2·77 to 1·81). Maternal or child serious adverse events were reported in 70 (11%) of 610 patients in the placebo group and 59 (10%) of 616 patients in the progesterone group (p=0·27).

Interpretation: Vaginal progesterone was not associated with reduced risk of preterm birth or composite neonatal adverse outcomes, and had no long-term benefit or harm on outcomes in children at 2 years of age.

Funding: Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. The EME Programme is funded by the MRC and NIHR, with contributions from the Chief Scientist Office in Scotland and National Institute for Social Care and Research in Wales.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(16)00350-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406617PMC
May 2016

Counselling versus low-intensity cognitive behavioural therapy for persistent sub-threshold and mild depression (CLICD): a pilot/feasibility randomised controlled trial.

BMC Psychiatry 2015 Aug 15;15:197. Epub 2015 Aug 15.

General Practice and Primary Care, Institute of Health and Wellbeing, University of Glasgow, 1 Horselethill Road, Glasgow, G12 9LX, UK.

Background: Persistent depressive symptoms below the threshold criteria for major depression represent a chronic condition with high risk of progression to a diagnosis of major depression. The evidence base for psychological treatments such as Person-Centred Counselling and Low-Intensity Cognitive Behavioural Therapy for sub-threshold depressive symptoms and mild depression is limited, particularly for longer-term outcomes.

Methods: This study aimed to test the feasibility of delivering a randomised controlled trial into the clinical and cost effectiveness of Low-Intensity Cognitive Behavioural Therapy versus Person-Centred Counselling for patients with persistent sub-threshold depressive symptoms and mild depression. The primary outcome measures for this pilot/feasibility trial were recruitment, adherence and retention rates at six months from baseline. An important secondary outcome measure was recovery from, or prevention of, depression at six months assessed via a structured clinical interview by an independent assessor blind to the participant's treatment condition. Thirty-six patients were recruited in five general practices and were randomised to either eight weekly sessions of person-centred counselling each lasting up to an hour, or up to eight weeks of cognitive-behavioural self-help resources with guided telephone support sessions lasting 20-30 minutes each.

Results: Recruitment rate in relation to the number of patients approached at the general practices was 1.8 %. Patients attended an average of 5.5 sessions in both interventions. Retention rate for the 6-month follow-up assessments was 72.2 %. Of participants assessed at six months, 71.4 % of participants with a diagnosis of mild depression at baseline had recovered, while 66.7 % with a diagnosis of persistent subthreshold depression at baseline had not developed major depression. There were no significant differences between treatment groups for both recovery and prevention of depression at six months or on any of the outcome measures.

Conclusions: It is feasible to recruit participants and successfully deliver both interventions in a primary care setting to patients with subthreshold and mild depression; however recruiting requires significant input at the general practices. The evidence from this study suggests that short-term Person-Centred Counselling and Low-Intensity Cognitive Behaviour Therapy are potentially effective and their effectiveness should be evaluated in a larger randomised controlled study which includes a health economic evaluation.

Trial Registration: Current Controlled Trials ISRCTN60972025 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12888-015-0582-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536887PMC
August 2015

Poor symptom control is associated with reduced CT scan segmental airway lumen area in smokers with asthma.

Chest 2015 Mar;147(3):735-744

Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow.

Background: Cigarette smoking is associated with worse symptoms in asthma and abnormal segmental airways in healthy subjects. We tested the hypothesis that current symptom control in smokers with asthma is associated with altered segmental airway dimensions measured by CT scan.

Methods: In 93 subjects with mild, moderate, and severe asthma (smokers and never smokers), we recorded Asthma Control Questionnaire-6 (ACQ-6) score, spirometry (FEV1; forced expiratory flow rate, midexpiratory phase [FEF(25%-75%)]), residual volume (RV), total lung capacity (TLC), and CT scan measures of the right bronchial (RB) and left bronchial (LB) segmental airway dimensions (wall thickness, mm; lumen area, mm²) in the RB3/LB3, RB6/LB6, and RB10/LB10 (smaller) airways.

