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Background The optimal diagnostic pathway for prostate cancer (PCa) is evolving, requiring further evaluation in a randomized controlled trial. Purpose To assess the diagnostic accuracy of prebiopsy multiparametric MRI in the identification of clinically significant PCa (csPCa) using radical prostatectomy (RP) specimens as the reference standard, and to test the diagnostic accuracy of combined US and MRI fusion-targeted biopsy with systematic biopsies. Materials and Methods In a prospective randomized controlled trial including university hospitals, men with suspected PCa were recruited between January 2015 and August 2020 to assess the diagnostic accuracy of multiparametric MRI before biopsy in detection of csPCa at biopsy and RP histopathologic structure (primary outcome). Men with lesions suspicious for cancer (Prostate Imaging and Reporting Data System [PI-RADS] ≥3) at multiparametric MRI were first randomized to either systematic random prostate biopsies alone (control group) or US and MRI fusion-targeted biopsies with systematic random prostate biopsies (intervention group) at a one-to-one ratio to compare the diagnostic accuracy of systematic random versus combined fusion with systematic random biopsies (secondary outcome). A subset of recruited participants (n = 89) underwent RP and histologic sectioning. Results There were 582 participants who were eligible to undergo multiparametric MRI (mean age, 65 years ± 6 [SD]). In total, 413 had a PI-RADS score of at least 3 and were randomized into either the intervention group (207 of 413; 50.1%) or control group (206 of 413; 49.9%). The csPCa detection rate in the intervention group was higher, with an adjusted odds ratio of 1.79 (95% CI: 1.14, 2.79; P = .01). A subgroup of 89 men underwent RP (21.5%; 89 of 413). Multiparametric MRI helped correctly identify 131 of 182 csPCa foci in 89 men (sensitivity, 72%; 95% CI: 65, 78). The specificity, positive predictive value, and negative predictive value were 71% (91 of 128), 78% (131 of 168), and 64% (91 of 142), respectively. Conclusion Prebiopsy multiparametric MRI was accurate in the depiction of clinically significant PCa. Combining US and MRI fusion-targeted biopsies with systematic biopsies helped detect more clinically significant lesions than did systematic biopsies alone. Clinical trial registration no. NCT02745496 © RSNA, 2023 Supplemental material is available for this article.
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Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Idoso , Imageamento por Ressonância Magnética , Estudos Prospectivos , Biópsia Guiada por ImagemRESUMO
OBJECTIVES: The four nations of the United Kingdom (UK) have endorsed a new curriculum and credentialing process for consultant pharmacists. This study aimed to measure the self-reported consultant-level practice development needs of pharmacists across the UK. METHODS: The study was a cross-sectional electronic survey. Inclusion criteria were: pharmacists registered to practice with the General Pharmaceutical Council; working in any professional sector across the UK; and self-identifying as already working at an advanced level of practice or in an advanced pharmacist role. Participants were asked to rate their confidence that their current practice aligns to the level described in the Royal Pharmaceutical Society Consultant Pharmacist curriculum on a 5-point Likert scale. Predictors of overall confidence with the whole curriculum were analysed using binomial regression. KEY FINDINGS: Nine hundred and forty-four pharmacists participated. Median age was 42 years; 72.6% were female. Research skills and strategic leadership skills had low self-reported confidence. Patient-Centred Care and Collaboration was the domain with the highest reported confidence. 10.2% (96/944) of participants self-reported confidence across the whole curriculum. The strongest predictors of overall confidence across the curriculum were advanced clinical practitioner qualification, research qualifications and self-identifying as a specialist. Increasing age and male gender also predicted confidence. White ethnicity and having an independent prescribing qualification negatively predicted confidence. CONCLUSION: A small minority of pharmacists self-reported confidence across the whole curriculum. A planned approach to develop research skills across the career spectrum, coupled with better identification of workplace-based experiential strategic leadership opportunities, may help deliver a larger cohort of 'consultant-ready' pharmacists.
