Tag: pubmed

Trials. 2022 Jul 27;23(1):606. doi: 10.1186/s13063-022-06429-z.

ABSTRACT

BACKGROUND: Carotid endarterectomy is currently recommended for patients with recently symptomatic carotid stenosis ≥50%, based on randomised trials conducted 30 years ago. Several factors such as carotid plaque ulceration, age and associated comorbidities might influence the risk-benefit ratio of carotid revascularisation. A model developed in previous trials that calculates the future risk of stroke based on these features can be used to stratify patients into low, intermediate or high risk. Since the original trials, medical treatment has improved significantly. Our hypothesis is that patients with carotid stenosis ≥50% associated with a low to intermediate risk of stroke will not benefit from additional carotid revascularisation when treated with optimised medical therapy. We also hypothesise that prediction of future risk of stroke in individual patients with carotid stenosis can be improved using the results of magnetic resonance imaging (MRI) of the carotid plaque.

METHODS: Patients are randomised between immediate revascularisation plus OMT versus OMT alone. Suitable patients are those with asymptomatic or symptomatic carotid stenosis ≥50% with an estimated 5-year risk of stroke of <20%, as calculated using the Carotid Artery Risk score. MRI of the brain at baseline and during follow-up will be used as a blinded measure to assess the incidence of silent infarction and haemorrhage, while carotid plaque MRI at baseline will be used to investigate the hypotheses that plaque characteristics determine future stroke risk and help identify a subgroup of patients that will benefit from revascularisation. An initial analysis will be conducted after recruitment of 320 patients with baseline MRI and a minimum of 2 years of follow-up, to provide data to inform the design and sample size for a continuation or re-launch of the study. The primary outcome measure of this initial analysis is the combined 2-year rate of any clinically manifest stroke, new cerebral infarct on MRI, myocardial infarction or periprocedural death.

DISCUSSION: ECST-2 will provide new data on the efficacy of modern optimal medical therapy alone versus added carotid revascularisation in patients with carotid stenosis at low to intermediate risk of future stroke selected by individualised risk assessment. We anticipate that the results of baseline brain and carotid plaque MRI will provide data to improve the prediction of the risk of stroke and the effect of treatment in patients with carotid stenosis.

TRIAL REGISTRATION: ISRCTN registry ISRCTN97744893 . Registered on 05 July 2012.

PMID:35897114 | DOI:10.1186/s13063-022-06429-z

Pilot Feasibility Stud. 2022 Jul 27;8(1):155. doi: 10.1186/s40814-022-01095-z.

ABSTRACT

BACKGROUND: Staff absenteeism and presenteeism incur high costs to the NHS and are associated with adverse health outcomes. The main causes are musculoskeletal complaints and mental ill-health, which are potentially modifiable, and cardiovascular risk factors are also common. We will test the feasibility of an RCT to evaluate the clinical and cost-effectiveness of an employee health screening clinic on reducing sickness absenteeism and presenteeism.

METHODS: This is an individually randomised controlled pilot trial aiming to recruit 480 participants. All previously unscreened employees from four hospitals within three UK NHS hospital Trusts will be eligible. Those randomised to the intervention arm will be invited to attend an employee health screening clinic consisting of a screening assessment for musculoskeletal (STarT MSK and STarT Back), mental (PHQ-9 and GAD-7) and cardiovascular (NHS Health Check if aged ≥ 40, lifestyle check if < 40 years) health. Screen positives will be given advice and/or referral to recommended services. Those randomised to the control arm will receive usual care. Participants will complete a questionnaire at baseline and 26 weeks; anonymised absenteeism and staff demographics will also be collected from personnel records. The co-primary outcomes are as follows: recruitment, referrals and uptake of recommended services in the intervention arm. Secondary outcomes include the following: results of screening assessments, uptake of individual referrals, reported changes in health behaviours, acceptability and feasibility of intervention, indication of contamination and costs. Outcomes related to the definitive trial include self-reported and employee records of absenteeism with reasons. Process evaluation to inform a future trial includes interviews with participants, intervention delivery staff and service providers receiving referrals. Analyses will include presentation of descriptive statistics, framework analysis for qualitative data and costs and consequences presented for health economics.

DISCUSSION: The study will provide data to inform the design of a definitive RCT which aims to find an effective and cost-effective method of reducing absenteeism and presenteeism amongst NHS staff. The feasibility study will test trial procedures, and process outcomes, including the success of strategies for including underserved groups, and provide information and data to help inform the design and sample size for a definitive trial.