Results: The CT scan segmental airway (RB10 and LB10) lumen area was reduced in smokers with asthma compared with never smokers with asthma; RB10, 16.6 mm² (interquartile range, 12.4-19.2 mm²) vs 19.6 mm² (14.7-24.2 mm²) (P = .01); LB10, 14.8 mm² (12.1-19.0 mm²) vs 19.9 mm² (14.5-25.0 mm²) (P = .003), particularly in severe disease, with no differences in wall thickness or in larger airway (RB3 and LB3) dimensions. In smokers with asthma, a reduced lumen area in fifth-generation airways (RB10 or LB10) was associated with poor symptom control (higher ACQ-6 score) (-0.463 [-0.666 to -0.196], P = .001, and -0.401 [-0.619 to -0.126], P = .007, respectively) and reduced postbronchodilator FEF(25%-75%) (0.521 [0.292-0.694], P < .001, and [0.471 [0.236-0.654], P = .001, respectively) and higher RV/TLC %.

Conclusions: The CT scan segmental airway lumen area is reduced in smokers with asthma compared with never smokers with asthma, particularly in severe disease, and is associated with worse current symptom control and small airway dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1378/chest.14-1119DOI Listing
March 2015

Reference range for the antimüllerian hormone Generation II assay: a population study of 10,984 women, with comparison to the established Diagnostics Systems Laboratory nomogram.

Fertil Steril 2014 Feb 9;101(2):523-9. Epub 2013 Nov 9.

Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.

Objective: To develop an optimal model and age-specific centiles for the decline in antimüllerian hormone (AMH) as measured by the new Beckman Coulter AMH Generation II (Gen II) assay and compare this to the previous nomogram derived for the Diagnostics Systems Laboratory (DSL) assay.

Design: Multicenter retrospective population study, with validation of linear, biphasic linear, differential, power, and quadratic equations.

Setting: Two clinical pathology laboratories.

Patient(s): A new cohort of 10,984 women aged 25 to 45 years old attending infertility clinics, randomly divided into a training cohort of 5,492 women and a validation cohort of 5,492 women, and an existing cohort of 9,601 women, who had contributed to the development and validation of a nomogram for AMH measured by the DSL assay.

Intervention(s): Serum measurement of AMH as determined by the Beckman Coulter AMH Generation II assay in 10,984 women.

Main Outcome Measure(s): Optimal model for the decline in AMH as measured by the AMH Gen II assay with age, with age-specific 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles.

Result(s): A quadratic model defined as (2.431 + 0.089 * Age + -0.003 * Age(2)) fitted the decline in AMH with age. The anticipated 40% increase in age-specific population values relative to the previously validated DSL assay nomogram was not observed.

Conclusion(s): Age-specific reference ranges for the AMH gen II assay suggest a systematic shift in assay calibration since initial evaluation and commercial release of the AMH Gen II assay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2013.10.021DOI Listing
February 2014

Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial.

JAMA Intern Med 2013 Oct;173(18):1672-9

Importance: Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension. No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension, the most common pattern of hypertension in older people.

Objective: To test whether high-dose, intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension.

Design: Parallel group, double-blind, placebo-controlled randomized trial.

Setting: Primary care clinics and hospital clinics.

Participants: Patients 70 years and older with isolated systolic hypertension (supine systolic blood pressure >140 mm Hg and supine diastolic blood pressure <90 mm Hg) and baseline 25-hydroxyvitamin D levels less than 30 ng/mL were randomized into the trial from June 1, 2009, through May 31, 2011.

Interventions: A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year.

Main Outcomes And Measures: Difference in office blood pressure, 24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, insulin resistance, and b-type natriuretic peptide level during 12 months.

Results: A total of 159 participants were randomized (mean age, 77 years). Mean baseline office systolic blood pressure was 163/78 mm Hg. Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group (+8 ng/mL at 1 year, P < .001). No significant treatment effect was seen for mean (95% CI) office blood pressure (−1 [−6 to 4]/−2 [−4 to 1] mm Hg at 3 months and 1 [−2 to 4]/0 [−2 to 2] mm Hg overall treatment effect). No significant treatment effect was evident for any of the secondary outcomes (24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, glucose level, and walking distance). There was no excess of adverse events in the treatment group, and the total number of falls was nonsignificantly lower in the group receiving vitamin D (36 vs 46, P = .24).