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Consultores , Farmacêuticos , Humanos , Masculino , Feminino , Adulto , Estudos Transversais , Reino Unido , AutorrelatoRESUMO
BACKGROUND: It is estimated that around 30% of breast cancers in post-menopausal women are related to lifestyle. The breast cancer-pooling project demonstrated that sustained weight loss of 2 to 4.5 kg is associated with an 18% lower risk of breast cancer, highlighting the importance of small changes in body weight. Our study aimed to assess the effectiveness a volunteer-delivered, community based, weight management programme (ActWELL) for women with a BMI > 25 kg/m2 attending NHS Scotland Breast Screening clinics. METHODS: A multicentre, 1:1 parallel group, randomised controlled trial was undertaken in 560 women aged 50 to 70 years with BMI > 25 kg/m2. On completion of baseline measures, all participants received a breast cancer prevention leaflet. Intervention group participants received the ActWELL intervention which focussed on personalised diet advice and pedometer walking plans. The programme was delivered in leisure centres by (the charity) Breast Cancer Now volunteer coaches. Primary outcomes were changes between groups at 12 months in body weight (kg) and physical activity (accelerometer measured step count). RESULTS: Two hundred seventy-nine women were allocated to the intervention group and 281 to the comparison group. Twelve-month data were available from 240 (81%) intervention and 227 (85%) comparison group participants. Coaches delivered 523 coaching sessions and 1915 support calls to 279 intervention participants. Mean weight change was - 2.5 kg (95% CI - 3.1 to - 1.9) in the intervention group and - 1.2 kg (- 1.8 to 0.6) in the comparison group. The adjusted mean difference was - 1.3 kg (95% CI - 2.2 to - 0.4, P = 0.003). The odds ratio for losing 5% weight was 2.20 (95% CI 1.4 to 3.4, p = 0.0005) in favour of the intervention. The adjusted mean difference in step counts between groups was 483 steps/day (95% CI - 635 to 1602) (NS). CONCLUSIONS: A community weight management intervention initiated at breast screening clinics and delivered by volunteer coaches doubled the likelihood of clinically significant weight loss at 12 months (compared with usual care) offering significant potential to decrease breast cancer risk. TRIAL REGISTRATION: Database of registration: ISCRTN. Registration number: 11057518 . Date trial registered:21.07.2017. Date of enrolment of first participant: 01.09.2017.
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Neoplasias da Mama/prevenção & controle , Redução de Peso , Acelerometria , Idoso , Neoplasias da Mama/diagnóstico , Serviços de Saúde Comunitária , Exercício Físico , Feminino , Humanos , Estilo de Vida , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Razão de Chances , Escócia , Voluntários , CaminhadaRESUMO
INTRODUCTION: Increased left ventricular mass index (LVMI) is associated with mortality in end-stage renal disease. LVMI regression may improve outcomes. Allopurinol has reduced LVMI in randomized controlled trials in chronic kidney disease, diabetes, and ischemic heart disease. This study investigated whether allopurinol would regress LVMI in hemodialysis patients. METHODS: This was a randomized placebo-controlled double-blind multicenter trial funded by the British Heart Foundation (PG/12/72/29743). A total of 80 patients undergoing regular maintenance hemodialysis were recruited from NHS Tayside, NHS Greater Glasgow and Clyde and NHS Ayrshire and Arran in Scotland, UK. Participants were randomly assigned on a 1:1 ratio to 12 months of therapy with allopurinol 300 mg or placebo after each dialysis session. The primary outcome was change in LVMI, as assessed by cardiac magnetic resonance imaging (CMRI) at baseline and 12 months. Secondary outcomes were change in BP, flow-mediated dilation (FMD), augmentation indices (AIx), and pulse wave velocity (PWV). RESULTS: A total of 53 patients, with a mean age of 58 years, completed the study and had CMRI follow-up data for analysis. Allopurinol did not regress LVMI (change in LVMI: placebo +3.6 ± 10.4 g/m2; allopurinol: +1.6 ± 11 g/m2; P = 0.49). Allopurinol had no demonstrable effect on BP, FMD, AIx, or PWV. CONCLUSION: Compared with placebo, treatment with allopurinol did not regress LVMI in this trial.
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INTRODUCTION: The A allele of rs1042713 (Arg16 amino acid) in the ß2-adrenoreceptor is associated with poor response to long-acting ß2-agonist (LABA) in young people with asthma. Our aim was to assess whether the prescribing of second-line controller with LABA or a leukotriene receptor antagonist according to Arg16Gly genotype would result in improvements in Pediatric Asthma-Related Quality of Life Questionnaire (PAQLQ). METHODS: We performed a pragmatic randomised controlled trial (RCT) via a primary care clinical research network covering England and Scotland. We enrolled participants aged 12-18â years with asthma taking inhaled corticosteroids. 241 participants (mean±sd age 14.7±1.91â years) were randomised (1:1) to receive personalised care (genotype directed prescribing) or standard guideline care. Following a 4-week run-in participants were followed for 12â months. The primary outcome measure was change in PAQLQ. Asthma control, asthma exacerbation frequency and healthcare utilisation were secondary outcomes. RESULTS: Genotype-directed prescribing resulted in an improvement in PAQLQ compared to standard care (0.16, 95% CI 0.00-0.31; p=0.049), although this improvement was below the pre-determined clinical threshold of 0.25. The AA genotype was associated with a larger improvement in PAQLQ with personalised versus standard care (0.42, 95% CI 0.02-0.81; p=0.041). CONCLUSION: This is the first RCT demonstrating that genotype-driven asthma prescribing is associated with a significant improvement in a clinical outcome compared to standard care. Adolescents with the AA homozygous genotype benefited most. The potential role of such ß2-adrenoceptor genotype directed therapy in younger and more severe childhood asthma warrants further exploration.
