5366 research outputs found
Sort by
Accuracy of Peridialytic, Intradialytic, and Scheduled Interdialytic Recordings in Detecting Elevated Ambulatory Blood Pressure in Hemodialysis Patients.
No full textRATIONALE AND OBJECTIVE
Current recommendations suggest the use of ambulatory-BP-monitoring (ABPM) as the gold-standard for hypertension diagnosis and management in hemodialysis patients. This study assesses the accuracy of peridialytic, intradialytic, and scheduled interdialytic recordings in detecting abnormally elevated 44-h interdialytic BP.
STUDY DESIGN
Diagnostic test study.
SETTINGS AND PARTICIPANTS
242 Greek hemodialysis patients who successfully underwent ABPM.
TESTS COMPARED
Ambulatory BP was used as reference to evaluate the accuracy of following BP metrics: pre- and post-dialysis, intradialytic, intradialytic plus pre/post-dialysis, and scheduled interdialytic BP at off-dialysis day at 8:00 am, 8:00 pm, and their average.
OUTCOME
44-h ambulatory SBP/DBP ≥130/80 mmHg.
RESULTS
44-h SBP/DBP levels differed significantly from pre- and post-dialysis BP, but showed no or minor differences compared to the other BP metrics. Bland-Altman plots showed absence of systematic bias for all metrics, but large between-method difference and wider 95% limits of agreement for pre- and post-dialysis BP compared to intradialytic, intradialytic plus pre/post-dialysis and averaged scheduled interdialytic BP. The sensitivity/specificity and κ-statistic for diagnosing 44-h SBP≥130 mmHg were low for pre-dialysis (86.5%/38.6%, κ-statistic=0.27) and post-dialysis BP (63.1%/73.3%, κ-statistic=0.35), but better for intradialytic (77.3%/76.2%, κ-statistic=0.53), intradialytic plus pre/post-dialysis (76.6%/72.3%, κ-statistic=0.49), and scheduled interdialytic BP (87.9%/77.2%, κ-statistic=0.66). In ROC-analyses, the Areas-Under-the-Curve (AUC) of pre-dialysis (AUC 0.723) and post-dialysis SBP (AUC 0.746) were significantly lower than that of intradialytic (AUC 0.850), intradialytic plus pre/post-dialysis (AUC 0.850) and scheduled interdialytic SBP (AUC 0.917) (z-test, p<0.001 for all pairwise comparisons). Similar observations were made for DBP.
LIMITATIONS
Typical home BP data were not obtained and no assessment was obtained of reproducibility of examined metrics over time.
CONCLUSIONS
Intradialytic, intradialytic plus pre/post-dialysis, and scheduled interdialytic BP measurements were more accurate in detecting elevated 44-h BP than pre- and post-dialysis BP. Averaged intradialytic BP recordings or scheduled readings at the off-dialysis day appear to be promising approaches to the diagnosis of elevated BP in hemodialysis
COVID-19-related health anxieties and impact of specific interventions in patients with inflammatory bowel disease in the UK.
No full textObjective
Health-related concerns brought on by the COVID-19 pandemic and the impact of specific local and national interventions have not been explored in patients with inflammatory bowel disease (IBD) in the UK. We evaluated perspectives of patients with IBD on the pandemic and effectiveness of information dissemination in addressing concerns.
Methods
We prospectively conducted a survey among patients with IBD during the COVID-19 pandemic to assess concerns, information-seeking behaviours, risk perception, compliance and effect of specific interventions.
Results
A total of 228 patients were interviewed of whom 89% reported being concerned about the impact of COVID-19 on their health. Access to at least one IBD-specific clinical interaction during the pandemic (COVID-19 information letter from IBD team, interaction with IBD team or general practitioner, Crohn and Colitis UK website visit) was significantly associated with alleviating concerns (OR 2.66; 95% CI 1.35 to 5.24; p=0.005). Seeking health information solely through unofficial channels (search engines or social media) was less likely to ease concerns (OR 0.15; 95% CI 0.03 to 0.61; p=0.008). A quarter of patients disagreed with their assigned risk groups, with majority perceiving higher-risk profiles. This discordance was greatest in patients within the moderate-risk group and constituted immunosuppression use. Nearly 40% of patients had ongoing concerns with regard to their medications of whom a third felt their concerns were not addressed.
Conclusion
IBD-specific clinical interactions are associated with alleviation of COVID-19 health concerns. These findings have wider implications and emphasise importance of innovative solutions that facilitate effective communication with patients without overburdening current services
Diagnostic accuracy of loop mediated isothermal amplification coupled to nanopore sequencing (LamPORE) for the detection of SARS-CoV-2 infection at scale in symptomatic and asymptomatic populations.
