Health technology assessment最新文献

Background: This review assessed the clinical- and cost-effectiveness of point-of-care tests to guide the initial management of people presenting with suspected acute respiratory infection.

Methods: Searches for systematic reviews, randomised controlled trials and cost-utility studies were conducted in May 2023. Sources included MEDLINE, Epistemonikos, EMBASE, Cochrane Central Register of Controlled Trials, the Cost-effectiveness Analysis Registry and reference checking. Eligible studies included people (≥ 16 years) making initial contact with the health system with symptoms suggestive of acute respiratory infection. Risk of bias in randomised controlled trials was assessed using the Cochrane risk-of-bias tool. The Drummond checklist was used for cost-utility studies. Meta-analyses of clinical outcomes were conducted to estimate summary risk ratios with 95% confidence intervals. Study characteristics and main results were summarised narratively and tabulated.

Results: Fourteen randomised controlled trials were included; all had a high risk of bias. Ten randomised controlled trials analysed point-of-care tests for C-reactive protein. Compared with usual care, the effects on hospital admissions and mortality were highly uncertain due to sparse data. Three randomised controlled trials had heterogeneous findings on the resolution of symptoms/time to full recovery. The risk of re-consultations increased in patients receiving C-reactive protein point-of-care tests (pooled risk ratio 1.61, 95% confidence interval 1.07 to 2.41; four studies). There was a reduction in antibiotics initially prescribed (C-reactive protein point-of-care tests vs. usual care: pooled risk ratio 0.75, 95% confidence interval 0.68 to 0.84; nine studies). The effects of procalcitonin point-of-care tests compared with usual care on hospital admission, escalation of care, and duration of symptoms were very uncertain as only one randomised controlled trial was included. The study found a large reduction in antibiotic prescriptions within 7 days. Two studies revealed a large reduction in initial antibiotic prescriptions for Group A streptococcus point-of-care tests versus usual care. Only one study compared an influenza point-of-care test with usual care. The effect of the antibiotics prescribed was very uncertain. No deaths occurred in either treatment group.

Cost-effectiveness: Six of the 17 included cost-utility studies were judged to be directly applicable to our review, 4 of which focused on the C-reactive protein point-of-care test. The results suggested that the C-reactive protein point-of-care test is potentially cost-effective; these studies were generally limited to capturing only short-term costs and consequences. One study evaluated 14 different point-of-care tests for Group A streptococcus; none were cost-effective compared with usual care. A further study evaluated two rapid tests (

Background: Fibromyalgia is a chronic condition characterised by widespread musculoskeletal pain. Sleep problems are reported by 92% of people living with fibromyalgia.

Objectives: To evaluate the effectiveness and safety of interventions for the management of fibromyalgia-related sleep problems; explore the experiences of people with fibromyalgia-related sleep problems and examine the content of patient-reported outcome measures for 'sleep quality'.

Methods: We conducted: (1) a network meta-analysis of randomised controlled trials to compare the effectiveness of pharmacological and non-pharmacological interventions; (2) a systematic thematic synthesis of qualitative evidence; (3) a content analysis of existing patient-reported outcome measures validated in people with fibromyalgia. Major electronic databases were searched in November 2021.

Results: One hundred and sixty-eight studies were included in the effectiveness synthesis. The network meta-analysis assessing sleep quality included 35 treatment categories from 65 studies (8247 participants). Most studies were at high overall risk of bias. There is some evidence that compared with placebo or sham treatments, some forms of exercise [i.e. land-based aerobic exercise training in combination with flexibility training (standardised mean difference -4.69, credible interval -8.14 to -1.28) and aquatic-based aerobic exercise training (standardised mean difference -2.63, credible interval -4.74 to -0.58)] may improve sleep. There is also a suggestion that land-based strengthening exercise, psychological and behavioural therapies with a focus on sleep, electrotherapy, weight loss, dental splints, antipsychotics and tricyclics may have a modest effect on sleep, but credible intervals are wide. For other interventions, there is no clear evidence of beneficial effects on sleep. Our certainty of current evidence was predominantly low to very low. The thematic synthesis highlighted the bidirectional relationship between sleep and pain. Twenty-one sleep domains were identified across five patient-reported outcome measures. The domain most frequently identified was sleep maintenance. The Pittsburgh Sleep Quality Index was the most comprehensive tool (15 domains), followed by the Medical Outcomes Study Sleep Scale (11 domains).