TRIAL REGISTRATION: ISRCTN reference number 10237475 .

PMID:35897113 | DOI:10.1186/s40814-022-01095-z

Trials. 2022 Jul 27;23(1):601. doi: 10.1186/s13063-022-06516-1.

ABSTRACT

BACKGROUND: To assess the quality of reporting of RCT protocols approved by UK research ethics committees before and after the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline.

METHODS: We had access to RCT study protocols that received ethical approval in the UK in 2012 (n=103) and 2016 (n=108). From those, we assessed the adherence to the 33 SPIRIT items (i.e. a total of 64 components of the 33 SPIRIT items). We descriptively analysed the adherence to SPIRIT guidelines as proportion of adequately reported items (median and interquartile range [IQR]) and stratified the results by year of approval and sponsor.

RESULTS: The proportion of reported SPIRIT items increased from a median of 64.9% (IQR, 57.6-69.2%) in 2012 to a median of 72.5% (IQR, 65.3-78.3%) in 2016. Industry-sponsored RCTs reported more SPIRIT items in 2012 (median 67.4%; IQR, 64.1-69.4%) compared to non-industry-sponsored trials (median 59.8%; IQR, 46.5-67.7%). This gap between industry- and non-industry-sponsored trials increased in 2016 (industry-sponsored: median 75.6%; IQR, 71.2-79.0% vs non-industry-sponsored: median 65.3%; IQR, 51.6-76.3%).

CONCLUSIONS: The adherence to SPIRIT guidelines has improved in the UK from 2012 to 2016 but remains on a modest level, especially for non-industry-sponsored RCTs.

PMID:35897110 | DOI:10.1186/s13063-022-06516-1

BMC Ophthalmol. 2022 Jul 27;22(1):323. doi: 10.1186/s12886-022-02548-y.

ABSTRACT

PURPOSE: To compare the visual outcomes of digital and slit-beam manual marking for toric intraocular lenses (IOL) in cataract surgery.

SETTING: Single-center, Beijing Tongren Hospital, China.

DESIGN: Retrospective study.

METHODS: All patients with cataracts and regular corneal astigmatism greater than 0.75 diopters (D) underwent cataract surgery and astigmatism correction between June 2019 and June 2020. To mark the target axis of the toric IOL and the location of the incision, intraoperative digital marking was used by Callisto eye image-guided system in one group, while preoperative manual slit-beam marking was used in the other group. Uncorrected and best-corrected spectacle visual acuity, refraction, toric IOL axis, total higher order aberrations, coma, spherical aberration, and trefoil were evaluated at 1, 4, and 12 weeks postoperatively.

RESULTS: Seventy-two eyes of 58 patients were included. At 3 months after surgery, the mean residual refractive cylinder was 0.42 ± 0.45D in the digital group and 0.39 ± 0.40D in the manual group (P = 0.844). There were no significant differences between groups in spherical equivalent refraction, uncorrected and best-corrected spectacle visual acuity, or the parameters of vector analysis. All toric IOL alignment errors were within 10° of the intended axis, and among them, about 42% of eyes in the digital group and 61% of eyes in the manual group had a rotation of 0-2° (P = 0.038). Trefoil in the manual group decreased postoperatively compared with the digital group (P = 0.012). Other aberration analyses did not reveal any statistical differences between groups.

CONCLUSIONS: Accurate slit-beam manual marking and digital image-guided marking are equally effective for toric IOL alignment.

PMID:35897093 | DOI:10.1186/s12886-022-02548-y

BMC Public Health. 2022 Jul 27;22(1):1432. doi: 10.1186/s12889-022-13826-1.

ABSTRACT

BACKGROUND: Evidence on the association between the presence of fast-food outlets and Body Mass Index (BMI) is inconsistent. Furthermore, mechanisms underlying the fast-food outlet presence-BMI association are understudied. We investigated the association between the number of fast-food outlets being present and objectively measured BMI. Moreover, we investigated to what extent this association was moderated by neighbourhood socio-economic status (NSES) and healthy food outlets. Additionally, we investigated mediation by frequency of fast-food consumption and amount of fat intake.