Conclusions And Relevance: Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension.

Trial Registration: isrctn.org Identifier: ISRCTN92186858.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamainternmed.2013.9043DOI Listing
October 2013

Searching for gene expression differences in primary fibroblasts between patients with one and two neoplasms in childhood.

Pediatr Hematol Oncol 2013 Feb 9;30(1):33-45. Epub 2012 Nov 9.

Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Genetic factors are important for developing primary and subsequent malignancies in children. This study investigated the role of genetic factors involved in DNA-repair. Designed as a feasibility study, it addressed the possibility of obtaining samples for genetic analyses from former patients through the German Childhood Cancer Registry. Testing feasibility was as important as the biological question itself. We analyzed the expression of DNA-repair genes in untreated primary fibroblasts of 20 individuals with a second neoplasm compared to 20 matched single neoplasm cases using customized cDNA microarrays (1344 gene sequences, about 800 genes). Matching was by first neoplasm, age, and year of first diagnosis. Forty-six percent of the 52 contacted second neoplasm cases and 18% of the 132 single neoplasm patients participated in the study. The DNA-repair gene results show small differences in the basal gene expression of FTH1 and CDKN1A. To our knowledge, this is the first study using gene expression arrays in untreated primary fibroblasts regarding second neoplasms after a childhood neoplasm. We were able to recruit childhood cancer patients for genetic analyses long after diagnosis. The biological importance of the differences in the DNA-repair gene expression has to be elucidated yet.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/08880018.2012.735747DOI Listing
February 2013

Feasibility of screening for and treating vitamin D deficiency in forensic psychiatric inpatients.

J Forensic Leg Med 2012 Nov 4;19(8):457-64. Epub 2012 May 4.

NHS Scotland State Hospital and NHS Education for Scotland, 2 Central Quay, Glasgow G3 8BW, United Kingdom.

Neuroleptic and anti-epileptic medication, inadequate vitamin D intake and limited solar exposure increase the risk of vitamin D deficiency in high security psychiatric environments. Of the 33 inpatients (40% selected; 21% of hospital population) completing this cross-sectional study, 36% had insufficient and 58% deficient vitamin D. Five patients with vitamin D deficiency had secondary hyperparathyroidism, two of whom had osteopenia on dual-emission X-ray absorptiometry. At 1-year follow up, of the 31 patients eligible, 15 had accepted and continued supplements. Systematic screening is therefore necessary due to mental health and consent issues. Implications of supplementation and grounds access are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jflm.2012.04.003DOI Listing
November 2012

Interaction of personality traits with social deprivation in determining mental wellbeing and health behaviours.

J Public Health (Oxf) 2012 Dec 2;34(4):615-24. Epub 2012 May 2.

Glasgow Clinical Research Facility, 1st Floor, Tennent Building, 38 Church Street, Western Infirmary, Glasgow G11 6NT, UK.

Background: Associations between personality traits, mental wellbeing and good health behaviours were examined to understand further the social and psychological context of the health divide.

Methods: In a cross-sectional study, 666 subjects recruited from areas of high and low socioeconomic deprivation had personality traits and mental wellbeing assessed, and lifestyle behaviours quantified. Regression models (using deprivation as a moderating variable) assessed the extent to which personality traits and mental wellbeing predicted health behaviour.

Results: Deprived (vs. affluent) subjects exhibited similar levels of extraversion but higher levels of neuroticism and psychoticism, more hopelessness, less sense of coherence, lower self-esteem and lower self-efficacy (all P< 0.001). They ate less fruit and vegetables, smoked more and took less aerobic exercise (all P< 0.001). In the deprived group, personality traits were significantly more important predictors of mental wellbeing than in the least deprived group (P< 0.01 for interaction), and mental wellbeing and extraversion appeared more strongly related to good health behaviours.

Conclusions: Persistence of a social divide in health may be related to interactions between personality, mental wellbeing and the adoption of good health behaviours in deprived areas. Effectiveness of health messages may be enhanced by accommodating the variation in the levels of extraversion, neuroticism, hopelessness and sense of coherence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/pubmed/fds030DOI Listing
December 2012

The Heart failure and Optimal Outcomes from Pharmacy Study (HOOPS): rationale, design, and baseline characteristics.