Limitations: Quantitative studies varied considerably in terms of characteristics of interventions, control treatments and type of outcome measures. In the network, most interventions were compared with placebo, sham treatment or usual care and not with another active treatment. In general, studies were small, unblinded and of short duration (median 12 weeks). For the qualitative synthesis and patient-reported outcome measures analysis, it is unclear whether study participants are adequately representative of the wider population of fibromyalgia patients due to poor reporting

Background: Lithium and several atypical antipsychotics are the recommended first-line augmentation options for treatment-resistant depression; however, few studies have compared them directly, and none for longer than 8 weeks. Consequently, there is little evidence-based guidance for clinicians when choosing an augmentation option for patients with treatment-resistant depression.

Objectives: This trial examined whether it is more clinically and cost-effective to prescribe lithium or quetiapine augmentation therapy for patients with treatment-resistant depression over 12 months.

Design: This was a parallel group, multicentre, pragmatic, open-label superiority trial comparing the clinical and cost-effectiveness of lithium versus quetiapine augmentation of antidepressant medication in treatment-resistant depression. Participants were randomised 1 : 1 at baseline to the decision to prescribe either lithium or quetiapine.

Setting: Six National Health Service trusts in England.

Participants: Eligible participants were aged ≥ 18 years, met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for major depressive disorder, scored ≥ 14 on the 17-item Hamilton Depression Rating Scale and whose depression had had an inadequate response to at least two therapeutic antidepressant treatment trials in the current episode, with a current antidepressant treatment at or above the therapeutic dose for ≥ 6 weeks. Patients with a history of psychosis or bipolar disorder were excluded. Patients were judged suitable for either treatment.

Interventions: After randomisation, pre-prescribing safety checks were undertaken as per standard care and trial clinicians decided whether to proceed with prescribing the allocated medication. Trial clinicians received recommendations for titration and dosing in line with current clinical guidelines; however, dosing regimens could be altered according to tolerability and response. Participants were followed up using weekly self-report questionnaires and 8-, 26- and 52-week research visits.

Main outcome measures: The co-primary outcome measures were depressive symptom severity over 52 weeks, measured weekly using the self-rated Quick Inventory of Depressive Symptomatology, and time to all-cause treatment discontinuation of the trial medication. Economic analyses compared costs between the two treatment arms over 52 weeks, from a National Health Service and Personal Social Services perspective, and a societal perspective.

Results: Two hundred and twelve participants were randomised, 107 to quetiapine and 105 to lithium. The quetiapine arm showed a significantly greater reduction in depressive symptoms than the lithium arm over 52 weeks (quetiapine vs. lithium area under the differences curve = -68.36, 95% confidence interval:

Background: Ovarian and tubal cancers are lethal gynaecological cancers, with over 50% of the patients diagnosed at advanced stage.

Trial design: Randomised controlled trial involving 27 primary care trusts adjacent to 13 trial centres based at NHS Trusts in England, Wales and Northern Ireland.

Methods: Postmenopausal average-risk women, aged 50-74, with intact ovaries and no previous ovarian or current non-ovarian cancer.

Interventions: One of two annual screening strategies: (1) multimodal screening (MMS) using a longitudinal CA125 algorithm with repeat CA125 testing and transvaginal scan (TVS) as second line test (2) ultrasound screening (USS) using TVS alone with repeat scan to confirm any abnormality. The control (C) group had no screening. Follow-up was through linkage to national registries, postal follow-up questionnaires and direct communication with trial centres and participants.

Objective: To assess comprehensively risks and benefits of ovarian cancer screening in the general population.

Outcome: Primary outcome was death due to ovarian or tubal cancer as assigned by an independent outcomes review committee. Secondary outcomes included incidence and stage at diagnosis of ovarian and tubal cancer, compliance, performance characteristics, harms and cost-effectiveness of the two screening strategies and a bioresource for future research.

