A library of logic models to explain how interventions to reduce diagnostic error work

OBJECTIVES: We aimed to create a library of logic models for interventions to reduce diagnostic error. This library can be used by those developing, implementing, or evaluating an intervention to improve patient care, to understand what needs to happen, and in what order, if the intervention is to be effective. METHODS: To create the library, we modified an existing method for generating logic models. The following five ordered activities to include in each model were defined: preintervention; implementation of the intervention; postimplementation, but before the immediate outcome can occur; the immediate outcome (usually behavior change); and postimmediate outcome, but before a reduction in diagnostic errors can occur. We also included reasons for lack of progress through the model. Relevant information was extracted about existing evaluations of interventions to reduce diagnostic error, identified by updating a previous systematic review. RESULTS: Data were synthesized to create logic models for four types of intervention, addressing five causes of diagnostic error in seven stages in the diagnostic pathway. In total, 46 interventions from 43 studies were included and 24 different logic models were generated. CONCLUSIONS: We used a novel approach to create a freely available library of logic models. The models highlight the importance of attending to what needs to occur before and after intervention delivery if the intervention is to be effective. Our work provides a useful starting point for intervention developers, helps evaluators identify intermediate outcomes, and provides a method to enable others to generate libraries for interventions targeting other errors

Parenting behaviors that shape child compliance: A multilevel meta-analysis

Background What are the parenting behaviors that shape child compliance? Most research on parent-child interactions relies on correlational research or evaluations of “package deal” interventions that manipulate many aspects of parenting at the same time. Neither approach allows for identifying the specific parenting behaviors that shape child compliance. To overcome this, we systematically reviewed and meta-analyzed available evidence on the effects of experimentally manipulated, discrete parenting behaviors—a niche in parent-child interaction research that contributes unique information on the specific parenting behaviors that shape child behavior. Methods We identified studies by systematically searching databases and through contacting experts. Nineteen studies (75 effect sizes) on four discrete parenting behaviors were included: praise, verbal reprimands, time-out, and ignore. In multilevel models, we tested for each parenting behavior whether it increased child compliance, including both observed and parent-reported measures of child compliance. Results Providing “time-out” for noncompliance robustly increased both observed and parent-reported child compliance (ds = 0.84–1.72; 95% CI 0.30 to 2.54). The same holds for briefly ignoring the child after non-compliance (ds = 0.36–1.77; 95% CI 0.04 to 2.90). When observed and parent-reported outcomes were combined, but not when they were examined separately, verbal reprimands also increased child compliance (d = 0.72; 95% CI 0.26 to 1.19). Praise did not increase child compliance (ds = –0.27–1.19; 95% CI –2.04 to 1.59). Conclusion Our findings suggest that of the discrete parenting behaviors that are experimentally studied in multiple trials, especially time-out and ignore, and to some extent verbal reprimands, shape child compliance

Ixazomib for relapsed or refractory multiple myeloma : review from an evidence review group on a NICE single technology appraisal

Ixazomib is an oral proteasome inhibitor used in combination with lenalidomide plus dexamethasone (IXA-LEN-DEX) and licensed for relapsed or refractory multiple myeloma. As part of a single technology appraisal (ID807) undertaken by the National Institute of Health and Care Excellence, the Evidence Review Group, Warwick Evidence was invited to independently review the evidence submitted by the manufacturer of ixazomib, Takeda UK Ltd. The main source of clinical effectiveness data about IXA-LEN-DEX came from the Tourmaline-MM1 randomized controlled trial in which 771 patients with relapsed or refractory multiple myeloma received either IXA-LEN-DEX or placebo-LEN-DEX as their second-, third-, or fourth-line treatment. Takeda estimated the cost effectiveness of IXA-LEN-DEX using a de-novo partitioned-survival model with three health states (pre-progression, post-progression, and dead). In their first submission, this model was used to estimate the cost effectiveness of IXA-LEN-DEX vs. bortezomib plus dexamethasone (BORT-DEX) in second-line treatment, and of IXA-LEN-DEX vs. LEN-DEX in third-line treatment. To estimate the relative clinical performance of IXA-LEN-DEX vs. BORT-DEX, Takeda conducted network meta-analyses for important outcomes. The network meta-analysis for overall survival was found to be flawed in several respects, but mainly because a hazard ratio input for one of the studies in the network had been inverted, resulting in a large inflation of the claimed superiority of IXA-LEN-DEX over BORT-DEX and a considerable overestimation of its cost effectiveness. In subsequent submissions, Takeda withdrew second-line treatment as an option for IXA-LEN-DEX. The manufacturer’s first submission comparing IXA-LEN-DEX with LEN-DEX for third-line therapy employed Tourmaline-MM1 data from third- and fourth-line patients as proxy for a third-line population. The appraisal committee did not consider this reasonable because randomization in Tourmaline-MM1 was stratified according to one previous treatment and two or more previous treatments. A further deficiency was considered to be the manufacturer’s use of interim survival data rather than the most mature data available. A second submission from the company focussed on IXA-LEN-DEX vs. LEN-DEX as third- or fourth-line treatment (the two or more previous lines population) and a new patient access scheme was introduced. Covariate modeling of survival outcomes was proposed using the most mature survival data. The Evidence Review Group’s main criticisms of the new evidence included: the utility associated with the pre-progression health state was overestimated, treatment costs of ixazomib were underestimated, survival models were still associated with great uncertainty, leading to clinically implausible anomalies and highly variable incremental cost-effectiveness ratio estimates, and the company had not explored a strong assumption that the survival benefit of IXA-LEN-DEX over LEN-DEX would be fully maintained for a further 22 years beyond the observed data, which encompassed only approximately 2.5 years of observation. The appraisal committee remained unconvinced that ixazomib represented a cost-effective use of National Health Service resources. Takeda’s third submission offered new base-case parametric models for survival outcomes, a new analysis of utilities, and proposed a commercial access agreement. In a brief critique of the third submission, the Evidence Review Group agreed that the selection of appropriate survival models was problematic and at the request of the National Institute for Health Care and Excellence investigated external sources of evidence regarding survival outcomes. The Evidence Review Group considered that some cost and utility estimates in the submission may have remained biased in favor of ixazomib. As a result of their third appraisal meeting, the committee judged that for the two to three prior therapies population, and at the price agreed in a commercial access agreement, ixazomib had the potential to be cost effective. It was referred to the Cancer Drugs Fund so that further data could accrue with the aim of diminishing the clinical uncertainties