No full textOBJECTIVES
Rapid, high throughput diagnostics are a valuable tool, allowing the detection of SARS-CoV-2 in populations, in order to identify and isolate people with asymptomatic and symptomatic infections. Reagent shortages and restricted access to high throughput testing solutions have limited the effectiveness of conventional assays such as reverse transcriptase quantitative PCR (RT-qPCR), particularly throughout the first months of the COVID-19 pandemic. We investigated the use of LamPORE, where loop mediated isothermal amplification (LAMP) is coupled to nanopore sequencing technology, for the detection of SARS-CoV-2 in symptomatic and asymptomatic populations.
METHODS
In an asymptomatic prospective cohort, for three weeks in September 2020 health care workers across four sites (Birmingham, Southampton, Basingstoke and Manchester) self-swabbed with nasopharyngeal swabs weekly and supplied a saliva specimen daily. These samples were tested for SARS-CoV-2 RNA using the Oxford Nanopore LamPORE system and a reference RT-qPCR assay on extracted sample RNA. A second retrospective cohort of 848 patients with influenza like illness from March 2020 - June 2020, were similarly tested from nasopharyngeal swabs.
RESULTS
In the asymptomatic cohort a total of 1200 participants supplied 23,427 samples (3,966 swab, 19,461 saliva) over a three-week period. The incidence of SARS-CoV-2 detection using LamPORE was 0.95%. Diagnostic sensitivity and specificity of LamPORE was >99.5% (reducing to ∼ 98% when clustered estimation was used) in both swab and saliva asymptomatic samples when compared to the reference RT-qPCR test. In the retrospective symptomatic cohort, the incidence was 13.4% and the sensitivity and specificity were 100%.
CONCLUSIONS
LamPORE is a highly accurate methodology for the detection of SARS-CoV-2 in both symptomatic and asymptomatic population settings and can be used as an alternative to RT-qPCR
Mobilization in the evening to prevent delirium: A pilot randomized trial.
No full textBACKGROUND
Delirium is a common complication in patients in Intensive Care Units (ICU). Interventions such as mobilization are effective in the prevention and treatment of delirium, although this is usually completed during the daytime.
AIM
The aim of this study was to assess the feasibility of mobilization in the evening to prevent and treat ICU patients from delirium by an additional mobility team over 2 weeks.
METHODS
The design was a pilot, multi-centre, randomized, controlled trial in four mixed ICUs over a period of 2 weeks. The mobility team consisted of trained nurses and physiotherapists. Patients in the intervention group were mobilized onto the edge of the bed or more between 21.00 and 23.00. Patients in the control group received usual care. The primary outcome parameter was the feasibility of the study, measured as recruitment rate, delivery rate, and safety. Secondary outcomes were duration and incidence of delirium, mortality, duration of mechanical ventilation (MV), and hospital length of stay for 28 days follow-up, and power calculation for a full trial.
RESULTS
Out of 185 patients present in the ICUs, 28.6% (n = 53) were eligible and could be recruited, of which 24.9% (n = 46, Intervention = 26, Control = 20) were included in the final analysis. In the intervention group, mobilization could be delivered in 75% (n = 54) of 72 possible occasions; mobilization-related safety events appeared in 16.7% (n = 9) without serious consequences. Secondary parameters were similar, with less delirium in the intervention group albeit not significant. With an association of Cramer's V = 0.237, a complete study reaching statistical significance would require at least 140 patients, last 6 weeks, and cost >30 000 €.
CONCLUSIONS
In a mixed ICU population, mobilization in the evening was feasible in one-quarter of patients with a low rate of safety events. Future trials seem to be feasible and worth conducting
Targeting synovial fibroblast proliferation in rheumatoid arthritis (TRAFIC): an open-label, dose-finding, phase 1b trial.
No full textBackground
Current rheumatoid arthritis therapies target immune inflammation and are subject to ceiling effects. Seliciclib is an orally available cyclin-dependent kinase inhibitor that suppresses proliferation of synovial fibroblasts-cells not yet targeted in rheumatoid arthritis. Part 1 of this phase 1b/2a trial aimed to establish the maximum tolerated dose of seliciclib in patients with active rheumatoid arthritis despite ongoing treatment with TNF inhibitors, and to evaluate safety and pharmacokinetics.