Randomisation: The trial management system confirmed eligibility and randomly allocated participants using computer-generated random numbers to MMS, USS and C groups in a 1:1:2 ratio.

Blinding: Investigators and participants were unblinded and outcomes review committee was masked to randomisation group.

Analyses: Primary analyses were by intention to screen, comparing separately MMS and USS with C using the Versatile test.

Results: 1,243,282 women were invited and 205,090 attended for recruitment between April 2001 and September 2005.

Randomised: 202,638 women: 50,640 MMS, 50,639 USS and 101,359 C group.

Numbers analysed for primary outcome: 202,562 (>99.9%): 50,625 (>99.9%) MMS, 50,623 (>99.9%) USS, and 101,314 (>99.9%) C group.

Outcome: Women in MMS and USS groups underwent 345,570 and 327,775 annual screens between randomisation and 31 December 2011. At median follow-up of 16.3 (IQR 15.1-17.3) years, 2055 women developed ovarian or tubal cancer: 522 (1.0% of 50,625) MMS, 517 (1.0% of 50,623) USS, and 1016 (1.0% of 101314) in C group. Compared to the C group, in the MMS group, the incidence of Stage I/II disease was 39.2% (95% CI 16.1 to 66.9) higher and stage III/IV 10.2% (95% CI -21.3 to 2.4) lower. There was no difference in stage in the USS group. 1206 women died of the disease: 296 (0.6%) MMS, 291 (0.6%) US

Background: Coronavirus disease 2019 devastated lives in care homes for older people, where residents faced higher mortality risks than the general population. Infection prevention and control decisions were critical to protect these vulnerable residents. Infection prevention and control measures like 'lockdowns' had their own risks, such as social isolation, alongside assumed benefits. A key non-pharmaceutical intervention for managing infections is contact tracing. Traditional contact tracing, which relies on recalling contacts, is not feasible in care homes where approximately 70% of residents have cognitive impairments. The CONtact TrAcing in Care homes using digital Technology intervention introduces Bluetooth-enabled wearable devices for automated contact tracing. We provided structured reports (scheduled regularly and in reaction to positive COVID-19 cases) on contact patterns to homes to support better-informed infection prevention and control decisions and potentially reduce blanket restrictive measures. We also partnered with the PROTECT COVID-19 research team to examine air quality in two of our homes.

Methods: CONTACT was a non-randomised mixed-method feasibility study in four English care homes. Recruitment was via care home research networks, with individual consent. Data collection included routine device data, case report forms, qualitative interviews, field observations of care home activity and an adapted Normalisation Measure Development questionnaire survey to explore implementation using normalisation process theory. Quantitative data were analysed using descriptive statistical methods, and qualitative data were thematically analysed using normalisation process theory. Intervention and study delivery were evaluated against predefined progression criteria.

Results: Of 156 eligible residents, 105 agreed to wear a device, with 102 (97%) starting the intervention. Of 225 eligible staff, 82.4% (n = 178) participated. Over 2 months, device loss and battery failure were significant: residents lost 11% of devices, with half replaced. Staff lost fewer devices, just 6.5%, but < 10% were replaced. Fob wearables needed more battery changes than card-type devices (15% vs. 0%). Homes variably understood structured and reactive feedback but were unlikely to act on it. Researcher support for interpreting reports was valued. Homes found information useful when it confirmed rather than challenged preconceived contact patterns. Staff privacy concerns were a barrier to adoption. Study procedures added to existing work, making participation burdensome. The perceived burden of participation, amplified by the pandemic context, outweighed the benefits. CONTACT did not meet its quantitative or qualitative progression criteria.

Limitations: Researchers had to pragmatically adapt procedures, resulting in suboptimal implementation choices from an implementati

Background: Procalcitonin is a biomarker specific for bacterial infection, with a more rapid response than other commonly used biomarkers, such as C-reactive protein, but it is not routinely used in the National Health Service.

Objective: To determine if using a procalcitonin-guided algorithm may safely reduce duration of antibiotic therapy compared to standard of care in hospitalised children with suspected or confirmed infection.

Design: A pragmatic, multicentre, open-label, parallel two-arm, individually randomised controlled trial with internal pilot phase, qualitative study and health economic evaluations.