Eur J Heart Fail 2011 Aug;13(8):917-24

NHS Greater Glasgow and Clyde, Glasgow, Scotland, UK.

Aims: The effect on mortality and morbidity of pharmacist-led intervention to optimize pharmacological therapy in patients with systolic heart failure (HF) has not been tested in a large-scale, long-term, clinical trial.

Methods: We describe the rationale and design of a UK, primary care-based, prospective cluster-randomized controlled trial of a pharmacist-led intervention in HF and report baseline characteristics of the patients randomized. Eighty-seven practices (1092 patients) were assigned to the intervention arm and 87 practices (1077 patients) to usual care. The average age of patients at baseline was 71 years, 70% were male, 86% were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and 62% with a beta-blocker. Data for the primary outcome of death from any cause or hospitalization for HF will be available up to 31 December 2010, giving a mean follow-up of 5 years. More than 750 patients would have experienced the primary outcome during this period. The first secondary outcome is death from any cause or hospitalization for a cardiovascular reason. Deaths and hospitalizations are being identified using the Scottish National Health Service electronic patient record-linkage system (hence the delay between the end of follow-up and database lock).

Conclusion: This trial is powered to provide a robust evaluation of the effect of pharmacist-led treatment optimization in patients with systolic HF in primary care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurjhf/hfr083DOI Listing
August 2011

First-trimester circulating 25-hydroxyvitamin D levels and development of gestational diabetes mellitus.

Diabetes Care 2011 May 31;34(5):1091-3. Epub 2011 Mar 31.

Department of Maternal Fetal Medicine, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, UK.

Objective: To investigate the association between first-trimester maternal serum levels of 25-hydroxyvitamin D (25-OH-D) as measured by liquid chromatography-tandem mass spectrometry and development of gestational diabetes mellitus (GDM).

Research Design And Methods: We conducted a case-control study involving 248 women in the first-trimester of pregnancy, 90 of whom developed GDM and 158 remained normoglycemic.

Results: Although booking 25-OH-D levels correlated negatively with 2-h glucose post-oral glucose tolerance test and positively with HDL cholesterol, as well as with ethnicity, obesity, and smoking (all P < 0.05), there were no statistically significant differences in baseline maternal mean 25-OH-D levels between those who subsequently developed GDM, 18.9 ng/mL (SD 10.7) and those who remained normoglycemic, 19.0 ng/mL (10.7) (P = 0.874), even after adjustment for possible confounders including sampling month (P = 0.784).

Conclusions: Our large and well-phenotyped prospective study did not find evidence of an association between first-trimester maternal levels of 25-OH-D and subsequent development of GDM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc10-2264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114479PMC
May 2011

First-trimester prediction of gestational diabetes mellitus: examining the potential of combining maternal characteristics and laboratory measures.

Diabetes 2010 Dec 28;59(12):3017-22. Epub 2010 Sep 28.

Department of Maternal Fetal Medicine, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, UK.

Objective: Predictors of gestational diabetes mellitus (GDM) have been widely studied, but few studies have considered multiple measures. Our objective was to integrate several potential GDM predictors with consideration to both simple and novel measures and to determine the extent to which GDM can be predicted in the first trimester.

Research Design And Methods: We identified first-trimester maternal samples from 124 women who developed GDM and 248 control subjects who did not. We gathered data on age, BMI, parity, race, smoking, prior GDM, family history of diabetes, and blood pressure. Using retrieved samples, we measured routine (lipids, high-sensitivity C-reactive protein, and γ-glutamyltransferase) and novel (adiponectin, E-selectin, and tissue plasminogen activator [t-PA]) parameters. We determined independent predictors from stepwise regression analyses, calculated areas under the receiver-operating characteristic curves (AUC-ROC), and integrated discrimination improvement (IDI) for relevant models.