Methods
Phase 1b of the TRAFIC study was a non-randomised, open-label, dose-finding trial done in rheumatology departments in five UK National Health Service hospitals. Eligible patients (aged ≥18 years) fulfilled the 1987 American College of Rheumatology (ACR) or the 2010 ACR-European League Against Rheumatism classification criteria for rheumatoid arthritis and had moderate to severe disease activity (a Disease Activity Score for 28 joints [DAS28] of ≥3·2) despite stable treatment with anti-TNF therapy for at least 3 months before enrolment. Participants were recruited sequentially to a maximum of seven cohorts of three participants each, designated to receive seliciclib 200 mg, 400 mg, 600 mg, 800 mg, or 1000 mg administered in 200 mg oral capsules. Sequential cohorts received doses determined by a restricted, one-stage Bayesian continual reassessment model, which determined the maximum tolerated dose (the primary outcome) based on a target dose-limiting toxicity rate of 35%. Seliciclib maximum concentration (C) and area under the plasma concentration time curve 0-6 h (AUC) were measured. This study is registered with ISRCTN, ISRCTN36667085.
Findings
Between Oct 8, 2015, and Aug 15, 2017, 37 patients were screened and 15 were enrolled to five cohorts and received seliciclib, after which the trial steering committee and the data monitoring committee determined that the maximum tolerated dose could be defined. In addition to a TNF inhibitor, ten (67%) enrolled patients were taking conventional synthetic disease modifying antirheumatic drugs. The maximum tolerated dose of seliciclib was 400 mg, with an estimated dose-limiting toxicity probability of 0·35 (90% posterior probability interval 0·18-0·52). Two serious adverse events occurred (one acute kidney injury in a patient receiving the 600 mg dose and one drug-induced liver injury in a patient receiving the 400 mg dose), both considered to be related to seliciclib and consistent with its known safety profile. 65 non-serious adverse events occurred during the trial, 50 of which were considered to be treatment related. Most treatment-related adverse events were mild; 20 of the treatment-related non-serious adverse events contributed to dose-limiting toxicities. There were no deaths. Average C and AUC were two-times higher in participants developing dose-limiting toxicities.
Interpretation
The maximum tolerated dose of seliciclib has been defined for rheumatoid arthritis refractory to TNF blockade. No unexpected safety concerns were identified to preclude ongoing clinical evaluation in a formal efficacy trial.
Funding
UK Medical Research Council, Cyclacel, Research into Inflammatory Arthritis Centre (Versus Arthritis), and the National Institute of Health Research Newcastle and Birmingham Biomedical Research Centres and Clinical Research Facilities
Fostering healthy aging: The interdependency of infections, immunity and frailty.
No full textUntangling the interdependency of infections, immunity and frailty may help to clarify their roles in the maintenance of health in aging individuals, and the recent COVID-19 pandemic has further highlighted such priority. In this scoping review we aimed to systematically collect the evidence on 1) the impact of common infections such as influenza, pneumonia and varicella zoster on frailty development, and 2) the role played by frailty in the response to immunization of older adults. Findings are discussed under a unifying framework to identify knowledge gaps and outline their clinical and public health implications to foster a healthier aging. Twenty-nine studies (113,863 participants) selected to answer the first question provided a moderately strong evidence of an association between infections and physical as well as cognitive decline - two essential dimensions of frailty. Thirteen studies (34,520 participants) investigating the second aim, showed that frailty was associated with an impaired immune response in older ages, likely due to immunosenescence. However, the paucity of studies, the absence of tools to predict vaccine efficacy, and the lack of studies investigating the efficacy of newer vaccines in presence of frailty, strongly limit the formulation of more personalized immunization strategies for older adults. The current evidence suggests that infections and frailty repeatedly cross each other pathophysiological paths and accelerate the aging process in a vicious circle. Such evidence opens to several considerations. First, the prevention of both conditions pass through a life course approach, which includes several individual and societal aspects. Second, the maintenance of a well-functioning immune system may be accomplished by preventing frailty, and vice versa. Third, increasing the adherence to immunization may delay the onset of frailty and maintain the immune system homeostasis, beyond preventing infections
Exploring young people's preferences for STI screening in the UK: A qualitative study and discrete choice experiment.
No full textINTRODUCTION
Stigma remains a key issue for many health screening interventions such as screening for sexually transmitted infections (STIs). Young people continue to experience the greatest burden of STI infection. In order to increase uptake, screening services need to be more patient-focused. This study sought to examine young people's preferences for sexual health screening to understand how scarce public health resources can optimise screening uptake.
