GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Material
Language
Subjects(RVK)
  • 1
    In: Nature, Springer Science and Business Media LLC, Vol. 607, No. 7917 ( 2022-07-07), p. 97-103
    Abstract: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care 1 or hospitalization 2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling ( IL10RB and PLSCR1 ), leucocyte differentiation ( BCL11A ) and blood-type antigen secretor status ( FUT2 ). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase ( ATP11A ), and increased expression of a mucin ( MUC1 )—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules ( SELE , ICAM5 and CD209 ) and the coagulation factor F8 , all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    RVK:
    RVK:
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    In: Research Methods in Medicine & Health Sciences, SAGE Publications, Vol. 4, No. 1 ( 2023-01), p. 2-15
    Abstract: To test the feasibility of undertaking a simultaneous Study Within A Trial (SWAT) to train staff who recruit participants into surgical randomised controlled trials (RCTs), by assessing key uncertainties around recruitment, randomisation, intervention delivery and data collection. Study design and setting Twelve surgical RCTs were eligible. Interested sites (clusters) were randomised 1:1, with recruiting staff (surgeons and nurses) offered training or no training. The primary outcome was the feasibility of recruiting sites across multiple surgical trials simultaneously. Secondary outcomes included numbers/types of staff enrolled, attendance at training, training acceptability, confidence in recruiting and participant recruitment rates six months later. Results Four RCTs (33%) comprising 91 sites participated. Of these, 29 sites agreed to participate (32%) and were randomised to intervention (15 sites, 29 staff) or control (14 sites, 29 staff). Research nurses attended and found the training to be acceptable; no surgeons attended. In the intervention group, there was evidence of increased confidence when pre- and post- training scores were compared (mean difference in change 1.42; 95% CI 0.56, 2.27; p = 0.002). There was no effect on recruitment rate. Conclusion It was feasible to randomise sites across four surgical RCTs in a simultaneous SWAT design. However, as small numbers of trials and sites participated, and no surgeons attended training, strategies to improve these aspects are needed for future evaluations.
    Type of Medium: Online Resource
    ISSN: 2632-0843 , 2632-0843
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 3053282-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Annals of Surgery Vol. 246, No. 6 ( 2007-12), p. 1104-1109
    In: Annals of Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 246, No. 6 ( 2007-12), p. 1104-1109
    Type of Medium: Online Resource
    ISSN: 0003-4932
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 2002200-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: Health Technology Assessment, National Institute for Health and Care Research, Vol. 25, No. 46 ( 2021-7), p. 1-118
    Abstract: Falls and fall-related fractures are highly prevalent among older people and are a major contributor to morbidity and costs to individuals and society. Only one small pilot trial has evaluated the effectiveness of a home hazard assessment and environmental modification in the UK. This trial reported a reduction in falls as a secondary outcome, and no economic evaluation was undertaken. Therefore, the results need to be confirmed and a cost-effectiveness analysis needs to be undertaken. Objective To determine the clinical effectiveness and cost-effectiveness of a home hazard assessment and environmental modification delivered by occupational therapists for preventing falls among community-dwelling people aged ≥ 65 years who are at risk of falling, relative to usual care. Design This was a pragmatic, multicentre, modified cohort randomised controlled trial with an economic evaluation and a qualitative study. Setting Eight NHS trusts in primary and secondary care in England. Participants In total, 1331 participants were randomised (intervention group, n  = 430; usual-care group, n  = 901) via a secure, remote service. Blinding was not possible. Interventions All participants received a falls prevention leaflet and routine care from their general practitioner. The intervention group were additionally offered one home environmental assessment and modifications recommended or provided to identify and manage personal fall-related hazards, delivered by an occupational therapist. Main outcome measures The primary outcome was the number of falls per participant during the 12 months from randomisation. The secondary outcomes were the proportion of fallers and multiple fallers, time to fall, fear of falling, fracture rate, health-related quality of life and cost-effectiveness. Results The primary analysis included all 1331 randomised participants and indicated weak evidence of a difference in fall rate between the two groups, with an increase in the intervention group relative to usual care (adjusted incidence rate ratio 1.17, 95% confidence interval 0.99 to 1.38; p  = 0.07). A similar proportion of participants in the intervention group (57.0%) and the usual-care group (56.2%) reported at least one fall over 12 months. There were no differences in any of the secondary outcomes. The base-case cost-effectiveness analysis from an NHS and Personal Social Services perspective found that, on average per participant, the intervention was associated with additional costs (£18.78, 95% confidence interval £16.33 to £21.24), but was less effective (mean quality-adjusted life-year loss –0.0042, 95% confidence interval –0.0041 to –0.0043). Sensitivity analyses demonstrated uncertainty in these findings. No serious, related adverse events were reported. The intervention was largely delivered as intended, but recommendations were followed to a varying degree. Limitations Outcome data were self-reported by participants, which may have led to inaccuracies in the reported falls data. Conclusions We found no evidence that an occupational therapist-delivered home assessment and modification reduced falls in this population of community-dwelling participants aged ≥ 65 years deemed at risk of falling. The intervention was more expensive and less effective than usual care, and therefore it does not provide a cost-effective alternative to usual care. Future work An evaluation of falls prevention advice in a higher-risk population, perhaps those previously hospitalised for a fall, or given by other professional staff could be justified. Trial registration Current Controlled Trials ISRCTN22202133. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 46. See the NIHR Journals Library website for further project information.