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Antiasmáticos , Asma , Administração por Inalação , Adolescente , Corticosteroides/uso terapêutico , Alelos , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/genética , Criança , Quimioterapia Combinada , Inglaterra , Genótipo , HumanosRESUMO
The EarlyCDT-Lung test is a high-specificity blood-based autoantibody biomarker that could contribute to predicting lung cancer risk. We report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent computed tomography (CT) scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/unspecified lung cancer at diagnosis compared with the standard clinical practice at the time the study began.The Early Diagnosis of Lung Cancer Scotland (ECLS) trial was a randomised controlled trial of 12â208 participants at risk of developing lung cancer in Scotland in the UK. The intervention arm received the EarlyCDT-Lung test and, if test-positive, low-dose CT scanning 6-monthly for up to 2â years. EarlyCDT-Lung test-negative and control arm participants received standard clinical care. Outcomes were assessed at 2â years post-randomisation using validated data on cancer occurrence, cancer staging, mortality and comorbidities.At 2â years, 127 lung cancers were detected in the study population (1.0%). In the intervention arm, 33 out of 56 (58.9%) lung cancers were diagnosed at stage III/IV compared with 52 out of 71 (73.2%) in the control arm. The hazard ratio for stage III/IV presentation was 0.64 (95% CI 0.41-0.99). There were nonsignificant differences in lung cancer and all-cause mortality after 2â years.ECLS compared EarlyCDT-Lung plus CT screening to standard clinical care (symptomatic presentation) and was not designed to assess the incremental contribution of the EarlyCDT-Lung test. The observation of a stage shift towards earlier-stage lung cancer diagnosis merits further investigations to evaluate whether the EarlyCDT-Lung test adds anything to the emerging standard of low-dose CT.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Testes Hematológicos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Escócia/epidemiologiaRESUMO
BACKGROUND: Advanced chronic kidney disease is common in older people and is frequently accompanied by metabolic acidosis. Oral sodium bicarbonate is used to treat this acidosis, but evidence is lacking on whether or not this provides a net gain in health or quality of life for older people. OBJECTIVES: The objectives were to determine whether or not oral bicarbonate therapy improves physical function, quality of life, markers of renal function, bone turnover and vascular health compared with placebo in older people with chronic kidney disease and mild acidosis; to assess the safety of oral bicarbonate; and to establish whether or not oral bicarbonate therapy is cost-effective in this setting. DESIGN: A parallel-group, double-blind, placebo-controlled randomised trial. SETTING: The setting was nephrology and geriatric medicine outpatient departments in 27 UK hospitals. PARTICIPANTS: Participants were adults aged ≥ 60 years with advanced chronic kidney disease (glomerular filtration rate category 4 or 5, not on dialysis) with a serum bicarbonate concentration of < 22 mmol/l. INTERVENTIONS: Eligible participants were randomised 1 : 1 to oral sodium bicarbonate or matching placebo. Dosing started at 500 mg three times daily, increasing to 1 g three times daily if the serum bicarbonate concentration was < 22 mmol/l at 3 months. MAIN OUTCOME MEASURES: The primary outcome was the between-group difference in the Short Physical Performance Battery score at 12 months, adjusted for baseline. Other outcome measures included generic and disease-specific health-related quality of life, anthropometry, 6-minute walk speed, grip strength, renal function, markers of bone turnover, blood pressure and brain natriuretic peptide. All adverse events were recorded, including commencement of renal replacement therapy. For the health economic analysis, the incremental cost per quality-adjusted life-year was the main outcome. RESULTS: In total, 300 participants were randomised, 152 to bicarbonate and 148 to placebo. The mean age of participants was 74 years and 86 (29%) were female. Adherence to study medication was 73% in both groups. A total of 220 (73%) participants were assessed at the 12-month visit. No significant treatment effect was evident for the primary outcome of the between-group difference in the Short Physical Performance Battery score at 12 months (-0.4 points, 95% confidence interval -0.9 to 0.1 points; p = 0.15). No significant treatment benefit was seen for any of the secondary outcomes. Adverse events were more frequent in the bicarbonate arm (457 vs. 400). Time to commencement of renal replacement therapy was similar in both groups (hazard ratio 1.22, 95% confidence interval 0.74 to 2.02; p = 0.43). Health economic analysis showed higher costs and lower quality of life in the bicarbonate arm at 1 year, with additional costs of £564 (95% confidence interval £88 to £1154) and a quality-adjusted life-year difference of -0.05 (95% confidence interval -0.08 to -0.01); placebo dominated bicarbonate under all sensitivity analyses for incremental cost-effectiveness. LIMITATIONS: The trial population was predominantly white and male, limiting generalisability. The increment in serum bicarbonate concentrations achieved was small and a benefit from larger doses of bicarbonate cannot be excluded. CONCLUSIONS: Oral sodium bicarbonate did not improve a range of health measures in people aged ≥ 60 years with chronic kidney disease category 4 or 5 and mild acidosis, and is unlikely to be cost-effective for use in the NHS in this patient group. Once other current trials of bicarbonate therapy in chronic kidney disease are complete, an individual participant meta-analysis would be helpful to determine which subgroups, if any, are more likely to benefit and which treatment regimens are more beneficial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN09486651 and EudraCT 2011-005271-16. The systematic review is registered as PROSPERO CRD42018112908. 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. 24, No. 27. See the NIHR Journals Library website for further project information.