METHODS: In this cross-sectional study, we used baseline data of adults in Lifelines (N = 149,617). Geo-coded residential addresses were linked to fast-food and healthy food outlet locations. We computed the number of fast-food and healthy food outlets within 1 kilometre (km) of participants’ residential addresses (each categorised into null, one, or at least two). Participants underwent objective BMI measurements. We linked data to Statistics Netherlands to compute NSES. Frequency of fast-food consumption and amount of fat intake were measured through questionnaires in Lifelines. Multivariable multilevel linear regression analyses were performed to investigate associations between fast-food outlet presence and BMI, adjusting for individual and environmental potential confounders. When exposure-moderator interactions had p-value < 0.10 or improved model fit (∆AIC ≥ 2), we conducted stratified analyses. We used causal mediation methods to assess mediation.

RESULTS: Participants with one fast-food outlet within 1 km had a higher BMI than participants with no fast-food outlet within 1 km (B = 0.11, 95% CI: 0.01, 0.21). Effect sizes for at least two fast-food outlets were larger in low NSES areas (B = 0.29, 95% CI: 0.01, 0.57), and especially in low NSES areas where at least two healthy food outlets within 1 km were available (B = 0.75, 95% CI: 0.19, 1.31). Amount of fat intake, but not frequency of fast-food consumption, explained this association for 3.1%.

CONCLUSIONS: Participants living in low SES neighbourhoods with at least two fast-food outlets within 1 km of their residential address had a higher BMI than their peers with no fast-food outlets within 1 km. Among these participants, healthy food outlets did not buffer the potentially unhealthy impact of fast-food outlets. Amount of fat intake partly explained this association. This study highlights neighbourhood socio-economic inequalities regarding fast-food outlets and BMI.

PMID:35897088 | DOI:10.1186/s12889-022-13826-1

Pilot Feasibility Stud. 2022 Jul 27;8(1):158. doi: 10.1186/s40814-022-01113-0.

ABSTRACT

BACKGROUND: Persistent pain in adolescence adversely affects everyday life and is an important public health problem. The primary aim was to determine the feasibility of an 8-week app-based self-management intervention to reduce pain and improve health-related quality of life in a community-based population of adolescents with persistent pain. A secondary aim was to explore differences in health outcomes between the intervention and control groups.

METHODS: A sample of 73 adolescents aged 16-19 years with persistent pain from a community-based population were randomized into 2 groups. The intervention group received the Norwegian culturally adapted version of the iCanCope with Pain^TM app, which includes symptom tracking, goal setting, self-management strategies, and social support. The attention control group received a symptom tracking app. Feasibility was assessed as attrition rates and level of engagement (interactions with the app). The secondary outcomes included pain intensity, health-related quality of life, self-efficacy, pain self-efficacy, perceived social support from friends, anxiety and depression, and patient global impression. Statistical analyses were conducted using SPSS.

RESULTS: Demographic and baseline outcome variables did not differ between the 2 groups. No differences were found between the participants completing the study and those who withdrew. Twenty-eight adolescents completed the intervention as planned (62% attrition). Both groups had a low level of app engagement. Intention-to-treat analysis (n = 19 + 14) showed no significant differences in outcomes between groups. However, the large effect size (Cohen’s d = .9) for depression suggested a lower depression score in the intervention group.

CONCLUSIONS: High treatment attrition and low engagement indicate the need for changes in trial design in a full-scale randomized controlled trial to improve participant retention.

TRIAL REGISTRATION: The iCanCope with Pain Norway trial was retrospectively registered in Clinical Trials.gov (ID: NCT03551977 ). Registered 6 June 2018.

PMID:35897086 | DOI:10.1186/s40814-022-01113-0

Alzheimers Res Ther. 2022 Jul 27;14(1):105. doi: 10.1186/s13195-022-01048-x.

ABSTRACT

BACKGROUND: The ability of ¹⁸F-PI-2620 PET to measure the spatial distribution of tau pathology in Alzheimer’s disease (AD) has been demonstrated in previous studies. The objective of this work was to evaluate tau deposition using ¹⁸F-PI-2620 PET in beta-amyloid positive subjects with a diagnosis of mild cognitive impairment (MCI) or mild AD dementia and characterize it with respect to amyloid deposition, cerebrospinal fluid (CSF) assessment, hippocampal volume, and cognition.

