Consideration of factors associated with inequalities in interventions that support health-care professionals' interaction with patients to reduce inappropriate antimicrobial use: a systematic review.

BACKGROUND: Tackling the public health challenge of antimicrobial resistance (AMR) requires promotion of appropriate antimicrobial use by health-care professionals. The objective of this review was to identify interventions that facilitate appropriate antimicrobial behaviours when health-care professionals interact with patients and any considerations for factors associated with health inequalities. METHODS: For this systematic review, we searched electronic databases (MEDLINE, EMBASE, Web of Science and Google Scholar) from Jan 31, 2023, to Feb 8, 2023. We included search terms such as antimicrobial use/prescribing, health-care professionals, and AMR programmes. We included any relevant primary study published from year 2010 and in English. We conducted forward and backward citation searching from included studies on March 27, 2023. We extracted information on the interventions following the Template for Intervention Description and Replication (TIDieR) guideline and examined reports on how the interventions might impact on inequalities. We performed quality assessment using the Mixed Methods Appraisal Tool (MMAT). We conducted descriptive synthesis. The protocol is registered with PROSPERO (CRD42023395642). FINDINGS: After screening 4979 records, we included 59 studies. Most studies were randomised trials (n=25) and qualitative/mixed methods studies (n=16). Included studies covered 16 countries, particularly the UK (n=16) and the USA (n=13). Most studies (n=34) fulfilled at least 80% of the relevant quality criteria, but 12 studies fulfilled less than 50%. Many interventions were established strategies (eg, TARGET: Treat Antibiotics Responsibly, Guidance, Education and Tools). Patient interaction elements of the interventions often involved using education materials (eg, digital/paper leaflets, and videos) and point-of-care testing. While many studies (n=49) included participants from disadvantaged groups, only three examined how outcomes differ between groups. In those studies, antimicrobial prescription was not associated with age, sex, and level of learning disability. Some other studies reported issues with language barriers and potential digital exclusion, especially for older people. INTERPRETATION: We might have missed some relevant studies due to publication year and language restrictions. Notwithstanding, this review showed that the potential impact of factors associated with health inequalities are not routinely considered during the implementation and evaluation of interventions to improve health-care professionals' interaction with patients. Future work should routinely consider this to help mitigate potential inequalities. FUNDING: UK Health Security Agency.

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: A randomized controlled trial.

AIM: The aim was to determine whether specialist-led habit training using Habit Training with Biofeedback (HTBF) is more effective than specialist-led habit training alone (HT) for chronic constipation and whether outcomes of interventions are improved by stratification to HTBF or HT based on diagnosis (functional defaecation disorder vs. no functional defaecation disorder) by radio-physiological investigations (INVEST). METHOD: This was a parallel three-arm randomized single-blinded controlled trial, permitting two randomized comparisons: HTBF versus HT alone; INVEST- versus no-INVEST-guided intervention. The inclusion criteria were age 18-70 years; attending specialist hospitals in England; self-reported constipation for >6 months; refractory to basic treatment. The main exclusions were secondary constipation and previous experience of the trial interventions. The primary outcome was the mean change in Patient Assessment of Constipation Quality of Life score at 6 months on intention to treat. The secondary outcomes were validated disease-specific and psychological questionnaires and cost-effectiveness (based on EQ-5D-5L). RESULTS: In all, 182 patients were randomized 3:3:2 (target 384): HT n = 68; HTBF n = 68; INVEST-guided treatment n = 46. All interventions had similar reductions (improvement) in the primary outcome at 6 months (approximately -0.8 points of a 4-point scale) with no statistically significant difference between HT and HTBF (-0.03 points; 95% CI -0.33 to 0.27; P = 0.85) or INVEST versus no-INVEST (0.22; -0.11 to 0.55; P = 0.19). Secondary outcomes showed a benefit for all interventions with no evidence of greater cost-effectiveness of HTBF or INVEST compared with HT. CONCLUSION: The results of the study at 6 months were inconclusive. However, with the caveat of under-recruitment and further attrition at 6 months, a simple, cheaper approach to intervention may be as clinically effective and more cost-effective than more complex and invasive approaches.

Testing strategies for Lynch syndrome in people with endometrial cancer: systematic reviews and economic evaluation.

