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BACKGROUND: Treatments for osteoarthritis (OA) are limited. Previous small studies suggest that the antirheumatic drug methotrexate may be a potential treatment for OA pain. OBJECTIVE: To assess symptomatic benefits of methotrexate in knee OA (KOA). DESIGN: A multicenter, randomized, double-blind, placebo-controlled trial done between 13 June 2014 and 13 October 2017. (ISRCTN77854383; EudraCT: 2013-001689-41). SETTING: 15 secondary care musculoskeletal clinics in the United Kingdom. PARTICIPANTS: A total of 207 participants with symptomatic, radiographic KOA and knee pain (severity ≥4 out of 10) on most days in the past 3 months with inadequate response to current medication were approached for inclusion. INTERVENTION: Participants were randomly assigned 1:1 to oral methotrexate once weekly (6-week escalation 10 to 25 mg) or matched placebo over 12 months and continued usual analgesia. MEASUREMENTS: The primary end point was average knee pain (numerical rating scale [NRS] 0 to 10) at 6 months, with 12-month follow-up to assess longer-term response. Secondary end points included knee stiffness and function outcomes and adverse events (AEs). RESULTS: A total of 155 participants (64% women; mean age, 60.9 years; 50% Kellgren-Lawrence grade 3 to 4) were randomly assigned to methotrexate (n = 77) or placebo (n = 78). Follow-up was 86% (n = 134; methotrexate: 66, placebo: 68) at 6 months. Mean knee pain decreased from 6.4 (SD, 1.80) at baseline to 5.1 (SD, 2.32) at 6 months in the methotrexate group and from 6.8 (SD, 1.62) to 6.2 (SD, 2.30) in the placebo group. The primary intention-to-treat analysis showed a statistically significant pain reduction of 0.79 NRS points in favor of methotrexate (95% CI, 0.08 to 1.51; P = 0.030). There were also statistically significant treatment group differences in favor of methotrexate at 6 months for Western Ontario and McMaster Universities Osteoarthritis Index stiffness (0.60 points [CI, 0.01 to 1.18]; P = 0.045) and function (5.01 points [CI, 1.29 to 8.74]; P = 0.008). Treatment adherence analysis supported a dose-response effect. Four unrelated serious AEs were reported (methotrexate: 2, placebo: 2). LIMITATION: Not permitting oral methotrexate to be changed to subcutaneous delivery for intolerance. CONCLUSION: Oral methotrexate added to usual medications demonstrated statistically significant reduction in KOA pain, stiffness, and function at 6 months. PRIMARY FUNDING SOURCE: Versus Arthritis.
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BACKGROUND: People need high-quality information to make decisions about research participation. Providing information in written format alone is conventional but may not be the most effective and acceptable approach. We developed a structure for the presentation of information using multimedia which included generic and trial-specific content. Our aim was to embed 'Studies Within A Trial' (SWATs) across multiple ongoing trials to test whether multimedia presentation of patient information led to better rates of recruitment. METHODS: Five trials included a SWAT and randomised their participants to receive a multimedia presentation alongside standard information, or standard written information alone. We collected data on trial recruitment, acceptance and retention and analysed the pooled results using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised following an invitation to take part. RESULTS: Five SWATs provided data on the primary outcome of proportion of participants randomised. Multimedia alongside written information results in little or no difference in recruitment rates (pooled odds ratio = 0.96, 95% CI: 0.79 to 1.17, p-value = 0.671, I2 = 0%). There was no effect on any other outcomes. CONCLUSIONS: Multimedia alongside written information did not improve trial recruitment rates. TRIAL REGISTRATION: ISRCTN71952900, ISRCTN 06710391, ISRCTN 17160087, ISRCTN05926847, ISRCTN62869767.
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Multimídia , Projetos de Pesquisa , Humanos , Seleção de Pacientes , Razão de ChancesRESUMO
AIM: Pragmatic clinical trials (PCTs) are randomized trials implemented through routine clinical practice, where design parameters of traditional randomized controlled trials are modified to increase generalizability. However, this may introduce statistical challenges. We aimed to identify these challenges and discuss possible solutions leading to best practice recommendations for the design and analysis of PCTs. METHODS: A modified Delphi method was used to reach consensus among a panel of 11 experts in clinical trials and statistics. Statistical issues were identified in a focused literature review and aggregated with insights and possible solutions from experts collected through a series of survey iterations. Issues were ranked according to their importance. RESULTS: Twenty-seven articles were included and combined with experts' insight to generate a list of issues categorized into participants, recruiting sites, randomization, blinding and intervention, outcome (selection and measurement) and data analysis. Consensus was reached about the most important issues: risk of participants' attrition, heterogeneity of "usual care" across sites, absence of blinding, use of a subjective endpoint and data analysis aligned with the trial estimand. Potential issues should be anticipated and preferably be addressed in the trial protocol. The experts provided solutions regarding data collection and data analysis, which were considered of equal importance. DISCUSSION: A set of important statistical issues in PCTs was identified and approaches were suggested to anticipate and/or minimize these through data analysis. Any impact of choosing a pragmatic design feature should be gauged in the light of the trial estimand.