    Type of Medium: Online Resource
    ISSN: 1366-5278 , 2046-4924
    Language: English
    Publisher: National Institute for Health and Care Research
    Publication Date: 2021
    detail.hit.zdb_id: 2059206-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    In: Trials, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2013-12)
    Abstract: Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain. Methods/design HERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis. Discussion The HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting. Trial registration ISRCTN91859104 .
    Type of Medium: Online Resource
    ISSN: 1745-6215
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 2040523-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 6
    In: Gerontology, S. Karger AG, Vol. 64, No. 5 ( 2018), p. 503-512
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Falls are a major cause of morbidity among older people. Multifaceted interventions may be effective in preventing falls and related fractures. 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 To evaluate the cost-effectiveness alongside the REducing Falls with Orthoses and a Multifaceted podiatry intervention (REFORM) trial. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 REFORM was a pragmatic multicentre cohort randomised controlled trial in England and Ireland; 1,010 participants ( & #x3e; 65 years) were randomised to receive either a podiatry intervention ( 〈 i 〉 n 〈 /i 〉 = 493), including foot and ankle strengthening exercises, foot orthoses, new footwear if required, and a falls prevention leaflet, or usual podiatry treatment plus a falls prevention leaflet ( 〈 i 〉 n 〈 /i 〉 = 517). Primary outcome: incidence of falls per participant in the 12 months following randomisation. Secondary outcomes: proportion of fallers and quality of life (EQ-5D-3L) which was converted into quality-adjusted life years (QALYs) for each participant. Differences in mean costs and QALYs at 12 months were used to assess the cost-effectiveness of the intervention relative to usual care. Cost-effectiveness analyses were conducted in accordance with National Institute for Health and Clinical Excellence reference case standards, using a regression-based approach with costs expressed in GBP (2015 price). The base case analysis used an intention-to-treat approach on the imputed data set using multiple imputation. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 There was a small, non-statistically significant reduction in the incidence rate of falls in the intervention group (adjusted incidence rate ratio 0.88, 95% CI 0.73–1.05, 〈 i 〉 p 〈 /i 〉 = 0.16). Participants allocated to the intervention group accumulated on average marginally higher QALYs than the usual care participants (mean difference 0.0129, 95% CI –0.0050 to 0.0314). The intervention costs were on average GBP 252 more per participant compared to the usual care participants (95% CI GBP –69 to GBP 589). Incremental cost-effectiveness ratios ranged between GBP 19,494 and GBP 20,593 per QALY gained, below the conventional National Health Service cost-effectiveness thresholds of GBP 20,000 to GBP 30,000 per additional QALY. The probability that the podiatry intervention is cost-effective at a threshold of GBP 30,000 per QALY gained was 0.65. The results were robust to sensitivity analyses. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The benefits of the intervention justified the moderate cost. The intervention could be a cost-effective option for falls prevention when compared with usual care in the UK.