Patients with advanced chronic kidney disease often have excessive levels of acid in their blood (acidosis). Acidosis has been associated with a range of other problems that particularly affect patients with chronic kidney disease, including weaker muscles, weaker bones, worse blood vessel health and kidney disease that worsens more quickly. For decades, acidosis has been treated with sodium bicarbonate tablets (the ingredient found in baking soda) to neutralise the excess acid. However, sodium bicarbonate is awkward to take, may cause side effects and may increase blood pressure. To clarify whether or not sodium bicarbonate caused an overall improvement in health, we carried out a study involving 300 people aged ≥ 60 years with advanced chronic kidney disease and mild acidosis. Half received sodium bicarbonate capsules and half received dummy capsules (placebo), for up to 2 years. The treatments were chosen randomly by a computer and the participants, their doctors and the researchers were not aware of the treatment received until the end of the study. We measured physical function (walking speed, ability to stand from a chair, balance) alongside quality of life, kidney function, bone and blood vessel health, side effects and health service use over 2 years. We found that sodium bicarbonate did not improve physical function or quality of life compared with placebo. Sodium bicarbonate also did not improve kidney function, bone health or blood vessel health compared with placebo. More people in the sodium bicarbonate group than in the placebo group had side effects, although blood pressure was the same in both groups. Health-care costs were higher in the sodium bicarbonate group than in the placebo group. We conclude that oral sodium bicarbonate did not significantly improve health measures compared with placebo for older people (aged ≥ 60 years) with advanced chronic kidney disease associated with mild acidosis.
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Biomarcadores/sangue , Exercício Físico , Qualidade de Vida/psicologia , Insuficiência Renal Crônica/tratamento farmacológico , Bicarbonato de Sódio/administração & dosagem , Idoso , Análise Custo-Benefício , Método Duplo-Cego , Feminino , Humanos , Masculino , Reino UnidoRESUMO
PURPOSE: The STAKT study examined short-term exposure (4.5 days) to the oral selective pan-AKT inhibitor capivasertib (AZD5363) to determine if this drug can reach its therapeutic target in sufficient concentration to significantly modulate key biomarkers of the AKT pathway and tumor proliferation. PATIENTS AND METHODS: STAKT was a two-stage, double-blind, randomized, placebo-controlled, "window-of-opportunity" study in patients with newly diagnosed ER+ invasive breast cancer. Stage 1 assessed capivasertib 480 mg b.i.d. (recommended monotherapy dose) and placebo, and stage 2 assessed capivasertib 360 and 240 mg b.i.d. Primary endpoints were changes from baseline in AKT pathway markers pPRAS40, pGSK3ß, and proliferation protein Ki67. Pharmacologic and pharmacodynamic properties were analyzed from blood sampling, and tolerability by adverse-event monitoring. RESULTS: After 4.5 days' exposure, capivasertib 480 mg b.i.d. (n = 17) produced significant decreases from baseline versus placebo (n = 11) in pGSK3ß (H-score absolute change: -55.3, P = 0.006) and pPRAS40 (-83.8, P < 0.0001), and a decrease in Ki67 (absolute change in percentage positive nuclei: -9.6%, P = 0.031). Significant changes also occurred in secondary signaling biomarker pS6 (-42.3, P = 0.004), while pAKT (and nuclear FOXO3a) also increased in accordance with capivasertib's mechanism (pAKT: 81.3, P = 0.005). At doses of 360 mg b.i.d. (n = 5) and 240 mg b.i.d. (n = 6), changes in primary and secondary biomarkers were also observed, albeit of smaller magnitude. Biomarker modulation was dose and concentration dependent, and no new safety signals were evident. CONCLUSIONS: Capivasertib 480 mg b.i.d. rapidly modulates key biomarkers of the AKT pathway and decreases proliferation marker Ki67, suggesting future potential as an effective therapy in AKT-dependent breast cancers.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Receptor alfa de Estrogênio/metabolismo , Antígeno Ki-67/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Pirimidinas/farmacocinética , Pirimidinas/uso terapêutico , Pirróis/farmacocinética , Pirróis/uso terapêutico , Neoplasias da Mama/patologia , Proliferação de Células , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Distribuição Tecidual , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to explore the feasibility of conducting a randomized controlled trial of dynamic Lycra® orthoses as an adjunct to arm rehabilitation after stroke and to explore the magnitude and direction of change on arm outcomes. DESIGN: This is a single-blind, two-arm parallel group, feasibility randomized controlled trial. SETTING: In-patient rehabilitation. SUBJECTS: The study participants were stroke survivors with arm hemiparesis two to four weeks after stroke receiving in-patient rehabilitation. INTERVENTIONS: Participants were randomized 2:1 to wear Lycra® gauntlets for eight hours daily for eight weeks, plus usual rehabilitation (n = 27), or to usual rehabilitation only (n = 16). MAIN MEASURES: Recruitment, retention, fidelity, adverse events and completeness of data collection were examined at 8 and 16 weeks; arm function (activity limitation; Action Research Arm Test, Motor Activity Log) and impairment (Nine-hole Peg Test, Motricity Index, Modified Tardieu Scale). Structured interviews explored acceptability. RESULTS: Of the target of 51, 43 (84%) participants were recruited. Retention at 8 weeks was 32 (79%) and 24 (56%) at 16 weeks. In total, 11 (52%) intervention group participants and 6 (50%) control group participants (odds ratio = 1.3, 95% confidence interval = 0.2 to 7.8) had improved Action Research Arm Test level by 8 weeks; at 16 weeks, this was 8 (61%) intervention and 6 (75.0%) control participants (odds ratio = 1.1, 95% confidence interval = 0.1 to 13.1). Change on other measures favoured control participants. Acceptability was influenced by 26 adverse reactions. CONCLUSION: Recruitment and retention were low, and adverse reactions were problematic. There were no indications of clinically relevant effects, but the small sample means definitive conclusions cannot be made. A definitive trial is not warranted without orthoses adaptation.