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Projetos de Pesquisa , Humanos , ConsensoRESUMO
OBJECTIVES: To explore any age-related trend in workplace slip rate and assess the effectiveness of appropriate slip-resistant footwear in preventing workplace slips by age. METHODS: Secondary data analysis of the Stopping Slips among Healthcare Workers trial, a two-arm randomised controlled trial conducted between March 2017 and May 2019. 4553 National Health Service (NHS) staff across seven sites in England were randomised 1:1 to the intervention group (provision of 5* GRIP-rated slip-resistant footwear) or the control group (usual work footwear). The primary outcome was self-reported workplace slips, ascertained primarily through weekly text messages throughout the 14-week trial follow-up and analysed using mixed-effects negative binomial regression. This paper reports a control group-only analysis of the association between age and slip rate, and a full intention-to-treat analysis of the effectiveness of slip-resistant footwear by age. RESULTS: The mean age of participants was 43 years (range 18-74). In the control group-only analysis, slip rate differed by age (p<0.001) with those aged 60+ having double the slip rate of those aged <30 years (95% CI 1.40 to 2.87). In the intention-to-treat analysis, the interaction between allocation and age was statistically significant (p=0.002). In addition, for all age groups except those aged <30 years, the slip rate in the intervention group was statistically significantly lower than the control group; the smallest incidence rate ratio (ie, the biggest effect) was 0.39 (95% CI 0.24 to 0.64) in the 60+ age group. CONCLUSION: The provision of appropriate slip-resistant footwear was more effective at reducing workplace slips for older NHS staff.
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Sapatos , Local de Trabalho , Adolescente , Adulto , Idoso , Pessoal de Saúde , Humanos , Lactente , Pessoa de Meia-Idade , Medicina Estatal , Adulto JovemRESUMO
BACKGROUND: Manipulation under anaesthesia and arthroscopic capsular release are costly and invasive treatments for frozen shoulder, but their effectiveness remains uncertain. We compared these two surgical interventions with early structured physiotherapy plus steroid injection. METHODS: In this multicentre, pragmatic, three-arm, superiority randomised trial, patients referred to secondary care for treatment of primary frozen shoulder were recruited from 35 hospital sites in the UK. Participants were adults (≥18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation (≥50%) in the affected shoulder. Participants were randomly assigned (2:2:1) to receive manipulation under anaesthesia, arthroscopic capsular release, or early structured physiotherapy. In manipulation under anaesthesia, the surgeon manipulated the affected shoulder to stretch and tear the tight capsule while the participant was under general anaesthesia, supplemented by a steroid injection. Arthroscopic capsular release, also done under general anaesthesia, involved surgically dividing the contracted anterior capsule in the rotator interval, followed by manipulation, with optional steroid injection. Both forms of surgery were followed by postprocedural physiotherapy. Early structured physiotherapy involved mobilisation techniques and a graduated home exercise programme supplemented by a steroid injection. Both early structured physiotherapy and postprocedural physiotherapy involved 12 sessions during up to 12 weeks. The primary outcome was the Oxford Shoulder Score (OSS; 0-48) at 12 months after randomisation, analysed by initial randomisation group. We sought a target difference of 5 OSS points between physiotherapy and either form of surgery, or 4 points between manipulation and capsular release. The trial registration is ISRCTN48804508. FINDINGS: Between April 1, 2015, and Dec 31, 2017, we screened 914 patients, of whom 503 (55%) were randomly assigned. At 12 months, OSS data were available for 189 (94%) of 201 participants assigned to manipulation (mean estimate 38·3 points, 95% CI 36·9 to 39·7), 191 (94%) of 203 participants assigned to capsular release (40·3 points, 38·9 to 41·7), and 93 (94%) of 99 participants assigned to physiotherapy (37·2 points, 35·3 to 39·2). The mean group differences were 2·01 points (0·10 to 3·91) between the capsular release and manipulation groups, 3·06 points (0·71 to 5·41) between capsular release and physiotherapy, and 1·05 points (-1·28 to 3·39) between manipulation and physiotherapy. Eight serious adverse events were reported with capsular release and two with manipulation. At a willingness-to-pay threshold of £20â000 per quality-adjusted life-year, manipulation under anaesthesia had the highest probability of being cost-effective (0·8632, compared with 0·1366 for physiotherapy and 0·0002 for capsular release). INTERPRETATION: All mean differences on the assessment of shoulder pain and function (OSS) at the primary endpoint of 12 months were less than the target differences. Therefore, none of the three interventions were clinically superior. Arthoscopic capsular release carried higher risks, and manipulation under anaesthesia was the most cost-effective. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
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Bursite/terapia , Glucocorticoides/administração & dosagem , Liberação da Cápsula Articular , Manipulação Ortopédica , Modalidades de Fisioterapia , Atenção Secundária à Saúde , Adulto , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Resultado do Tratamento , Reino UnidoRESUMO
