Akvile Stoniute

Background: Neonates with suspected sepsis are commonly treated with gentamicin, an aminoglycoside. These antibiotics are associated with high risk of ototoxicity, including profound bilateral deafness, in people with the m.1555A>G mitochondrial genetic variant. Objective: This early value assessment summarised and critically assessed the clinical effectiveness and cost-effectiveness of the Genedrive MT-RNR1 ID Kit for identifying the gene m.1555A>G variant in neonates and mothers of neonates needing antibiotics or anticipated to need antibiotics. Following feedback from the scoping workshop and specialist assessment subgroup meeting, we also considered the Genedrive MT-RNR1 ID Kit for identifying the m.1555A>G variant in mothers prior to giving birth. Data sources: For clinical effectiveness, we searched three major databases in October 2022: MEDLINE, EMBASE and CINAHL (Cumulative Index to Nursing and Allied Health Literature). For cost-effectiveness, in addition to the three mentioned databases we searched Cochrane and RePEc-IDEAS. Study selection: Study selection and risk-of-bias assessment were conducted by two independent reviewers (Ryan PW Kenny and Akvile Stoniute for clinical effectiveness and Hosein Shabaninejad and Tomos Robinson for cost-effectiveness). Any differences were resolved through discussion, or by a third reviewer (Nick Meader). Study appraisal: Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. One study (n = 751 neonates recruited) was included in the clinical effectiveness review and no studies were included in the cost-effectiveness review. All except one outcome (test failure rate: low risk of bias) were rated as being at moderate risk of bias. The study reported accuracy of the test (sensitivity 100%, 95% confidence interval 29.2% to 100%; specificity 99.2%, 95% confidence interval 98% to 99.7%), number of neonates successfully tested (n = 424/526 admissions), test failure rate (17.1%, although this was reduced to 5.7%), impact on antibiotic use (all those with a m.1555A>G genotype avoided aminoglycosides), time taken to obtain a sample (6 minutes), time to genotyping (26 minutes), time to antibiotic treatment (55.18 minutes) and the number of neonates with m.1555A>G (n = 3). Limitations: The economic component of this work identified key evidence gaps for which further data are required before a robust economic evaluation can be conducted. These include the sensitivity of the Genedrive MT-RNR1 ID Kit for identifying the gene m.1555A>G variant in neonates, the magnitude of risk for aminoglycoside-induced hearing loss in neonates with m.1555A>G, and the prevalence of the m.1555A>G variant. Other potentially important gaps include how data regarding maternal inheritance may potentially be used in the clinical pathway. Conclusions: This early value assessment suggests that the Genedrive MT-RNR1 ID Kit has the potential to identify the m.1555A>G variant and to be cost-effective. The Genedrive MT-RNR1 ID Kit dominates the current standard of care over the lifetime, as it is less costly and more effective. For a 50-year time horizon, the Genedrive MT-RNR1 ID Kit was also the dominant strategy. For a 10-year time horizon, the incremental cost-effectiveness ratio was estimated to be £103 per quality-adjusted life-year gained. Nevertheless, as anticipated, there is insufficient evidence to conduct a full diagnostic assessment of the clinical effectiveness and cost-effectiveness of the Genedrive MT-RNR1 ID Kit in neonates directly or in their mothers. This report includes a list of research priorities to reduce the uncertainty around this early value assessment and to provide the additional data needed to inform a full diagnostic assessment, including cost-effectiveness modelling. Study registration: This study is registered as PROSPERO (CRD42022364770). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR135636) and is published in full in Health Technology Assessment; Vol. 28, No. 75. See the NIHR Funding and Awards website for further award information.

