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| 2. |
- Bessa, Agustina, et al.
(author)
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Designing a Pragmatic Intervention to Help Improve the Bladder Cancer Patient Experience
- 2021
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In: Inquiry. - : Sage Publications. - 0046-9580 .- 1945-7243. ; 58
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Journal article (peer-reviewed)abstract
- Bladder cancer (BC) is the 10th most common malignancy worldwide and the patient experience is found to be worse than that for patients diagnosed with other cancer types. We aimed to develop a wellbeing intervention to help improve the bladder cancer patient experience by ameliorating their health-related Quality of Life (HRQoL). We followed the 3 phases of the modified Medical Research Council (MRC) Framework for development of complex interventions. Following a systematic review of the literature on mental, sexual, and physical wellbeing, we conducted discussion groups with patients and healthcare professionals on these 3 themes. A consultation phase was then conducted with all relevant stakeholders to co-design a wellbeing intervention as part of a feasibility study. A pragmatic wellbeing feasibility trial was designed based on the hypothesis that a wellbeing program will increase patient awareness and attendance to services available to them and will better support their needs to improve HRQoL. The primary feasibility endpoints are patient attendance to the services offered and changes in HRQoL. The principle of patient centered care has strengthened the commitment to provide a holistic approach to support BC patients. In this study, we developed a wellbeing intervention in collaboration with patients and healthcare professionals to meet an unmet need in terms of the BC patient experience.
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| 3. |
- Boateng, Irene, et al.
(author)
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Using microbiological data to improve the use of antibiotics for respiratory tract infections: A protocol for an individual patient data meta-analysis
- 2023
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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 18:11
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Journal article (peer-reviewed)abstract
- BackgroundResistance to antibiotics is rising and threatens future antibiotic effectiveness. 'Antibiotic targeting' ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence.AimTo undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs.MethodsA systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs.Trial registrationPROSPERO Registration number: CRD42023376769.
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| 4. |
- Geraghty, Adam W. A., et al.
(author)
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Internet-based vestibular rehabilitation for adults aged 50 years and over: a protocol for a randomised controlled trial
- 2014
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In: BMJ Open. - : BMJ Publishing Group: Open Access / BMJ Journals. - 2044-6055. ; 4:7, s. e005871-
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Journal article (peer-reviewed)abstract
- Introduction: Dizziness is highly prevalent in older adults and can lead to falls, fear of falling, loss of confidence, anxiety and depression. Vestibular rehabilitation (VR) exercises are effective in reducing dizziness due to vestibular dysfunction, but access to trained therapists is limited. Providing dizzy patients with booklets teaching them how to carry out VR exercises has been shown to be a cost-effective way of managing dizziness in primary care. Internet-based intervention delivery has many advantages over paper-based methods, including the provision of video instructions, automated tailoring and symptom-related feedback. This trial will examine whether an internet-based VR intervention is (1) effective in reducing dizziness and (2) a cost-effective primary care treatment option. Methods/analysis: This will be a single blind, randomised controlled trial carried out in UK primary care. A stand-alone internet-based VR intervention will be compared with routine care in 262 dizzy patients aged 50 years and over. Measures will be taken at baseline, 3 and 6 months. Our primary outcome measure will be the effectiveness of the intervention in reducing dizziness symptoms compared with routine care at 6 months. Cost-effectiveness will be examined along with the effect of the intervention on dizziness-related disability and symptoms of depression and anxiety. Psychological process variables including expectancy, self-efficacy and acceptance will be explored in relation to adherence and symptom reduction. Ethics/dissemination: This trial has undergone ethical scrutiny and been approved by an NHS Research Ethics Committee, Southampton A REC Reference: 13/SC/0119. The findings of this trial will be disseminated to the scientific community through presentations at national and international conferences, and by publishing in peer review journals. Findings will be disseminated to the public through targeted press releases. This trial will provide valuable information on the role of internet interventions in facilitating self-management in older adults.
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| 5. |
- Geraghty, Adam W. A., et al.