    Type of Medium: Online Resource
    ISSN: 0304-324X , 1423-0003
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
    detail.hit.zdb_id: 1482689-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    Online Resource
    Online Resource
    Elsevier BV ; 2011
    In:  Journal of Affective Disorders Vol. 128, No. 1-2 ( 2011-01), p. 72-82
    In: Journal of Affective Disorders, Elsevier BV, Vol. 128, No. 1-2 ( 2011-01), p. 72-82
    Type of Medium: Online Resource
    ISSN: 0165-0327
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 1500487-9
    SSG: 12
    SSG: 5,2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 8
    In: Annals of Internal Medicine, American College of Physicians, Vol. 155, No. 9 ( 2011-11-01), p. 569-
    Type of Medium: Online Resource
    ISSN: 0003-4819
    RVK:
    Language: English
    Publisher: American College of Physicians
    Publication Date: 2011
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 9
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 12, No. 1 ( 2017-1-20), p. e0168712-
    Type of Medium: Online Resource
    ISSN: 1932-6203
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2017
    detail.hit.zdb_id: 2267670-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 10
    In: Health Technology Assessment, National Institute for Health and Care Research, Vol. 21, No. 24 ( 2017-04), p. 1-198
    Abstract: Falls are a serious cause of morbidity and cost to individuals and society. Evidence suggests that foot problems and inappropriate footwear may increase the risk of falling. Podiatric interventions could help reduce falls; however, there is limited evidence regarding their clinical effectiveness and cost-effectiveness. Objectives To determine the clinical effectiveness and cost-effectiveness of a multifaceted podiatry intervention for preventing falls in community-dwelling older people at risk of falling, relative to usual care. Design A pragmatic, multicentred, cohort randomised controlled trial with an economic evaluation and qualitative study. Setting Nine NHS trusts in the UK and one site in Ireland. Participants In total, 1010 participants aged ≥ 65 years were randomised (intervention, n  = 493; usual care, n  = 517) via a secure, remote service. Blinding was not possible. Interventions All participants received a falls prevention leaflet and routine care from their podiatrist and general practitioner. The intervention also consisted of footwear advice, footwear provision if required, foot orthoses and foot- and ankle-strengthening exercises. Main outcome measures The primary outcome was the incidence rate of falls per participant in the 12 months following randomisation. The secondary outcomes included the proportion of fallers and multiple fallers, time to first fall, fear of falling, fracture rate, health-related quality of life (HRQoL) and cost-effectiveness. Results The primary analysis consisted of 484 (98.2%) intervention and 507 (98.1%) usual-care participants. There was a non-statistically significant reduction in the incidence rate of falls in the intervention group [adjusted incidence rate ratio 0.88, 95% confidence interval (CI) 0.73 to 1.05; p  = 0.16]. The proportion of participants experiencing a fall was lower (50% vs. 55%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00; p  = 0.05). No differences were observed in key secondary outcomes. No serious, unexpected and related adverse events were reported. The intervention costs £252.17 more per participant (95% CI –£69.48 to £589.38) than usual care, was marginally more beneficial in terms of HRQoL measured via the EuroQoL-5 Dimensions [mean quality-adjusted life-year (QALY) difference 0.0129, 95% CI –0.0050 to 0.0314 QALYs] and had a 65% probability of being cost-effective at the National Institute for Health and Care Excellence threshold of £30,000 per QALY gained. The intervention was generally acceptable to podiatrists and trial participants. Limitations Owing to the difficulty in calculating a sample size for a count outcome, the sample size was based on detecting a difference in the proportion of participants experiencing at least one fall, and not the primary outcome. We are therefore unable to confirm if the trial was sufficiently powered for the primary outcome. The findings are not generalisable to patients who are not receiving podiatry care. Conclusions The intervention was safe and potentially effective. Although the primary outcome measure did not reach significance, a lower fall rate was observed in the intervention group. The reduction in the proportion of older adults who experienced a fall was of borderline statistical significance. The economic evaluation suggests that the intervention could be cost-effective. Future work Further research could examine whether or not the intervention could be delivered in group sessions, by physiotherapists, or in high-risk patients. Trial registration Current Controlled Trials ISRCTN68240461. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 24. See the NIHR Journals Library website for further project information.
    Type of Medium: Online Resource
    ISSN: 1366-5278 , 2046-4924
    Language: English
    Publisher: National Institute for Health and Care Research
    Publication Date: 2017
    detail.hit.zdb_id: 2059206-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...