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Aparelhos Ortopédicos , Paresia/reabilitação , Reabilitação do Acidente Vascular Cerebral , Extremidade Superior/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paresia/fisiopatologia , Método Simples-Cego , Acidente Vascular Cerebral/fisiopatologia , Adulto JovemRESUMO
INTRODUCTION: In Scotland, the incidence of breast cancer is predicted to rise significantly in the next few decades and while there are measures to support reductions in morbidity and mortality, the breast cancer community is currently exploring preventative opportunities including supporting weight management programmes in postmenopausal women. This study aims to assess the effectiveness and cost-effectiveness of a theory-based, community delivered, minimal contact, weight management (diet, physical activity and behaviour change techniques) programme (ActWELL) in women with a body mass index (BMI) >25 kg/m2 attending routine breast cancer screening appointments. METHODS AND ANALYSIS: The study will be a four-centre, 1:1 parallel group randomised controlled trial of a 12-month weight management intervention initiated in breast cancer screening centres, delivered by trained Breast Cancer Now lifestyle coaches in community settings. The intervention programme involves two intervention meetings with coaches plus (up to) nine telephone contacts over 12 months. The programme will focus on personalised diet (including alcoholic and sugary drinks) and physical activity habits. Behaviour change techniques include self-monitoring, goal setting, implementation intentions, action and coping plans. The study has a sample size of 414 women with a BMI >25 kg/m2 attending routine National Health Service breast cancer screening appointments. Measures will be taken at baseline, 12 weeks and at 12-month follow-up, complemented by qualitative interviews exploring perceived acceptability and impact on habitual behaviours. The two co-primary outcomes are mean change in measured body weight and change in physical activity between groups to 12 months. Secondary outcomes are changes in eating habits, alcohol intake, sedentary time, quality of life, waist circumference, lipid, haemoglobin A1c and insulin profiles, blood pressure and cost-effectiveness of the intervention. ETHICS AND DISSEMINATION: The protocol has been approved by East of Scotland Research Ethics Committee (17/ES/0073). All participants provide written informed consent. Dissemination will be through peer-reviewed publication and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN11057518; Pre-results.