BACKGROUND: Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. The use of immediate surgical fixation to manage this type of fracture has increased, despite insufficient evidence of improved outcomes over non-surgical management. The SWIFFT trial compared the clinical effectiveness of surgical fixation with cast immobilisation and early fixation of fractures that fail to unite in adults with scaphoid waist fractures displaced by 2 mm or less. METHODS: This pragmatic, parallel-group, multicentre, open-label, two-arm, randomised superiority trial included adults (aged 16 years or older) who presented to orthopaedic departments of 31 hospitals in England and Wales with a clear bicortical fracture of the scaphoid waist on radiographs. An independent remote randomisation service used a computer-generated allocation sequence with randomly varying block sizes to randomly assign participants (1:1) to receive either early surgical fixation (surgery group) or below-elbow cast immobilisation followed by immediate fixation if non-union of the fracture was confirmed (cast immobilisation group). Randomisation was stratified by whether or not there was displacement of either a step or a gap of 1-2 mm inclusive on any radiographic view. The primary outcome was the total patient-rated wrist evaluation (PRWE) score at 52 weeks after randomisation, and it was analysed on an available case intention-to-treat basis. This trial is registered with the ISRCTN registry, ISRCTN67901257, and is no longer recruiting, but long-term follow-up is ongoing. FINDINGS: Between July 23, 2013, and July 26, 2016, 439 (42%) of 1047 assessed patients (mean age 33 years; 363 [83%] men) were randomly assigned to the surgery group (n=219) or to the cast immobilisation group (n=220). Of these, 408 (93%) participants were included in the primary analysis (203 participants in the surgery group and 205 participants in the cast immobilisation group). 16 participants in the surgery group and 15 participants in the cast immobilisation group were excluded because of either withdrawal, no response, or no follow-up data at 6, 12, 26, or 52 weeks. There was no significant difference in mean PRWE scores at 52 weeks between the surgery group (adjusted mean 11·9 [95% CI 9·2-14·5]) and the cast immobilisation group (14·0 [11·3 to 16·6]; adjusted mean difference -2·1 [95% CI -5·8 to 1·6], p=0·27). More participants in the surgery group (31 [14%] of 219 participants) had a potentially serious complication from surgery than in the cast immobilisation group (three [1%] of 220 participants), but fewer participants in the surgery group (five [2%]) had cast-related complications than in the cast immobilisation group (40 [18%]). The number of participants who had a medical complication was similar between the two groups (four [2%] in the surgery group and five [2%] in the cast immobilisation group). INTERPRETATION: Adult patients with scaphoid waist fractures displaced by 2 mm or less should have initial cast immobilisation, and any suspected non-unions should be confirmed and immediately fixed with surgery. This treatment strategy will help to avoid the risks of surgery and mostly limit the use of surgery to fixing fractures that fail to unite. FUNDING: National Institute for Health Research Health Technology Assessment Programme.
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Moldes Cirúrgicos , Fixação Interna de Fraturas , Fraturas Ósseas/terapia , Osso Escafoide/lesões , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Parafusos Ósseos , Feminino , Fixação de Fratura , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Fraturas não Consolidadas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Osso Escafoide/cirurgia , Tempo para o Tratamento , Adulto JovemRESUMO
BACKGROUND: The information given to people considering taking part in a trial needs to be easy to understand if those people are to become, and then remain, trial participants. However, there is a tension between providing comprehensive information and providing information that is comprehensible. User-testing is one method of developing better participant information, and there is evidence that user-tested information is better at informing participants about key issues relating to trials. However, it is not clear if user-testing also leads to changes in the rates of recruitment in trials, compared to standard trial information. As part of a programme of research, we embedded 'studies within a trial' (SWATs) across multiple ongoing trials to see if user-tested materials led to better rates of recruitment. METHODS: Seven 'host' trials included a SWAT evaluation and randomised their participants to receive routine information sheets generated by the research teams, or information sheets optimised through user-testing. We collected data on trial recruitment and analysed the results across these trials using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised in a host trial following an invitation to take part. RESULTS: Six SWATs (n=27,805) provided data on recruitment. Optimised participant information sheets likely result in little or no difference in recruitment rates (7.2% versus 6.8%, pooled odds ratio = 1.03, 95% CI 0.90 to 1.19, p-value = 0.63, I2 = 0%). CONCLUSIONS: Participant information sheets developed through user testing did not improve recruitment rates. The programme of work showed that co-ordinated testing of recruitment strategies using SWATs is feasible and can provide both definitive and timely evidence on the effectiveness of recruitment strategies. TRIAL REGISTRATION: Healthlines Depression (ISRCTN14172341) Healthlines CVD (ISRCTN27508731) CASPER (ISRCTN02202951) ISDR (ISRCTN87561257) ECLS (NCT01925625) REFORM (ISRCTN68240461) HeLP Diabetes (ISRCTN02123133).
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Projetos de Pesquisa , Humanos , Razão de Chances , Seleção de PacientesRESUMO
OBJECTIVES: Assess the effectiveness of 5* GRIP-rated slip-resistant footwear in preventing slips in the workplace compared to usual footwear (control group). METHODS: A multicentre, randomised controlled trial; 4553 National Health Service (NHS) staff were randomised 1:1 to the intervention group (provided with 5* GRIP-rated slip-resistant footwear) or the control group. The primary outcome of incidence rate of self-reported slips in the workplace over 14 weeks was analysed using a mixed-effects negative binomial model. Secondary outcome measures included incidence rate of falls from a slip, falls not from a slip, proportion of participants reporting a slip, fall or fracture and time to first slip and fall. RESULTS: 6743 slips were reported: 2633 in the intervention group (mean 1.16 per participant, range 0 to 36) and 4110 in the control group (mean 1.80 per participant, range 0 to 83). There was a statistically significant reduction in slip rate in the intervention group relative to the control group (incidence rate ratio (IRR) 0.63, 95% CI 0.57 to 0.70, p<0.001). Statistically significant differences, in favour of the intervention group, were observed in falls from a slip (IRR 0.51, 95% CI 0.28 to 0.92, p=0.03), the proportion of participants who reported a slip (OR 0.58, 95% CI 0.50 to 0.66, p<0.001) or fall (OR 0.73, 95% CI 0.54 to 0.99, p=0.04) and time to first slip (HR 0.73, 95% CI 0.67 to 0.80, p<0.001). CONCLUSIONS: The offer and provision of 5* GRIP-rated footwear reduced slips in NHS staff in the workplace. TRIAL REGISTRATION NUMBER: ISRCTN33051393.