METHODS: Subjects with a diagnosis of MCI due to AD or mild AD dementia and a visually amyloid-positive ¹⁸F-florbetaben PET scan (n=74, 76 ± 7 years, 38 females) underwent a baseline ¹⁸F-PI-2620 PET, T1-weighted magnetic resonance imaging (MRI), CSF assessment (Aβ42/Aβ40 ratio, p-tau, t-tau) (n=22) and several cognitive tests. A 1-year follow-up ¹⁸F-PI-2620 PET scans and cognitive assessments were done in 15 subjects.

RESULTS: Percentage of visually tau-positive scans increased with amyloid-beta deposition measured in ¹⁸F-florbetaben Centiloids (CL) (7.7% (<36 CL), 80% (>83 CL)). ¹⁸F-PI-2620 standardized uptake value ratio (SUVR) was correlated with increased ¹⁸F-florbetaben CL in several regions of interest. Elevated ¹⁸F-PI-2620 SUVR (fusiform gyrus) was associated to high CSF p-tau and t-tau (p=0.0006 and p=0.01, respectively). Low hippocampal volume was associated with increased tau load at baseline (p=0.006 (mesial temporal); p=0.01 (fusiform gyrus)). Significant increases in tau SUVR were observed after 12 months, particularly in the mesial temporal cortex, fusiform gyrus, and inferior temporal cortex (p=0.04, p=0.047, p=0.02, respectively). However, no statistically significant increase in amyloid-beta load was measured over the observation time. The MMSE (Recall score), ADAS-Cog14 (Word recognition score), and CBB (One-card learning score) showed the strongest association with tau deposition at baseline.

CONCLUSIONS: The findings support the hypothesis that ¹⁸F-PI-2620 PET imaging of neuropathologic tau deposits may reflect underlying neurodegeneration in AD with significant correlations with hippocampal volume, CSF biomarkers, and amyloid-beta load. Furthermore, quantifiable increases in ¹⁸F-PI-2620 SUVR over a 12-month period in regions with early tau deposition are consistent with the hypothesis that cortical tau is associated with cognitive impairment. This study supports the utility of ¹⁸F-PI-2620 PET to assess tau deposits in an early AD population. Quantifiable tau load and its corresponding increase in early AD cases could be a relevant target engagement marker in clinical trials of anti-amyloid and anti-tau agents.

TRIAL REGISTRATION: Data used in this manuscript belong to a tau PET imaging sub-study of the elenbecestat MissionAD Phase 3 program registered in ClinicalTrials.gov ( NCT02956486 ; NCT03036280 ).

PMID:35897078 | DOI:10.1186/s13195-022-01048-x

Crit Care. 2022 Jul 27;26(1):228. doi: 10.1186/s13054-022-04079-w.

ABSTRACT

BACKGROUND: While the Glasgow coma scale (GCS) is one of the strongest outcome predictors, the current classification of traumatic brain injury (TBI) as ‘mild’, ‘moderate’ or ‘severe’ based on this fails to capture enormous heterogeneity in pathophysiology and treatment response. We hypothesized that data-driven characterization of TBI could identify distinct endotypes and give mechanistic insights.

METHODS: We developed an unsupervised statistical clustering model based on a mixture of probabilistic graphs for presentation (< 24 h) demographic, clinical, physiological, laboratory and imaging data to identify subgroups of TBI patients admitted to the intensive care unit in the CENTER-TBI dataset (N = 1,728). A cluster similarity index was used for robust determination of optimal cluster number. Mutual information was used to quantify feature importance and for cluster interpretation.

RESULTS: Six stable endotypes were identified with distinct GCS and composite systemic metabolic stress profiles, distinguished by GCS, blood lactate, oxygen saturation, serum creatinine, glucose, base excess, pH, arterial partial pressure of carbon dioxide, and body temperature. Notably, a cluster with ‘moderate’ TBI (by traditional classification) and deranged metabolic profile, had a worse outcome than a cluster with ‘severe’ GCS and a normal metabolic profile. Addition of cluster labels significantly improved the prognostic precision of the IMPACT (International Mission for Prognosis and Analysis of Clinical trials in TBI) extended model, for prediction of both unfavourable outcome and mortality (both p < 0.001).

CONCLUSIONS: Six stable and clinically distinct TBI endotypes were identified by probabilistic unsupervised clustering. In addition to presenting neurology, a profile of biochemical derangement was found to be an important distinguishing feature that was both biologically plausible and associated with outcome. Our work motivates refining current TBI classifications with factors describing metabolic stress. Such data-driven clusters suggest TBI endotypes that merit investigation to identify bespoke treatment strategies to improve care. Trial registration The core study was registered with ClinicalTrials.gov, number NCT02210221 , registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).