(author)
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Internet-Based Vestibular Rehabilitation for Older Adults With Chronic Dizziness : A Randomized Controlled Trial in Primary Care
- 2017
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In: Annals of Family Medicine. - : Annals of Family Medicine. - 1544-1709 .- 1544-1717. ; 15:3, s. 209-216
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Journal article (peer-reviewed)abstract
- PURPOSE: Vestibular rehabilitation is an effective intervention for dizziness due to vestibular dysfunction, but is seldom provided. We aimed to determine the effectiveness of an Internet-based vestibular rehabilitation program for older adults experiencing dizziness in primary care.METHODS: We undertook a single-center, single-blind randomized controlled trial comparing an Internet-based vestibular rehabilitation intervention (Balance Retraining, freely available from https://balance.lifeguidehealth.org) with usual primary care in patients from 54 primary care practices in southern England. Patients aged 50 years and older with current dizziness exacerbated by head movements were enrolled. Those in the intervention group accessed an automated Internet-based program that taught vestibular rehabilitation exercises and suggested cognitive behavioral management strategies. Dizziness was measured by the Vertigo Symptom Scale–Short Form (VSS-SF) at baseline, 3 months, and 6 months. The primary outcome was VSS-SF score at 6 months.RESULTS: A total of 296 patients were randomized in the trial; 66% were female, and the median age was 67 years. The VSS-SF was completed by 250 patients (84%) at 3 months and 230 patients (78%) at 6 months. Compared with the usual care group, the Internet-based vestibular rehabilitation group had less dizziness on the VSS-SF at 3 months (difference, 2.75 points; 95% CI, 1.39–4.12; P <.001) and at 6 months (difference, 2.26 points; 95% CI, 0.39–4.12; P = .02, respectively). Dizziness-related disability was also lower in the Internet-based vestibular rehabilitation group at 3 months (difference, 6.15 points; 95% CI, 2.81–9.49; P <.001) and 6 months (difference, 5.58 points; 95% CI, 1.19–10.0; P = .01).CONCLUSIONS: Internet-based vestibular rehabilitation reduces dizziness and dizziness-related disability in older primary care patients without requiring clinical support. This intervention has potential for wide application in community settings.
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| 6. |
- Heinz, Judith, et al.
(author)
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Strategies to reduce antibiotic use in women with uncomplicated urinary tract infection in primary care : protocol of a systematic review and meta-analysis including individual patient data
- 2020
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 10:10
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Research review (peer-reviewed)abstract
- Introduction: Uncomplicated urinary tract infection (UTI) in women is a common reason to present in general practice and is usually treated with antibiotics to reduce symptom severity and duration. Results of recent clinical trials indicate that non-antibiotic treatment approaches can also be effective. However, it remains unclear which patients would benefit from antibiotic treatment and which can effectively and safely be treated without antibiotics. This systematic review and meta-analysis aims to estimate the effect of treatment strategies to reduce antibiotic use in comparison with immediate antibiotic treatment and to identify prognostic factors and moderators of treatment effects. A further aim is to identify subgroups of patients benefiting from a specific therapy.Methods and analysis: A systematic literature search will be performed to identify randomised controlled trials which investigated the effect of treatment strategies to reduce antibiotic use in female adults with uncomplicated UTI compared with immediate antibiotic treatment. Therefore, the primary outcome of the meta-analysis is incomplete recovery. Anonymised individual patient data (IPD) will be collected. Aggregate data will be used for pairwise comparisons of treatment strategies using meta-analysis models with random effects accounting for potential between-study heterogeneity. Potential effect moderators will be explored in meta-regressions. For IPD, generalised linear mixed models will be used, which may be adjusted for baseline characteristics. Interactions of baseline variables with treatment effects will be explored. These models will be used to assess direct comparisons of treatment, but might be extended to networks.Ethics and dissemination: The local institutional review and ethics board judged the project a secondary analysis of existing anonymous data which meet the criteria for waiver of ethics review. Dissemination of the results will be via published scientific papers and presentations. Key messages will be promoted for example, via social media or press releases.