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BACKGROUND: Despite effective assessment methods and medications targeting osteoporosis and related fractures, screening for fracture risk is not currently advocated in the UK. We tested whether a community-based screening intervention could reduce fractures in older women. METHODS: We did a two-arm randomised controlled trial in women aged 70-85 years to compare a screening programme using the Fracture Risk Assessment Tool (FRAX) with usual management. Women were recruited from 100 general practitioner (GP) practices in seven regions of the UK: Birmingham, Bristol, Manchester, Norwich, Sheffield, Southampton, and York. We excluded women who were currently on prescription anti-osteoporotic drugs and any individuals deemed to be unsuitable to enter a research study (eg, known dementia, terminally ill, or recently bereaved). The primary outcome was the proportion of individuals who had one or more osteoporosis-related fractures over a 5-year period. In the screening group, treatment was recommended in women identified to be at high risk of hip fracture, according to the FRAX 10-year hip fracture probability. Prespecified secondary outcomes were the proportions of participants who had at least one hip fracture, any clinical fracture, or mortality; and the effect of screening on anxiety and health-related quality of life. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN 55814835. FINDINGS: 12â483 eligible women were identified and participated in the trial, and 6233 women randomly assigned to the screening group between April 15, 2008, and July 2, 2009. Treatment was recommended in 898 (14%) of 6233 women. Use of osteoporosis medication was higher at the end of year 1 in the screening group compared with controls (15% vs 4%), with uptake particularly high (78% at 6 months) in the screening high-risk subgroup. Screening did not reduce the primary outcome of incidence of all osteoporosis-related fractures (hazard ratio [HR] 0·94, 95% CI 0·85-1·03, p=0·178), nor the overall incidence of all clinical fractures (0·94, 0·86-1·03, p=0·183), but screening reduced the incidence of hip fractures (0·72, 0·59-0·89, p=0·002). There was no evidence of differences in mortality, anxiety levels, or quality of life. INTERPRETATION: Systematic, community-based screening programme of fracture risk in older women in the UK is feasible, and could be effective in reducing hip fractures. FUNDING: Arthritis Research UK and Medical Research Council.
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Serviços de Saúde Comunitária , Programas de Rastreamento , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Quadril/diagnóstico , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/prevenção & controle , Humanos , Fraturas por Osteoporose/epidemiologia , Modelos de Riscos Proporcionais , Qualidade de Vida , Medição de Risco , Reino UnidoRESUMO
BACKGROUND: Comparisons of baseline covariates in randomised controlled trials whilst often undertaken is regarded by many as an exercise in futility. Because of randomisation the null hypothesis is true for baseline comparisons and therefore any differences will occur by chance. However, this is only the case if allocations are not known in advance of recruitment. If this occurs then selection bias at randomisation may be present and it is possible that the statistical testing of covariates may unveil selection bias. In this paper we show that this is particularly the case for cluster randomised trials when post-randomised recruitment often occurs and can lead to selection bias. MAIN TEXT: We take a recently published cluster randomised trial that has suffered from selection bias due to differential recruitment and calculate baseline p values. We show that statistically significant imbalances of p < 0.0001 occurred in 5 of the 10 covariates. In comparison for an individually randomised trial that had no evidence of selection bias only 1 p value of p < 0.05 out of 20 tests was observed. Had baseline p values for the cluster trial been presented to journal editors, reviewers and readers then the results of the trial might have been treated with more caution. CONCLUSION: We argue that the blanket ban of baseline testing as advocated by some may reduce the chance of identifying deficient cluster randomised trials and this opposition should be reconsidered for cluster trials.
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Seleção de Pacientes , Distribuição Aleatória , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Terapia por Acupuntura , Adolescente , Austrália , Feminino , Humanos , Gravidez , Resultado da Gravidez , Gravidez na Adolescência/prevenção & controle , Viés de Seleção , Incontinência Urinária por Estresse/prevenção & controle , Incontinência Urinária por Estresse/terapiaRESUMO
Background: Synovitis is believed to play a role in producing symptoms in persons with hand osteoarthritis, but data on slow-acting anti-inflammatory treatments are sparse. Objective: To determine the effectiveness of hydroxychloroquine versus placebo as an analgesic treatment of hand osteoarthritis. Design: Randomized, double-blind, placebo-controlled clinical trial with 12-month follow-up. (ISRCTN registry number: ISRCTN91859104). Setting: 13 primary and secondary care centers in England. Participants: Of 316 patients screened, 248 participants (82% women; mean age, 62.7 years) with symptomatic (pain ≥4 on a 0- to 10-point visual analogue scale) and radiographic hand osteoarthritis were randomly assigned and 210 (84.7%) completed the 6-month primary end point. Intervention: Hydroxychloroquine (200 to 400 mg) or placebo (1:1) for 12 months with ongoing usual care. Measurements: The primary end point was average hand pain during the previous 2 weeks (on a 0- to 10-point numerical rating scale [NRS]) at 6 months. Secondary end points included self-reported pain and function, grip strength, quality of life, radiographic structural change, and adverse events. Baseline ultrasonography was done. Results: At 6 months, mean hand pain was 5.49 points in the placebo group and 5.66 points in the hydroxychloroquine group, with a treatment difference of -0.16 point (95% CI, -0.73 to 0.40 point) (P = 0.57). Results were robust to adjustments for adherence, missing data, and use of rescue medication. No significant treatment differences existed at 3, 6, or 12 months for any secondary outcomes. The percentage of participants with at least 1 joint with synovitis was 94% (134 of 143) on grayscale ultrasonography and 59% on power Doppler. Baseline structural damage or synovitis did not affect treatment response. Fifteen serious adverse events were reported (7 in the hydroxychloroquine group [3 defined as possibly related] and 8 in the placebo group). Limitation: Hydroxychloroquine dosage restrictions may have reduced efficacy. Conclusion: Hydroxychloroquine was no more effective than placebo for pain relief in patients with moderate to severe hand pain and radiographic osteoarthritis. Primary Funding Source: Arthritis Research UK.