Results: Compared with control subjects, women who subsequently developed GDM were older, had higher BMIs, were more likely to be of Asian origin, had a history of GDM or family history of type 2 diabetes, and had higher systolic blood pressure (P < 0.05 for all). With regard biochemical measures, stepwise analyses identified only elevated t-PA and low HDL cholesterol levels as significant (P ≤ 0.015) independent predictors of GDM beyond simple non-laboratory-based maternal measures. Their inclusion improved the AUC-ROC from 0.824 to 0.861 and IDI by 0.052 (0.017-0.115).

Conclusions: GDM can be usefully estimated from a mix of simple questions with potential for further improvement by specific blood measures (lipids and t-PA).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/db10-0688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992761PMC
December 2010

Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma in consideration of concomitant stage of liver cirrhosis.

J Clin Gastroenterol 2009 May-Jun;43(5):489-95

I Department of Internal Medicine, Johannes Gutenberg-University Mainz, Germany.

Goals And Background: The multikinase inhibitor sorafenib provides survival benefit for patients with advanced hepatocellular carcinoma (HCC) and liver cirrhosis (LCI) Child-Pugh A. We report our experiences with sorafenib in advanced HCC, particularly in patients with LCI Child-Pugh B/C, where only limited data are available in regard to safety and efficacy of sorafenib.

Methods: Thirty-four patients with advanced HCC were treated with sorafenib regardless of liver function and prior anticancer therapy. Adverse events (AEs) were graded using Common Toxicity Criteria version 3.0, tumor response was assessed according to Response Evaluation Criteria in Solid Tumors.

Results: Fifteen patients presented without LCI or with LCI Child- Pugh A, 15/4 patients had LCI Child-Pugh B/C. Barcelona Clinic Liver Cancer stage was B/C/D in 4/22/8 patients. During treatment period (median 2.2 mo), therapy was discontinued in 61.8% of patients due to tumor progression (32.3%), death (17.6%), AEs (8.8%), or noncompliance (2.9%). Most common grade 3/4 AEs included liver dysfunction (23.5%), diarrhea (14.7%), increased lipase (8.8%), fatigue (8.8%), and hand-foot skin reaction (5.9%). Worsening liver dysfunction/failure was more frequent (P=0.036) in patients with LCI Child-Pugh B/C compared with patients with maintained liver function (no LCI/LCI Child-Pugh A). Median overall survival was 7.2 months for patients with maintained liver function versus 3.3/3.4 months for patients with LCI Child-Pugh B/C.

Conclusions: These data do not support the use of sorafenib in patients with LCI Child-Pugh C, and patients with LCI Child-Pugh B should be treated with caution until larger trials provide more safety data and a clinically relevant survival benefit under sorafenib therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0b013e31818ddfc6DOI Listing
September 2009

Cystatin C and cardiovascular mortality in patients with coronary artery disease and normal or mildly reduced kidney function: results from the AtheroGene study.

Eur Heart J 2009 Feb 19;30(3):314-20. Epub 2009 Jan 19.

Department of Medicine II, Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.

Aims: Chronic kidney disease is associated with increased risk of cardiovascular disease. Cystatin C is a promising marker to reliably mirror renal function. The role of cystatin C in patients with coronary artery disease (CAD) and normal or mildly reduced kidney function is the subject of current investigation.

Methods And Results: In 2162 patients, over the whole spectrum of CAD, baseline cystatin C concentrations were measured. Patients with an estimated glomerular filtration rate of < or =60 mL/min per 1.73 m(2) (n = 295) were excluded. In patients with complete follow-up information (n = 1827), 66 cardiovascular deaths were registered during a median follow-up of 3.65 years. Logarithmically transformed, standardized cystatin C was associated with cardiovascular death [hazard ratio: 1.94, 95% confidence interval (CI): 1.59-2.37, P < 0.001]. A potential threshold effect was observed; patients in the upper quartile had a 3.87-fold (95% CI: 2.33-6.42; P < 0.001) risk of mortality compared with the pooled lower quartiles. This risk association remained robust after adjustment for potential confounders including classical risk factors and N-terminal pro B-type natriuretic peptide. Serum creatinine was not associated with the outcome in this group of patients with normal renal function.

Conclusion: Results of this prospective study show that cystatin C is a potent predictor of cardiovascular mortality beyond classical risk factors in patients with CAD and normal or mildly reduced kidney function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehn598DOI Listing
February 2009
-->