BACKGROUND: Lynch syndrome is an inherited genetic condition that is associated with an increased risk of certain cancers. The National Institute for Health and Care Excellence has recommended that people with colorectal cancer are tested for Lynch syndrome. Routine testing for Lynch syndrome among people with endometrial cancer is not currently conducted. OBJECTIVES: To systematically review the evidence on the test accuracy of immunohistochemistry- and microsatellite instability-based strategies to detect Lynch syndrome among people who have endometrial cancer, and the clinical effectiveness and the cost-effectiveness of testing for Lynch syndrome among people who have been diagnosed with endometrial cancer. DATA SOURCES: Searches were conducted in the following databases, from inception to August 2019 - MEDLINE ALL, EMBASE (both via Ovid), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (both via Wiley Online Library), Database of Abstracts of Reviews of Effects, Health Technology Assessment Database (both via the Centre for Reviews and Dissemination), Science Citation Index, Conference Proceedings Citation Index - Science (both via Web of Science), PROSPERO international prospective register of systematic reviews (via the Centre for Reviews and Dissemination), NHS Economic Evaluation Database, Cost-Effectiveness Analysis Registry, EconPapers (Research Papers in Economics) and School of Health and Related Research Health Utilities Database. The references of included studies and relevant systematic reviews were also checked and experts on the team were consulted. REVIEW METHODS: Eligible studies included people with endometrial cancer who were tested for Lynch syndrome using immunohistochemistry- and/or microsatellite instability-based testing [with or without mutL homologue 1 (MLH1) promoter hypermethylation testing], with Lynch syndrome diagnosis being established though germline testing of normal (non-tumour) tissue for constitutional mutations in mismatch repair. The risk of bias in studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, the Consolidated Health Economic Reporting Standards and the Philips' checklist. Two reviewers independently conducted each stage of the review. A meta-analysis of test accuracy was not possible because of the number and heterogeneity of studies. A narrative summary of test accuracy results was provided, reporting test accuracy estimates and presenting forest plots. The economic model constituted a decision tree followed by Markov models for the impact of colorectal and endometrial surveillance, and aspirin prophylaxis with a lifetime time horizon. RESULTS: The clinical effectiveness search identified 3308 studies; 38 studies of test accuracy were included. (No studies of clinical effectiveness of endometrial cancer surveillance met the inclusion criteria.) Four test accuracy studies compared microsatellite instability with immunohistochemistry. No clear difference in accuracy between immunohistochemistry and microsatellite instability was observed. There was some evidence that specificity of immunohistochemistry could be improved with the addition of methylation testing. There was high concordance between immunohistochemistry and microsatellite instability. The economic model indicated that all testing strategies, compared with no testing, were cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Immunohistochemistry with MLH1 promoter hypermethylation testing was the most cost-effective strategy, with an incremental cost-effectiveness ratio of £9420 per quality-adjusted life-year. The second most cost-effective strategy was immunohistochemistry testing alone, but incremental analysis produced an incremental cost-effectiveness ratio exceeding £130,000. Results were robust across all scenario analyses. Incremental cost-effectiveness ratios ranged from £5690 to £20,740; only removing the benefits of colorectal cancer surveillance produced an incremental cost-effectiveness ratio in excess of the £20,000 willingness-to-pay threshold. A sensitivity analysis identified the main cost drivers of the incremental cost-effectiveness ratio as percentage of relatives accepting counselling and prevalence of Lynch syndrome in the population. A probabilistic sensitivity analysis showed, at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year, a 0.93 probability that immunohistochemistry with MLH1 promoter hypermethylation testing is cost-effective, compared with no testing. LIMITATIONS: The systematic review excluded grey literature, studies written in non-English languages and studies for which the reference standard could not be established. Studies were included when Lynch syndrome was diagnosed by genetic confirmation of constitutional variants in the four mismatch repair genes (i.e. MLH1, mutS homologue 2, mutS homologue 6 and postmeiotic segregation increased 2). Variants of uncertain significance were reported as per the studies. There were limitations in the economic model around uncertainty in the model parameters and a lack of modelling of the potential harms of gynaecological surveillance and specific pathway modelling of genetic testing for somatic mismatch repair mutations. CONCLUSION: The economic model suggests that testing women with endometrial cancer for Lynch syndrome is cost-effective, but that results should be treated with caution because of uncertain model inputs. FUTURE WORK: Randomised controlled trials could provide evidence on the effect of earlier intervention on outcomes and the balance of benefits and harms of gynaecological cancer surveillance. Follow-up of negative cases through disease registers could be used to determine false negative cases. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019147185. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 42. See the NIHR Journals Library website for further project information.

Lynch syndrome is an inherited condition that is caused by a problem in the genes. People who have Lynch syndrome have a higher risk of some types of cancer (such as bowel and womb cancers) than people who do not have it. Identifying Lynch syndrome could stop cancers developing, lead to earlier treatment for cancers and help to find other family members who might have it. Currently, the National Institute for Health and Care Excellence guidance recommends testing for Lynch syndrome in people who have bowel cancer. Our aim was to investigate whether or not we should test for Lynch syndrome in women with womb cancer, and their relatives. We investigated two main tests: immunohistochemistry and microsatellite instability. There was no clear evidence that one of these tests is better than the other. There is some evidence that both tests are reasonably accurate. There was no good-quality evidence about whether or not treating women with Lynch syndrome with extra cancer screening and aspirin improves their outcomes. We used the best evidence available in our economic model, but it was at high risk of bias. The economic model suggested that testing women with endometrial cancer for Lynch syndrome is cost-effective. The best test in the model was immunohistochemistry followed by methylation testing. We are unsure of these results because of the low quality of evidence available.

A systematic review of economic evaluations for donor human milk versus standard feeding in infants.

Reviews on the cost/outcome of donor human milk (DHM) for infants requiring care in the neonatal intensive care unit (NICU) setting have been undertaken. However, the cost-effectiveness evidence is unclear. Therefore, we conducted a systematic review of published full economic evaluations of DHM versus standard feeding in infants in neonatal care with the aim of undertaking a narrative synthesis of the cost-effectiveness evidence and critical appraisal of the methods used. MEDLINE, EMBASE, Web of Science, Cochrane Library, Centre for Reviews and Dissemination (CRD) and PROSPERO databases were searched. Studies were included if they were full economic evaluations (model-based or trial-based), the participants were infants in neonatal units requiring nutritional support, the intervention was DHM and the comparator was any standard feeding option. There were no restrictions on outcome measures. Two authors independently assessed eligibility, extracted data, assessed quality and cross-checked results, with disagreements resolved by consensus. Information extracted focused on study context, and economic evaluation methods and results. Of 2861 studies, seven were included. Six (86%) studies originated from high-income countries. Four (57%) of the studies were model-based. Although we could not directly compare the different studies, due to the heterogenous nature of health and economic parameters used in the studies, all DHM interventions indicated cost-effective or cost saving results. This review suggests that economic evaluation of DHM interventions is an expanding area of research. Although these interventions show promise, future economic evaluations of DHM interventions need to explicitly provide more details on long-term costs and consequences.