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Neoplasias da Mama/prevenção & controle , Atenção à Saúde/organização & administração , Estilo de Vida , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Dieta , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Qualidade de VidaRESUMO
BACKGROUND: Between 50% and 80% of people with multiple sclerosis (PwMS) experience neurogenic bowel dysfunction (NBD) (i.e. constipation and faecal incontinence) that affects quality of life and can lead to hospitalisation. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of abdominal massage plus advice on bowel symptoms on PwMS compared with advice only. A process evaluation investigated the factors that affected the clinical effectiveness and possible implementation of the different treatments. DESIGN: A randomised controlled trial with process evaluation and health economic components. Outcome analysis was undertaken blind. SETTING: The trial took place in 12 UK hospitals. PARTICIPANTS: PwMS who had 'bothersome' NBD. INTERVENTION: Following individualised training, abdominal massage was undertaken daily for 6 weeks (intervention group). Advice on good bowel management as per the Multiple Sclerosis Society advice booklet was provided to both groups. All participants received weekly telephone calls from the research nurse. MAIN OUTCOME MEASURES: The primary outcome was the difference between the intervention and control groups in change in the NBD score from baseline to week 24. Secondary outcomes were measured via a bowel diary, adherence diary, the Constipation Scoring System, patient resource questionnaire and the EuroQol-5 Dimensions, five-level version (EQ-5D-5L). RESULTS: A total of 191 participants were finalised, 189 of whom were randomised (two participants were finalised in error) (control group, n = 99; intervention group, n = 90) and an intention-to-treat analysis was performed. The mean age was 52 years (standard deviation 10.83 years), 81% (n = 154) were female and 11% (n = 21) were wheelchair dependent. Fifteen participants from the intervention group and five from the control group were lost to follow-up. The change in NBD score by week 24 demonstrated no significant difference between groups [mean difference total score -1.64, 95% confidence interval (CI) -3.32 to 0.04; p = 0.0558]; there was a significant difference between groups in the change in the frequency of stool evacuation per week (mean difference 0.62, 95% CI 0.03 to 1.21; p = 0.039) and in the number of times per week that participants felt that they emptied their bowels completely (mean difference 1.08, 95% CI 0.41 to 1.76; p = 0.002), in favour of the intervention group. Of participant interviewees, 75% reported benefits, for example less difficulty passing stool, more complete evacuations, less bloated, improved appetite, and 85% continued with the massage. A cost-utility analysis conducted from a NHS and patient cost perspective found in the imputed sample with bootstrapping a mean incremental outcome effect of the intervention relative to usual care of -0.002 quality-adjusted life-years (QALYs) (95% CI -0.029 to 0.027 QALYs). In the same imputed sample with bootstrapping, the mean incremental cost effect of the intervention relative to usual care was £56.50 (95% CI -£372.62 to £415.68). No adverse events were reported. Limitations include unequal randomisation, dropout and the possibility of ineffective massage technique. CONCLUSION: The increment in the primary outcome favoured the intervention group, but it was small and not statistically significant. The economic analysis identified that the intervention was dominated by the control group. Given the small improvement in the primary outcome, but not in terms of QALYs, a low-cost version of the intervention might be considered worthwhile by some patients. FUTURE WORK: Research is required to establish possible mechanisms of action and modes of massage delivery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN85007023 and NCT03166007. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 58. See the NIHR Journals Library website for further project information.
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Massagem/economia , Massagem/métodos , Esclerose Múltipla/complicações , Intestino Neurogênico/etiologia , Intestino Neurogênico/terapia , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , Análise Custo-Benefício , Feminino , Gastos em Saúde , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/economia , Educação de Pacientes como Assunto/métodos , Qualidade de Vida , Fatores Sexuais , Método Simples-CegoRESUMO
OBJECTIVES: To determine the psychological response (thoughts, perceptions and affect) to a diagnosis of pulmonary nodules following a novel antibody blood test and computed tomography (CT) scans within a UK population. MATERIALS AND METHODS: This study was nested within a randomised controlled trial of a blood test (Early CDT®-Lung test), followed by a chest x-ray and serial CT-scanning of those with a positive blood test for early detection of lung cancer (ECLS Study). Trial participants with a positive Early CDT®-Lung test were invited to participate (n = 338) and those agreeing completed questionnaires assessing psychological outcomes at 1, 3 and 6 months following trial recruitment. Responses of individuals with pulmonary nodules on their first CT scan were compared to those without (classified as normal CT) at 3 and 6 months follow-up using random effects regression models to account for multiple observations per participant, with loge transformation of data where modelling assumptions were not met. RESULTS: There were no statistically significant differences between the nodule and normal CT groups in affect, lung cancer worry, health anxiety, illness perceptions, lung cancer risk perception or intrusive thoughts at 3 or 6 months post-recruitment. The nodule group had statistically significantly fewer avoidance symptoms compared to the normal CT group at 3 months (impact of events scale avoidance (IES-A) difference between means -1.99, 95%CI -4.18, 0.21) than at 6 months (IES-A difference between means 0.88, 95%CI -1.32, 3.08; p-value for change over time = 0.003) with similar findings using loge transformed data. CONCLUSION: A diagnosis of pulmonary nodules following an Early CDT®-Lung test and CT scan did not appear to result in adverse psychological responses compared to those with a normal CT scan.
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Testes Hematológicos/métodos , Neoplasias Pulmonares/psicologia , Nódulos Pulmonares Múltiplos/psicologia , Tomografia Computadorizada por Raios X/métodos , Idoso , Aprendizagem da Esquiva , Estudos de Casos e Controles , Detecção Precoce de Câncer , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico , Percepção , Inquéritos e Questionários , Pensamento , Reino UnidoRESUMO
Design: double-blind, parallel group, placebo-controlled randomised trial. Methods: we recruited people aged >65 years with at least one fall in the previous year. Participants received 4 mg perindopril or placebo daily for 15 weeks. The primary outcome was the between-group difference in force-plate measured anteroposterior (AP) sway at 15 weeks. Secondary outcomes included other measures of postural sway, limits of stability during maximal forward, right and left leaning, blood pressure, muscle strength, 6-min walk distance and falls. The primary outcome was assessed using two-way ANOVA, adjusted for baseline factors. Results: we randomised 80 participants. Mean age was 78.0 (SD 7.4) years; 60 (75%) were female. About 77/80 (96%) completed the trial. At 15 weeks there were no significant between-group differences in AP sway with eyes open (mean difference 0 mm, 95% CI -8 to 7 mm, P = 0.91) or eyes closed (mean difference 2 mm, 95% CI -7 to 12 mm, P = 0.59); no differences in other measures of postural stability, muscle strength or function. About 16/40 (42%) of patients in each group had orthostatic hypotension at follow-up. The median number (IQR) of falls was 1 (0,4) in the perindopril versus 1 (0,2) in the placebo group (P = 0.24). Conclusions: perindopril did not improve postural sway in older people at risk of falls. Clinical Trials Registration: ISRCTN58995463.