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| 7. |
- Kaußner, Yvonne, et al.
(author)
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Reducing antibiotic use in uncomplicated urinary tract infections in adult women : a systematic review and individual participant data meta-analysis
- 2022
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In: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 28:12, s. 1558-1566
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Research review (peer-reviewed)abstract
- Background: Randomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics, and placebo to prevent overprescription of antibiotics in women with uncomplicated urinary tract infections (uUTI).Objectives: To estimate the effect of these strategies and to identify symptoms, signs, or other factors that indicate a benefit from these strategies.Data sources: MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Database of Systematic Reviews and of Controlled Trials, and ClinicalTrials.Study eligibility criteria, participants and interventions: RCTs investigating any strategies to reduce antibiotics vs. immediate antibiotics in adult women with uUTI in primary care.Methods: We extracted individual participant data (IPD) if available, otherwise aggregate data (AD). Bayesian random-effects meta-analysis of the AD was used for pairwise comparisons. Candidate moderators and prognostic indicators of treatment effects were investigated using generalised linear mixed models based on IPD.Results: We analysed IPD of 3524 patients from eight RCTs and AD of 78 patients. Non-antibiotic strategies increased the rates of incomplete recovery (OR 3.0; 95% credible interval (CrI), 1.7–5.5; Bayesian p-value (pB) = 0.0017; τ = 0.6), subsequent antibiotic treatment (OR 3.5; 95% CrI, 2.1–5.8; pB = 0.0003) and pyelonephritis (OR 5.6; 95% CrI, 2.3–13.9; pB = 0.0003). Conversely, they decreased overall antibiotic use by 63%.Patients positive for urinary erythrocytes and urine culture were at increased risk for incomplete recovery (OR 4.7; 95% CrI, 2.1–10.8; pB = 0.0010), but no difference was apparent where both were negative (OR 0.8; 95% CrI, 0.3–2.0; pB = 0.667). In patients treated using non-antibiotic strategies, urinary erythrocytes and positive urine culture were independent prognostic indicators for subsequent antibiotic treatment and pyelonephritis.Conclusions: Compared to immediate antibiotics, non-antibiotic strategies reduce overall antibiotic use but result in poorer clinical outcomes. The presence of erythrocytes and tests to confirm bacteria in urine could be used to target antibiotic prescribing.
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| 8. |
- Little, Paul, et al.
(author)
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Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial
- 2013
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In: The Lancet - Infectious diseases. - : Elsevier: Lancet. - 1473-3099 .- 1474-4457. ; 13:2, s. 123-129
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Journal article (peer-reviewed)abstract
- Background Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older. less thanbrgreater than less thanbrgreater thanMethods Patients older than 18 years with acute lower-respiratory-tract infections (cough of andlt;= 28 days duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated "moderately bad" or worse. Secondary outcomes were symptom severity in days 2-4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N). less thanbrgreater than less thanbrgreater thanFindings 1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated "moderately bad" or worse (hazard ratio 1.06, 95% CI 0.96-1.18; p=0.229) nor mean symptom severity (1.69 with placebo vs 1.62 with amoxicillin; difference 0.07 [95% CI -0.15 to 0.007]; p=0.074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 [15.9%] of 1021 patients vs 194 [19.3%] of 1006; p=0-043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxidllin group than in the placebo group (number needed to harm 21,95% CI 11-174; p=0.025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the ammdcillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of selective benefit in patients aged 60 years or older (n=595). less thanbrgreater than less thanbrgreater thanInterpretation When pneumonia is not suspected clinically, amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more, and causes slight harms. less thanbrgreater than less thanbrgreater thanFunding European Commission Framework Programme 6, UK National Institute for Health Research, Barcelona Ciberde Enfermedades Respiratorias, and Research Foundation Flanders.
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| 9. |
- Naghavi, Mohsen, et al.
(author)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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In: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
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Journal article (peer-reviewed)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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| 10. |
- Zheng, Hou-Feng, et al.
(author)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Journal article (peer-reviewed)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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