Background: Early evidence suggests that using radiofrequency ablation as an adjunct to standard care (i.e. endoscopic retrograde cholangiopancreatography with stenting) may improve outcomes in patients with malignant biliary obstruction.Objectives: To assess the clinical effectiveness, cost-effectiveness and potential risks of endoscopic bipolar radiofrequency ablation for malignant biliary obstruction, and the value of future research.Data sources: Seven bibliographic databases, three websites and seven trials registers were searched from 2008 until 21 January 2021.Review methods: The study inclusion criteria were as follows: patients with biliary obstruction caused by any form of unresectable malignancy; the intervention was reported as an endoscopic biliary radiofrequency ablation to ablate malignant tissue that obstructs the bile or pancreatic ducts, either to fit a stent (primary radiofrequency ablation) or to clear an obstructed stent (secondary radiofrequency ablation); the primary outcomes were survival, quality of life or procedure-related adverse events; and the study design was a controlled study, an observational study or a case report. Risk of bias was assessed using Cochrane tools. The primary analysis was meta-analysis of the hazard ratio of mortality. Subgroup analyses were planned according to the type of probe, the type of stent (i.e. metal or plastic) and cancer type. A de novo Markov model was developed to model cost and quality-of-life outcomes associated with radiofrequency ablation in patients with primary advanced bile duct cancer. Insufficient data were available for pancreatic cancer and secondary bile duct cancer. An NHS and Personal Social Services perspective was adopted for the analysis. A probabilistic analysis was conducted to estimate the incremental cost-effectiveness ratio for radiofrequency ablation and the probability that radiofrequency ablation was cost-effective at different thresholds. The population expected value of perfect information was estimated in total and for the effectiveness parameters.Results: Sixty-eight studies (1742 patients) were included in the systematic review. Four studies (336 participants) were combined in a meta-analysis, which showed that the pooled hazard ratio for mortality following primary radiofrequency ablation compared with a stent-only control was 0.34 (95% confidence interval 0.21 to 0.55). Little evidence relating to the impact on quality of life was found. There was no evidence to suggest an increased risk of cholangitis or pancreatitis, but radiofrequency ablation may be associated with an increase in cholecystitis. The results of the cost-effectiveness analysis were that the costs of radiofrequency ablation was £2659 and radiofrequency ablation produced 0.18 quality-adjusted life-years, which was more than no radiofrequency ablation on average. With an incremental cost-effectiveness ratio of £14,392 per quality-adjusted life-year, radiofrequency ablation was likely to be cost-effective at a threshold of £20,000 per quality-adjusted life-year across most scenario analyses, with moderate uncertainty. The source of the vast majority of decision uncertainty lay in the effect of radiofrequency ablation on stent patency.Limitations: Only 6 of 18 comparative studies contributed to the survival meta-analysis, and few data were found concerning secondary radiofrequency ablation. The economic model and cost-effectiveness meta-analysis required simplification because of data limitations. Inconsistencies in standard reporting and study design were noted.Conclusions: Primary radiofrequency ablation increases survival and is likely to be cost-effective. The evidence for the impact of secondary radiofrequency ablation on survival and of quality of life is limited. There was a lack of robust clinical effectiveness data and, therefore, more information is needed for this indication.Future work: Future work investigating radiofrequency ablation must collect quality-of-life data. High-quality randomised controlled trials in secondary radiofrequency ablation are needed, with appropriate outcomes recorded.Study registration: This study is registered as PROSPERO CRD42020170233.Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 27, No. 7. See the NIHR Journals Library website for further project information.

Common mental health disorders (CMDs) disproportionately affect people experiencing socioeconomic disadvantage. Non-pharmaceutical interventions, such as ‘social prescribing’ and new models of care and clinical practice, are becoming increasingly prevalent in primary care. However, little is known about how these interventions work and their impact on socioeconomic inequalities in health. Focusing on people experiencing socioeconomic disadvantage, this systematic review aims to: (1) explore the mechanisms by which non-pharmaceutical primary care interventions impact CMD-related health outcomes and inequalities; (2) identify the barriers to, and facilitators of, their implementation in primary care. This study is a systematic review of qualitative studies. Six bibliographic databases were searched (Medline, ASSIA, CINAHL, Embase, PsycInfo and Scopus) and additional grey literature sources were screened. The included studies were thematically analysed. Twenty-two studies were included, and three themes were identified: (1) agency; (2) social connections; (3) socioeconomic environment. The interventions were experienced as being positive for mental health when people felt a sense of agency and social connection. The barriers to effectiveness and engagement included socioeconomic deprivation and underfunding of community sector organisations. If non-pharmaceutical primary care interventions for CMDs are to avoid widening health inequalities, key socioeconomic barriers to their accessibility and implementation must be addressed.

Background: Common mental health disorders are especially prevalent among people from socioeconomically disadvantaged backgrounds. Non-pharmaceutical primary care interventions, such as social prescribing and collaborative care, provide alternatives to pharmaceutical treatments for common mental health disorders, but little is known about the impact of these interventions for patients who are socioeconomically disadvantaged.Aim: To synthesise evidence for the effects of non-pharmaceutical primary care interventions on common mental health disorders and associated socioeconomic inequalities.Design and setting: Systematic review of quantitative primary studies published in English and undertaken in high-income countries.Method: Six bibliographic databases were searched and additional grey literature sources screened. Data were extracted onto a standardised proforma and quality assessed using the Effective Public Health Practice Project tool. Data were synthesised narratively and effect direction plots were produced for each outcome.Results: Thirteen studies were included. Social-prescribing interventions were evaluated in 10 studies, collaborative care in two studies, and a new model of care in one study. Positive results (based on effect direction) were reported for the impact of the interventions on wellbeing in groups that were socioeconomically deprived. Inconsistent (mainly positive) results were reported for anxiety and depression. One study reported that people from the group with least deprivation, compared with the group with greatest deprivation, benefitted most from these interventions. Overall, study quality was weak.Conclusion: Targeting non-pharmaceutical primary care interventions at areas of socioeconomic deprivation may help to reduce inequalities in mental health outcomes. However, only tentative conclusions can be drawn from the evidence in this review and more-robust research is required.