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Antirreumáticos/uso terapêutico , Mãos , Hidroxicloroquina/uso terapêutico , Osteoartrite/tratamento farmacológico , Método Duplo-Cego , Inglaterra , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Medição da Dor , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Falls are a major cause of morbidity among older people. Multifaceted interventions may be effective in preventing falls and related fractures. OBJECTIVE: To evaluate the cost-effectiveness alongside the REducing Falls with Orthoses and a Multifaceted podiatry intervention (REFORM) trial. METHODS: REFORM was a pragmatic multicentre cohort randomised controlled trial in England and Ireland; 1,010 participants (> 65 years) were randomised to receive either a podiatry intervention (n = 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 (n = 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. RESULTS: 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, p = 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. CONCLUSION: 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.
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Acidentes por Quedas/prevenção & controle , Órtoses do Pé , Podiatria/métodos , Acidentes por Quedas/economia , Idoso , Estudos de Coortes , Análise Custo-Benefício , Inglaterra , Feminino , Órtoses do Pé/economia , Humanos , Irlanda , Masculino , Podiatria/economia , Podiatria/instrumentação , Qualidade de VidaRESUMO
BACKGROUND: Many countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children. The Family Nurse Partnership (FNP) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in England that involves up to 64 structured home visits from early pregnancy until the child's second birthday by specially recruited and trained family nurses. We aimed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth. METHODS: We did a pragmatic, non-blinded, randomised controlled, parallel-group trial in community midwifery settings at 18 partnerships between local authorities and primary and secondary care organisations in England. Eligible participants were nulliparous and aged 19 years or younger, and were recruited at less than 25 weeks' gestation. Field-based researchers randomly allocated mothers (1:1) via remote randomisation (telephone and web) to FNP plus usual care (publicly funded health and social care) or to usual care alone. Allocation was stratified by site and minimised by gestation (<16 weeks vs ≥16 weeks), smoking status (yes vs no), and preferred language of data collection (English vs non-English). Mothers and assessors (local researchers at baseline and 24 months' follow-up) were not masked to group allocation, but telephone interviewers were blinded. Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy, birthweight of the baby, the proportion of women with a second pregnancy within 24 months post-partum, and emergency attendances and hospital admissions for the child within 24 months post-partum. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN23019866. FINDINGS: Between June 16, 2009, and July 28, 2010, we screened 3251 women. After enrolment, 823 women were randomly assigned to receive FNP and 822 to usual care. All follow-up data were retrieved by April 25, 2014. 304 (56%) of 547 women assigned to FNP and 306 (56%) of 545 assigned to usual care smoked at late pregnancy (adjusted odds ratio [AOR] 0·90, 97·5% CI 0·64-1·28). Mean birthweight of 742 babies with mothers assigned to FNP was 3217·4 g (SD 618·0), whereas birthweight of 768 babies assigned to usual care was 3197·5 g (SD 581·5; adjusted mean difference 20·75 g, 97·5% CI -47·73 to 89·23. 587 (81%) of 725 assessed children with mothers assigned to FNP and 577 (77%) of 753 assessed children assigned to usual care attended an emergency department or were admitted to hospital at least once before their second birthday (AOR 1·32, 97·5% CI 0·99-1·76). 426 (66%) of 643 assessed women assigned to FNP and 427 (66%) 646 assigned to usual care had a second pregnancy within 2 years (AOR 1·01, 0·77-1·33). At least one serious adverse event (mainly clinical events associated with pregnancy and infancy period) was reported for 310 (38%) of 808 participants (mother-child) in the usual care group and 357 (44%) of 810 in the FNP group, none of which were considered related to the intervention. INTERPRETATION: Adding FNP to the usually provided health and social care provided no additional short-term benefit to our primary outcomes. Programme continuation is not justified on the basis of available evidence, but could be reconsidered should supportive longer-term evidence emerge. FUNDING: Department of Health Policy Research Programme.