Setting: Paediatric wards or paediatric intensive care units within children's hospitals (n = 6) and district general hospitals (n = 9) in the United Kingdom.

Participants: Children aged between 72 hours and 18 years admitted to hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection.

Interventions: Procalcitonin-guided algorithm versus usual standard care alone.

Main outcome measures: Coprimary outcomes were duration of intravenous antibiotic use and a composite safety measure.

Results: Between 11 June 2018 and 12 October 2022, 1949 children were recruited: 977 to the procalcitonin group [427 female (43.7%), 550 male (56.3%)], and 972 to the usual care group [478 female (49.2%), 494 male (50.8%)]. Duration of intravenous antibiotics was not significantly different between the procalcitonin group (median 96.0 hours) and the usual care group (median 99.7 hours) [hazard ratio = 0.96 (0.87, 1.05)], and the procalcitonin-guided algorithm was non-inferior to usual care [risk difference = -0.81% (95% confidence interval upper bound 1.11%)]. At clinical review, a procalcitonin result was available for 81.8% of the time, which was considered as part of clinical decision-making 66.6% of the time, and the algorithm was adhered to 57.2% of the time. Incremental cost-effectiveness ratio per duration of intravenous antibiotics hour avoided from bootstrapped samples was £467.62 per intravenous antibiotic hour avoided. Cost analysis of complete cases was also higher in the procalcitonin arm for all age groups, and for children aged 5 years and over. The intervention is not cost-effective as it is more expensive with no significant improvement in intravenous antibiotic duration.

Limitations: Robust antimicrobial stewardship programmes were already implemented in the lead recruiting sites, and adherence to the algorithm was poor. Clinicians may be reluctant to adhere to biomarker-guided algorithms, due to unfamiliarity with interpreting the test result.

Conclusions: In children hospitalised with confirmed or suspected bacterial infection, the addition of a procalcitonin-gui

Background: Coronavirus disease-2019 was associated with significant mortality and morbidity in care homes in 2020-1. Repurposed antiviral drugs might reduce morbidity and mortality through reducing viral transmission, infection, replication and inflammation. We aimed to compare the safety and efficacy of potential antiviral drugs in care home residents.

Methods: We designed a cluster-randomised, open-label, blinded end-point platform trial to test drugs in a postexposure prophylaxis paradigm. Participants aged 65+ years from United Kingdom care homes, with or without nursing, were eligible for participation. Care homes were to be allocated at random by computer to administer 42 days of antiviral agent (ciclesonide or niclosamide) plus standard care versus standard care alone to residents. The primary outcome at 60 days after randomisation comprised the most serious outcome, which was defined as all-cause mortality, all-cause hospitalisation, severe acute respiratory syndrome coronavirus 2 infection or no infection. Analysis would be by intention to treat using ordinal logistic regression. Other outcomes included individual components of the primary outcome, transmission, plus health economic and process evaluation outcomes. The planned sample size was 300 care homes corresponding to 9600 residents. With ~40% of care homes predicted to develop an outbreak during the trial, we needed to recruit 750 homes/24,000 residents.

Results: We initiated the trial including protocol, approvals, insurance, website, database, data algorithms, intervention selection and training materials. We built a network of principal investigators and staff (91) and care homes (299) to support the trial. However, we never contracted care homes or general practitioners since the trial was stopped in September 2021, as vaccination in care homes had significantly reduced infections. Multiple delays significantly delayed the start date, such as: (1) reduced prioritisation of pandemic trials in 2021; (2) cumbersome mechanisms for choosing the investigational medicinal products; (3) contracting between National Institute for Health and Care Research and the investigational medicinal product manufacturers; (4) publicising the investigational medicinal products; (5) identification of sufficient numbers of care homes; (6) identification and contracting with several thousand general practitioners; (7) limited research nurse availability and (8) identification of adequate insurance to cover care homes for research. Generic challenges included working across the four home nations with their different structures and regulations.

Limitations: The feasibility of contracting between the sponsor and the principal investigators, general practitioners and care homes; screening, consent and treatment of care home residents; data acquisition and the potential benefit of postexposure prophylaxis were never t