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Acidentes por Quedas/prevenção & controle , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Perindopril/uso terapêutico , Equilíbrio Postural/efeitos dos fármacos , Transtornos de Sensação/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Método Duplo-Cego , Feminino , Avaliação Geriátrica , Humanos , Masculino , Perindopril/efeitos adversos , Fatores de Risco , Escócia , Transtornos de Sensação/complicações , Transtornos de Sensação/diagnóstico , Transtornos de Sensação/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Despite being a core component of self-management, goal setting is rarely used in routine care. We piloted a primary care, nurse-led intervention called Achieving Good Outcomes for Asthma Living (GOAL) for adults with asthma. Patients were invited to identify and prioritise their goals in preparation for discussing and negotiating an action/coping plan with the nurse at a routine asthma review. METHODS: The 18-month mixed methods feasibility cluster pilot trial stratified and then randomised practices to deliver usual care (UC) or a goal-setting intervention (GOAL). Practice asthma nurses and adult patients with active asthma were invited to participate. The primary outcome was asthma-specific quality of life. Semi-structured interviews with a purposive patient sample (n = 14) and 10 participating nurses explored GOAL perception. The constructs of normalisation process theory (NPT) were used to analyse and interpret data. RESULTS: Ten practices participated (five in each arm), exceeding our target of eight. However, only 48 patients (target 80) were recruited (18 in GOAL practices). At 6 months post-intervention, the difference in mean asthma-related quality of life (mAQLQ) between intervention and control was 0.1 (GOAL 6.20: SD 0.76 (CI 5.76-6.65) versus UC 6.1: SD 0.81 (CI 5.63-6.57)), less than the minimal clinically important difference (MCID) of 0.5. However, change from baseline was stronger in the intervention group: at 6 months the change in the emotions sub-score was 0.8 for intervention versus 0.2 for control. Costs were higher in the intervention group by £22.17. Routine review with goal setting was considered more holistic, enhancing rapport and enabling patients to become active rather than passive participants in healthcare. However, time was a major barrier for nurses, who admitted to screening out patient goals they believed were unrelated to asthma. CONCLUSIONS: The difference in AQLQ score from baseline is larger in the intervention arm than the control, indicating the intervention may have impact if appropriately strengthened. The GOAL intervention changed the review dynamic and was well received by patients, but necessitated additional time, which was problematic in the confines of the traditional nurse appointment. Modification to recruitment methods and further development of the intervention are needed before proceeding to a definitive cluster randomised controlled trial. TRIAL REGISTRATION: ISRCTN18912042 . Registered on 26 June 2012.
Assuntos
Asma/enfermagem , Comunicação , Planejamento de Assistência ao Paciente , Relações Médico-Enfermeiro , Enfermagem de Atenção Primária , Atenção Primária à Saúde , Qualidade de Vida , Autocuidado , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/diagnóstico , Asma/fisiopatologia , Asma/psicologia , Atitude do Pessoal de Saúde , Efeitos Psicossociais da Doença , Estudos de Viabilidade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Participação do Paciente , Projetos Piloto , Pesquisa Qualitativa , Escócia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are linked to prostate cancer, but their effect on biochemical recurrence (BR) remains unknown. Our aims were to investigate the incidence and risk of BR in men on ACEIs/ARBs after radical radiotherapy with adjuvant∖neoadjuvant hormone treatment. MATERIAL AND METHODS: A propensity score analysis of 558 men was conducted. Men were stratified into 3 groups: hypertensive men on ACEIs/ARBs (as a study group), non-hypertensive men not on ACEIs/ARBs, and hypertensive men not on ACEIs/ARBs (both as a control group). The multivariate analysis of variance, chi-square, Kruskal-Wallis, analysis of variance, risk ratio, confidence interval, Kaplan-Meier plots, and log-rank tests were used. RESULTS: The mean age and follow-up were 68.51 and 3.33 years, respectively. There was a statistically significant difference in the prevalence of BR among the treatment groups (P < .001). The incidence of BR was significantly lower in hypertensive men taking ACEIs/ARBs than in non-hypertensive men not taking ACEIs/ARBs (P < .001) or in hypertensive men not taking ACEIs/ARBs (P < .009). The incidence of BR was significantly lower in hypertensive men not taking ACEIs/ARBs than in non-hypertensive men not taking ACEIs/ARBs (P < .013). The risk ratio (RR) of BR in the group of hypertensive men taking ACEIs/ARBs was significantly lower than in the group of non-hypertensive men not taking ACEIs/ARBs (RR, 0.74; 95% CI, 0.64-0.86; P < .001) and in the group of hypertensive men not taking ACEIs/ARBs (RR, 0.78; 95% CI, 0.67-0.91; P < .001). The time-to-event analysis revealed that the group of hypertensive men taking ACEIs/ARBs was significantly different compared with the control groups (P < .031). CONCLUSION: Men who were taking ACEIs/ARBs had significantly lower incidence of BR after radical radiotherapy with hormone treatment. The intake of ACEIs/ARBs was associated with reduced risk of BR.