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Enfermagem Familiar , Serviços de Assistência Domiciliar , Enfermagem Materno-Infantil , Adolescente , Peso ao Nascer , Aleitamento Materno , Desenvolvimento Infantil , Serviço Hospitalar de Emergência/estatística & dados numéricos , Inglaterra/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Bem-Estar do Lactente , Recém-Nascido , Gravidez , Autoeficácia , Fumar/epidemiologia , Apoio Social , Adulto JovemRESUMO
BACKGROUND: A scaphoid fracture is the most common type of carpal fracture affecting young active people. The optimal management of this fracture is uncertain. When treated with a cast, 88 to 90 % of these fractures unite; however, for the remaining 10-12 % the non-union almost invariably leads to arthritis. The alternative is surgery to fix the scaphoid with a screw at the outset. METHODS/DESIGN: We will conduct a randomised controlled trial (RCT) of 438 adult patients with a "clear" and "bicortical" scaphoid waist fracture on plain radiographs to evaluate the clinical effectiveness and cost-effectiveness of plaster cast treatment (with fixation of those that fail to unite) versus early surgical fixation. The plaster cast treatment will be immobilisation in a below elbow cast for 6 to 10 weeks followed by mobilisation. If non-union is confirmed on plain radiographs and/or Computerised Tomogram at 6 to 12 weeks, then urgent surgical fixation will be performed. This is being compared with immediate surgical fixation with surgeons using their preferred technique and implant. These treatments will be undertaken in trauma units across the United Kingdom. The primary outcome and end-point will be the Patient Rated Wrist Evaluation (a patient self-reported assessment of wrist pain and function) at 52 weeks and also measured at 6, 12, 26 weeks and 5 years. Secondary outcomes include an assessment of radiological union of the fracture; quality of life; recovery of wrist range and strength; and complications. We will also qualitatively investigate patient experiences of their treatment. DISCUSSION: Scaphoid fractures are an important public health problem as they predominantly affect young active individuals in the more productive working years of their lives. Non-union, if untreated, can lead to arthritis which can disable patients at a very young age. There is a rapidly increasing trend for immediate surgical fixation of these fractures but there is insufficient evidence from existing RCTs to support this. The SWIFFT Trial is a rigorously designed and adequately powered study which aims to contribute to the evidence-base to inform clinical decisions for the treatment of this common fracture in adults. TRIAL REGISTRATION: The trial is registered with the International Standard Randomised Controlled Trial Register ( ISRCTN67901257 ). Date registration assigned was 13/02/2013.
Assuntos
Moldes Cirúrgicos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Fraturas Mal-Unidas/prevenção & controle , Osso Escafoide/lesões , Traumatismos do Punho/cirurgia , Adulto , Parafusos Ósseos , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/instrumentação , Fraturas Ósseas/diagnóstico por imagem , Fraturas Mal-Unidas/complicações , Humanos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Radiografia , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Osso Escafoide/diagnóstico por imagem , Osso Escafoide/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Reino Unido , Traumatismos do Punho/diagnóstico por imagem , Articulação do Punho/fisiologia , Adulto JovemRESUMO
BACKGROUND: Management of chronic neck pain may benefit from additional active self-care-oriented approaches. OBJECTIVE: To evaluate clinical effectiveness of Alexander Technique lessons or acupuncture versus usual care for persons with chronic, nonspecific neck pain. DESIGN: Three-group randomized, controlled trial. (Current Controlled Trials: ISRCTN15186354). SETTING: U.K. primary care. PARTICIPANTS: Persons with neck pain lasting at least 3 months, a score of at least 28% on the Northwick Park Questionnaire (NPQ) for neck pain and associated disability, and no serious underlying pathology. INTERVENTION: 12 acupuncture sessions or 20 one-to-one Alexander lessons (both 600 minutes total) plus usual care versus usual care alone. MEASUREMENTS: NPQ score (primary outcome) at 0, 3, 6, and 12 months (primary end point) and Chronic Pain Self-Efficacy Scale score, quality of life, and adverse events (secondary outcomes). RESULTS: 517 patients were recruited, and the median duration of neck pain was 6 years. Mean attendance was 10 acupuncture sessions and 14 Alexander lessons. Between-group reductions in NPQ score at 12 months versus usual care were 3.92 percentage points for acupuncture (95% CI, 0.97 to 6.87 percentage points) (P = 0.009) and 3.79 percentage points for Alexander lessons (CI, 0.91 to 6.66 percentage points) (P = 0.010). The 12-month reductions in NPQ score from baseline were 32% for acupuncture and 31% for Alexander lessons. Participant self-efficacy improved for both interventions versus usual care at 6 months (P < 0.001) and was significantly associated (P < 0.001) with 12-month NPQ score reductions (acupuncture, 3.34 percentage points [CI, 2.31 to 4.38 percentage points]; Alexander lessons, 3.33 percentage points [CI, 2.22 to 4.44 percentage points]). No reported serious adverse events were considered probably or definitely related to either intervention. LIMITATION: Practitioners belonged to the 2 main U.K.-based professional associations, which may limit generalizability of the findings. CONCLUSION: Acupuncture sessions and Alexander Technique lessons both led to significant reductions in neck pain and associated disability compared with usual care at 12 months. Enhanced self-efficacy may partially explain why longer-term benefits were sustained. PRIMARY FUNDING SOURCE: Arthritis Research UK.