PMID:35897070 | DOI:10.1186/s13054-022-04079-w

Ital J Pediatr. 2022 Jul 27;48(1):127. doi: 10.1186/s13052-022-01317-3.

ABSTRACT

According to the latest version of the Diagnostic and Statistical Manual of Mental Disorders, somatic symptom and related disorders (SSRDs) are defined as psychopathological manifestations characterized by physical signs not attributable to organic pathology. Their incidence has grown dramatically over the past few decades, and treatment is challenging. Besides other interventions on the child and the family, physiotherapy is considered an integral part of the treatment, although there is no evidence for its efficacy.The study aimed to review the available proof on the effectiveness of physiotherapy in children and adolescents with SSRDs. A systematic literature search was conducted on MEDLINE/PubMed, CINAHL, Cochrane Library, PsycINFO, and PEDro, including 1999 to 2021. The methodological quality of the publications was assessed by applying the guidelines proposed by the Equator network, according to the different study designs. The scientific bibliography on the subject was minimal and had poor methodological quality. The choice of outcome indicators and the scales to measure them varied from study to study and were not standardized, making comparison and meta-analysis challenging.Conclusion: According to the available evidence, it is impossible to answer the review question regarding the effectiveness of physiotherapy in children and adolescents with SSRDs. It is necessary to improve the methodological quality of the studies. Definition of standard rehabilitation treatments, identification of appropriate result indicators, and adoption of standardized evaluation scales are needed.

PMID:35897067 | DOI:10.1186/s13052-022-01317-3

BMC Endocr Disord. 2022 Jul 27;22(1):193. doi: 10.1186/s12902-022-01107-2.

ABSTRACT

BACKGROUND: In our previous published study, we demonstrated that a qualitatively assessed elevation in deltoid muscle echogenicity on ultrasound was both sensitive for and a strong predictor of a type 2 diabetes (T2DM) diagnosis. This study aims to evaluate if a sonographic quantitative assessment of the deltoid muscle can be used to detect T2DM.

METHODS: Deltoid muscle ultrasound images from 124 patients were stored: 31 obese T2DM, 31 non-obese T2DM, 31 obese non-T2DM and 31 non-obese non-T2DM. Images were independently reviewed by 3 musculoskeletal radiologists, blinded to the patient’s category. Each measured the grayscale pixel intensity of the deltoid muscle and humeral cortex to calculate a muscle/bone ratio for each patient. Following a 3-week delay, the 3 radiologists independently repeated measurements on a randomly selected 40 subjects. Ratios, age, gender, race, body mass index, insulin usage and hemoglobin A_1c were analyzed. The difference among the 4 groups was compared using analysis of variance or chi-square tests. Both univariate and multivariate linear mixed models were performed. Multivariate mixed-effects regression models were used, adjusting for demographic and clinical variables. Post hoc comparisons were done with Bonferroni adjustments to identify any differences between groups. The sample size achieved 90% power. Sensitivity and specificity were calculated based on set threshold ratios. Both intra- and inter-radiologist variability or agreement were assessed.

RESULTS: A statistically significant difference in muscle/bone ratios between the groups was identified with the average ratios as follows: obese T2DM, 0.54 (P < 0.001); non-obese T2DM, 0.48 (P < 0.001); obese non-T2DM, 0.42 (P = 0.03); and non-obese non-T2DM, 0.35. There was excellent inter-observer agreement (intraclass correlation coefficient 0.87) and excellent intra-observer agreements (intraclass correlation coefficient 0.92, 0.95 and 0.94). Using threshold ratios, the sensitivity for detecting T2DM was 80% (95% CI 67% to 88%) with a specificity of 63% (95% CI 50% to 75%).

CONCLUSIONS: The sonographic quantitative assessment of the deltoid muscle by ultrasound is sensitive and accurate for the detection of T2DM. Following further studies, this process could translate into a dedicated, simple and noninvasive screening method to detect T2DM with the prospects of identifying even a fraction of the undiagnosed persons worldwide. This could prove especially beneficial in screening of underserved and underrepresented communities.

PMID:35897066 | DOI:10.1186/s12902-022-01107-2