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hipertensão/tratamento farmacológico , Calicreínas/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Pontuação de Propensão , Neoplasias da Próstata/metabolismo , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To determine whether spironolactone could benefit older people with osteoarthritis (OA), based on a previous study showing that spironolactone improved quality of life. METHODS: This parallel-group, randomized, placebo-controlled, double-blind trial randomized community-dwelling people ages ≥70 years with symptomatic knee OA to 12 weeks of 25 mg daily oral spironolactone or matching placebo. The primary outcome was between-group difference in change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores. Secondary outcomes included WOMAC stiffness and physical function subscores, EuroQol 5-domain (EQ-5D) 3L score, and mechanistic markers. Analysis was by intent to treat, using mixed-model regression, adjusting for baseline values of test variables. RESULTS: A total of 421 people had eligibility assessed, and 86 were randomized. Mean ± SD age was 77 ± 5 years and 53 of 86 (62%) were women. Adherence to study medication was 99%, and all participants completed the 12-week assessment. No significant improvement was seen in the WOMAC pain score (adjusted treatment effect 0.5 points [95% confidence interval (95% CI) - 0.3, 1.3]; P = 0.19). No improvement was seen in WOMAC stiffness score (0.2 points [95% CI -0.6, 1.1]; P = 0.58), WOMAC physical function score (0.0 points [95% CI -0.7, 0.8]; P = 0.98), or EQ-5D 3L score (0.04 points [95% CI -0.04, 0.12]; P = 0.34). Cortisol, matrix metalloproteinase 3, and urinary C-telopeptide of type II collagen were not significantly different between groups. More minor adverse events were noted in the spironolactone group (47 versus 32), but no increase in death or hospitalization was evident. CONCLUSION: Spironolactone did not improve symptoms, physical function, or health-related quality of life in older people with knee OA.
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Artralgia/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Espironolactona/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Artralgia/etiologia , Artralgia/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Análise de Intenção de Tratamento , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/fisiopatologia , Masculino , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/fisiopatologia , Medição da Dor , Análise de Regressão , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
PURPOSE: To determine whether participants taking angiotensin-converting enzyme inhibitors (ACEIs) and treated with radical radiation therapy with neoadjuvant/adjuvant hormone therapy have less incidence, severity, and duration of radiation proctitis. METHODS AND MATERIALS: A propensity score analysis of 817 patients who underwent radical radiation therapy with neoadjuvant or adjuvant hormone therapy as primary line management in a cohort study during 2009 to 2013 was conducted. Patients were stratified as follows: group 1, hypertensive patients taking ACEIs (as a study group); group 2, nonhypertensive patients not taking ACEIs; and group 3, hypertensive patients not taking ACEIs (both as control groups). The incidence, severity, and duration of proctitis were the main outcome. χ(2) tests, Mann-Whitney U tests, analysis of variance, risk ratio (RR), confidence interval (CI), Kaplan-Meier plots, and log-rank tests were used. RESULTS: The mean age of the participants was 68.91 years, with a follow-up time of 3.38 years. Based on disease and age-matched comparison, there was a statistically significant difference of proctitis grading between the 3 groups: χ(2) (8, n=308) = 72.52, P<.001. The Mann-Whitney U test indicated that grades of proctitis were significantly lower in hypertensive patients taking ACEIs than in nonhypertensive patients not taking ACEIs and hypertensive patients not taking ACEIs (P<.001). The risk ratio (RR) of proctitis in hypertensive patients taking ACEIs was significantly lower than in hypertensive patients not taking ACEIs (RR 0.40, 95% CI 0.30-0.53, P<.001) and in nonhypertensive patients not taking ACEIs (RR 0.58, 95% CI 0.44-0.77, P<.001). Time to event analysis revealed that hypertensive patients taking ACEIs were significantly different from the control groups (P<.0001). Furthermore, hypertensive patients taking ACEIs had significantly faster resolution of proctitis (P<.0001). CONCLUSION: Patients who were taking ACEIs were significantly less likely to have high-grade proctitis after radical radiation therapy with neoadjuvant or adjuvant hormone therapy (P<.001). The intake of ACEIs was significantly associated with a reduced risk of radiation-induced proctitis and also with acceleration of its resolution.