Assuntos
Terapia por Acupuntura , Dor Crônica/terapia , Cervicalgia/terapia , Autocuidado , Terapia por Acupuntura/efeitos adversos , Terapia por Acupuntura/métodos , Dor Crônica/economia , Feminino , Gastos em Saúde , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Cervicalgia/economia , Visita a Consultório Médico/estatística & dados numéricos , Cooperação do Paciente , Medicamentos sob Prescrição , Autocuidado/efeitos adversos , Autocuidado/métodos , Autoeficácia , Resultado do TratamentoRESUMO
BACKGROUND: Drawbacks exist with the standard treatment (four-layer compression bandages) for venous leg ulcers. We have therefore compared the clinical effectiveness and cost-effectiveness of two-layer compression hosiery with the four-layer bandage for the treatment of such ulcers. METHODS: We undertook this pragmatic, open, randomised controlled trial with two parallel groups in 34 centres in England and Northern Ireland. The centres were community nurse teams or services, family doctor practices, leg ulcer clinics, tissue viability clinics or services, and wound clinics. Participants were aged 18 years or older with a venous leg ulcer and an ankle brachial pressure index of at least 0·8, and were tolerant of high compression. We randomly allocated participants (1:1) to receive two-layer compression hosiery or a four-layer bandage, using a remote randomisation service and prevalidated computer randomisation program. Participants were stratified by ulcer duration and ulcer area with permuted blocks (block sizes four and six). The primary endpoint was time to ulcer healing, with a maximum follow-up of 12 months. Although participants and health-care providers were not masked to treatment allocation, the primary endpoint was measured by masked assessment of photographs. Primary analysis was intention to treat with Cox regression, with adjustment for ulcer area, ulcer duration, physical mobility, and centre. This trial is registered with the ISRCTN register, number ISRCTN49373072. FINDINGS: We randomly allocated 457 participants to the two treatment groups: 230 to two-layer hosiery and 227 to the four-layer bandage, of whom 453 (230 hosiery and 223 bandage) contributed data for analysis. Median time to ulcer healing was 99 days (95% CI 84-126) in the hosiery group and 98 days (85-112) in the bandage group, and the proportion of ulcers healing was much the same in the two groups (70·9% hosiery and 70·4% bandage). More hosiery participants changed their allocated treatment (38·3% hosiery vs 27·0% bandage; p=0·02). 300 participants had 895 adverse events, of which 85 (9·5%) were classed as serious but unrelated to trial treatment. INTERPRETATION: Two-layer compression hosiery is a viable alternative to the four-layer bandage-it is equally as effective at healing venous leg ulcers. However, a higher rate of treatment changes in participants in the hosiery group than in the bandage group suggests that hosiery might not be suitable for all patients. FUNDING: NIHR Health Technology Assessment programme (07/60/26).
Assuntos
Bandagens Compressivas , Úlcera Varicosa/terapia , Idoso , Idoso de 80 Anos ou mais , Bandagens Compressivas/efeitos adversos , Bandagens Compressivas/economia , Análise Custo-Benefício , Inglaterra , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Irlanda do Norte , Anos de Vida Ajustados por Qualidade de Vida , Meias de Compressão/efeitos adversos , Meias de Compressão/economia , Resultado do Tratamento , Úlcera Varicosa/economia , CicatrizaçãoRESUMO
BACKGROUND: About 90 % of patients with intra-thoracic malignancy experience breathlessness. Breathing training is helpful, but it is unknown whether repeated sessions are needed. The present study aims to test whether three sessions are better than one for breathlessness in this population. METHODS: This is a multi-centre randomised controlled non-blinded parallel arm trial. Participants were allocated to three sessions or single (1:2 ratio) using central computer-generated block randomisation by an independent Trials Unit and stratified for centre. The setting was respiratory, oncology or palliative care clinics at eight UK centres. Inclusion criteria were people with intrathoracic cancer and refractory breathlessness, expected prognosis ≥3 months, and no prior experience of breathing training. The trial intervention was a complex breathlessness intervention (breathing training, anxiety management, relaxation, pacing, and prioritisation) delivered over three hour-long sessions at weekly intervals, or during a single hour-long session. The main primary outcome was worst breathlessness over the previous 24 hours ('worst'), by numerical rating scale (0 = none; 10 = worst imaginable). Our primary analysis was area under the curve (AUC) 'worst' from baseline to 4 weeks. All analyses were by intention to treat. RESULTS: Between April 2011 and October 2013, 156 consenting participants were randomised (52 three; 104 single). Overall, the 'worst' score reduced from 6.81 (SD, 1.89) to 5.84 (2.39). Primary analysis [n = 124 (79 %)], showed no between-arm difference in the AUC: three sessions 22.86 (7.12) vs single session 22.58 (7.10); P value = 0.83); mean difference 0.2, 95 % CIs (-2.31 to 2.97). Complete case analysis showed a non-significant reduction in QALYs with three sessions (mean difference -0.006, 95 % CIs -0.018 to 0.006). Sensitivity analyses found similar results. The probability of the single session being cost-effective (threshold value of £20,000 per QALY) was over 80 %. CONCLUSIONS: There was no evidence that three sessions conferred additional benefits, including cost-effectiveness, over one. A single session of breathing training seems appropriate and minimises patient burden. TRIAL REGISTRATION: Registry: ISRCTN; TRIAL REGISTRATION NUMBER: ISRCTN49387307; http://www.isrctn.com/ISRCTN49387307 ; registration date: 25/01/2011.