METHODS
This study involved both qualitative and quantitative components. Focus groups and individual interviews were undertaken with young people aged 16-24 recruited from community settings and a specialist clinic. Themes which emerged from the focus groups were used to inform the design of a discrete choice experiment (DCE). A questionnaire survey (incorporating the DCE) was conducted with members of an internet panel, with over-sampling of black, Asian and minority ethnic groups.
RESULTS
Overall, 41 participants took part in eight focus groups and two in individual interviews. Six major themes emerged as important when making decisions about STI screening - stigma and embarrassment; knowledge about STIs and risk; where to get tested; how staff would treat them; what STIs to be tested for; and convenience (waiting times). Overall, 1946 participants took part in the survey. The DCE results revealed that the most important factors for young people are that all STIs are tested for, and that staff attitude is non-judgemental. The results also suggest that there is a preference for screening in specialist clinics and for full appointments over limited ones. Although respondents preferred shorter time periods for appointments and results, other 'process' factors were also important.
CONCLUSION
This study demonstrates that by combining qualitative and quantitative methods, a richer understanding of STI screening preferences is possible. The findings show that comprehensive testing and a perceived 'non-judgemental' attitude are particularly important to young people, as well as convenience
Effects of short-term graded dietary carbohydrate intake on intramuscular and whole-body metabolism during moderate-intensity exercise.
No full textAltering dietary carbohydrate (CHO) intake modulates fuel utilization during exercise. However, there has been no systematic evaluation of metabolic responses to graded changes in short-term (< 1 week) dietary CHO intake. Thirteen active men performed interval running exercise combined with isocaloric diets over 3 days before evaluation of metabolic responses to 60-min running at 65% V̇Omax on three occasions. Diets contained lower (LOW, 2.40 ± 0.66 g CHO.kg.d, 21.3 ± 0.5% of energy intake [EI]), moderate (MOD, 4.98 ± 1.31 g CHO.kg.d, 46.3 ± 0.7% EI), or higher (HIGH, 6.48 ± 1.56 g CHO.kg.d, 60.5 ± 1.6% EI) CHO. Pre-exercise muscle glycogen content was lower in LOW (54.3 ± 26.4 mmol.kg wet weight [ww]) compared to MOD (82.6 ± 18.8 mmol.kg ww) and HIGH (80.4 ± 26.0 mmol.kg ww, P<0.001; MOD vs. HIGH, P=0.85). Whole-body substrate oxidation, systemic responses, and muscle substrate utilization during exercise indicated increased fat and decreased CHO metabolism in LOW (RER: 0.81 ± 0.01) compared to MOD (RER 0.86 ± 0.01, P = 0.0005) and HIGH (RER: 0.88 ± 0.01, P < 0.0001; MOD vs. HIGH, P=0.14). Higher basal muscle expression of genes encoding proteins implicated in fat utilization was observed in LOW. In conclusion, muscle glycogen availability and subsequent metabolic responses to exercise were resistant to increases in dietary CHO intake from ~5.0 to ~6.5 g CHO.kg.d (46% to 61% EI), while muscle glycogen, gene expression and metabolic responses were sensitive to more marked reductions in CHO intake (~2.4 g CHO.kg.d, ~21% EI)
Differences in presentation, severity and management of DKA in type 1 and type 2 diabetes during the COVID-19 pandemic.
No full textCurrent Perspectives on Idiopathic Intracranial Hypertension without Papilloedema.
No full textThe pseudotumor cerebri syndrome embraces disorders characterised by raised intracranial pressure, where the commonest symptom is headache (90%). Idiopathic intracranial hypertension without papilloedema (IIHWOP) is increasingly recognised as a source of refractory headache symptoms and resultant neurological disability. Although the majority of patients with IIHWOP are phenotypically similar to those with idiopathic intracranial hypertension (IIH), it remains uncertain as to whether IIHWOP is nosologically distinct from IIH. The incidence, prevalence, and the degree of association with the world-wide obesity epidemic is unknown. Establishing a diagnosis of IIHWOP can be challenging, as often lumbar puncture is not routinely part of the work-up for refractory headaches. There are published diagnostic criteria for IIHWOP; however, some report uncertainty regarding a pathologically acceptable cut off for a raised lumbar puncture opening pressure, which is a key criterion. The literature provides little information to help guide clinicians in managing patients with IIHWOP. Further research is therefore needed to better understand the mechanisms that drive the development of chronic daily headaches and a relationship to intracranial pressure; and indeed, whether such patients would benefit from therapies to lower intracranial pressure. The aim of this narrative review was to perform a detailed search of the scientific literature and provide a summary of historic and current opinion regarding IIHWOP