Assuntos
Exercícios Respiratórios/economia , Exercícios Respiratórios/métodos , Dispneia/reabilitação , Neoplasias Pulmonares/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Dispneia/etiologia , Feminino , Humanos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/economia , Cuidados Paliativos/métodos , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND: Despite widespread popularity, text messaging has rarely been used for data collection in clinical research. This paper reports on the development, feasibility, acceptability, validity, and discriminant utility of a single item depression rating scale, delivered weekly via an automated SMS system, as part of a large randomised controlled trial. METHODS: 755 depressed patients (BDI-II score ≥20) were recruited from primary care into a randomised trial of acupuncture versus counselling or usual care, and invited to opt into a repeated-measures text messaging sub-study. Two weeks following random allocation, trial participants were sent a weekly text message for 15 weeks. Texts were a single question asking, on a scale from 1 to 9, the extent to which they felt depressed. Feasibility and acceptability of the automated SMS system were evaluated according to cost, ease of implementation, proportion consenting, response rates, and qualitative feedback. Concurrent validity was estimated by correlating SMS responses with the Patient Health Questionnaire (PHQ-9). SMS responses were compared between groups over time to explore treatment effects. RESULTS: 527 (69.8%) trial participants consented to the texting sub-study, of whom 498 (94.5%) responded to at least one message. Participants provided a valid response to an average of 12.5 messages. Invalid responses accounted for 1.1% of texts. The automated SMS system was quick to set-up, inexpensive, and well received. Comparison of PHQ-9 and SMS responses at 3 months demonstrated a moderate to high degree of agreement (Kendall's tau-b = 0.57, p < 0.0001, n = 220). SMS depression scores over the 15 weeks differed significantly between trial arms (p = 0.007), with participants allocated to the acupuncture and counselling arms reporting improved depression outcomes compared to usual GP care alone, which reached statistical significance ten weeks after randomisation. Overall, the single item SMS scale also appeared more responsive to changes in depression, resulting from treatment, than the PHQ-9. CONCLUSIONS: Automated SMS systems offer a feasible and acceptable means of monitoring depression within clinical research. This study provides clear evidence to support the regular use of a simple SMS scale as a sensitive and valid outcome measure of depression within future randomised controlled trials. TRIAL REGISTRATION: Current Controlled Trials - ISRCTN63787732 http://www.controlled-trials.com/ISRCTN63787732/ACUDEP Date of registration: 15/12/2009.
Assuntos
Transtorno Depressivo/terapia , Envio de Mensagens de Texto , Terapia por Acupuntura/métodos , Adulto , Aconselhamento/métodos , Coleta de Dados/métodos , Estudos de Viabilidade , Feminino , Medicina Geral/métodos , Humanos , Masculino , Satisfação do Paciente , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
IMPORTANCE: The need for surgery for the majority of patients with displaced proximal humeral fractures is unclear, but its use is increasing. OBJECTIVE: To evaluate the clinical effectiveness of surgical vs nonsurgical treatment for adults with displaced fractures of the proximal humerus involving the surgical neck. DESIGN, SETTING, AND PARTICIPANTS: A pragmatic, multicenter, parallel-group, randomized clinical trial, the Proximal Fracture of the Humerus Evaluation by Randomization (PROFHER) trial, recruited 250 patients aged 16 years or older (mean age, 66 years [range, 24-92 years]; 192 [77%] were female; and 249 [99.6%] were white) who presented at the orthopedic departments of 32 acute UK National Health Service hospitals between September 2008 and April 2011 within 3 weeks after sustaining a displaced fracture of the proximal humerus involving the surgical neck. Patients were followed up for 2 years (up to April 2013) and 215 had complete follow-up data. The data for 231 patients (114 in surgical group and 117 in nonsurgical group) were included in the primary analysis. INTERVENTIONS: Fracture fixation or humeral head replacement were performed by surgeons experienced in these techniques. Nonsurgical treatment was sling immobilization. Standardized outpatient and community-based rehabilitation was provided to both groups. MAIN OUTCOMES AND MEASURES: Primary outcome was the Oxford Shoulder Score (range, 0-48; higher scores indicate better outcomes) assessed during a 2-year period, with assessment and data collection at 6, 12, and 24 months. Sample size was based on a minimal clinically important difference of 5 points for the Oxford Shoulder Score. Secondary outcomes were the Short-Form 12 (SF-12), complications, subsequent therapy, and mortality. RESULTS: There was no significant mean treatment group difference in the Oxford Shoulder Score averaged over 2 years (39.07 points for the surgical group vs 38.32 points for the nonsurgical group; difference of 0.75 points [95% CI, -1.33 to 2.84 points]; P = .48) or at individual time points. There were also no significant between-group differences over 2 years in the mean SF-12 physical component score (surgical group: 1.77 points higher [95% CI, -0.84 to 4.39 points]; P = .18); the mean SF-12 mental component score (surgical group: 1.28 points lower [95% CI, -3.80 to 1.23 points]; P = .32); complications related to surgery or shoulder fracture (30 patients in surgical group vs 23 patients in nonsurgical group; P = .28), requiring secondary surgery to the shoulder (11 patients in both groups), and increased or new shoulder-related therapy (7 patients vs 4 patients, respectively; P = .58); and mortality (9 patients vs 5 patients; P = .27). Ten medical complications (2 cardiovascular events, 2 respiratory events, 2 gastrointestinal events, and 4 others) occurred in the surgical group during the postoperative hospital stay. CONCLUSIONS AND RELEVANCE: Among patients with displaced proximal humeral fractures involving the surgical neck, there was no significant difference between surgical treatment compared with nonsurgical treatment in patient-reported clinical outcomes over 2 years following fracture occurrence. These results do not support the trend of increased surgery for patients with displaced fractures of the proximal humerus. TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN50850043.