Exploring the association between school-based peer networks and smoking according to socioeconomic status and tobacco control context:a systematic review

BACKGROUND: Whilst prevalence of youth smoking in middle and high income countries has decreased, inequality has prevailed. The introduction of legislation regulating tobacco use in public spaces varies across countries, impacting the tobacco control context. Thus reviewing our knowledge of how social networks may influence smoking differently within different contexts is required to facilitate the development of context-specific interventions. METHODS: The search, conducted on 31st May 2019, included the following smoking-related terms; schools, adolescents, peers and social networks. Inclusion and exclusion criteria were applied throughout the title and abstract screening and full text screening. Quality assessment and synthesis followed. Studies were narratively synthesised to identify changes according to legislative context. This synthesis was conducted separately for findings relating to three categories: socioeconomic status; social selection and influence; and network position. RESULTS: Thirty studies were included. Differences in the relationship between network characteristics and smoking according to socioeconomic status were measured in five out of fifteen studies in Europe. Results varied across studies, with differences in network characteristics and their association with smoking varying both between schools of a differing and those of a similar socioeconomic composition. For studies conducted both before and after the introduction of comprehensive smoking legislation, the evidence for selection processes was more consistent than influence, which varied according to reciprocity. Findings showed that isolates were more likely to smoke and in-degree and out-degree centrality were related to smoking both before and after the introduction of legislation. The relationship between popularity and smoking was contingent on school level smoking prevalence in studies conducted before the introduction of legislation, but not after. CONCLUSIONS: Overall, effects according to socioeconomic status were underreported in the included studies and no consistent evidence of change after the introduction of a comprehensive smoking ban was observed. Further network analyses are required using more recent data to obtain a comprehensive understanding of how network processes may influence smoking differently according to socioeconomic status, and how adaptation could be used to enhance intervention effectiveness. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42019137358. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-12333-z

Co-occurring change in children's conduct problems and maternal depression: Latent class individual participant data meta-analysis of the Incredible Years parenting program

Children vary in the extent to which they benefit from parenting programs for conduct problems. How does parental mental health change if children benefit less or more? We assessed whether changes in conduct problems and maternal depressive symptoms co-occur following participation in the Incredible Years parenting program. We integrated individual participant data from 10 randomized trials (N = 1280; children aged 2–10 years) and distinguished latent classes based on families’ baseline and post-test conduct problems and maternal depressive symptoms, using repeated measures latent class analysis (RMLCA) and latent transition analysis (LTA). Classes differed mainly in severity of conduct problems and depression (RMLCA; 4 classes). Conduct problems reduced in all classes. Depressive symptoms did not change in most classes, except in a class of families where conduct problems and depression were particularly severe. Incredible Years led to a greater likelihood of families with particularly severe conduct problems and depression moving to a class with mild problems (LTA; 3 classes). Our findings suggest that for the majority of families, children’s conduct problems reduce, but maternal depressive symptoms do not, suggesting relative independence, with the exception of families with severe depression and severe conduct problems where changes for the better do co-occur

How effective are brief interventions in reducing alcohol consumption::do the setting, practitioner group and content matter? Findings from a systematic review and metaregression analysis

Background: While the efficacy and effectiveness of brief interventions for alcohol (ABI) have been demonstrated in primary care, there is weaker evidence in other settings and reviews do not consider differences in content. We conducted a systematic review to measure the effect of ABIs on alcohol consumption and how it differs by the setting, practitioner group and content of intervention. Methods: We searched MEDLINE, EMBASE, PsycINFO; CINAHL, Social Science Citation Index, Cochrane Library and Global Health up to January 2015 for randomised controlled trials that measured effectiveness of ABIs on alcohol consumption. We grouped outcomes into measures of quantity and frequency indices. We used multilevel meta-analysis to estimate pooled effect sizes and tested for the effect of moderators through a multiparameter Wald test. Stratified analysis of a subset of quantity and frequency outcomes was conducted as a sensitivity check. Results: 52 trials were included contributing data on 29 891 individuals. ABIs reduced the quantity of alcohol consumed by 0.15 SDs. While neither the setting nor content appeared to significantly moderate intervention effectiveness, the provider did in some analyses. Interventions delivered by nurses had the most effect in reducing quantity (d=−0.23, 95% CI (−0.33 to −0.13)) but not frequency of alcohol consumption. All content groups had statistically significant mean effects, brief advice was the most effective in reducing quantity consumed (d=−0.20, 95% CI (−0.30 to −0.09)). Effects were maintained in the stratified sensitivity analysis at the first and last assessment time. Conclusions: ABIs play a small but significant role in reducing alcohol consumption. Findings show the positive role of nurses in delivering interventions. The lack of evidence on the impact of content of intervention r

An initial typology of contexts of dyadic sexual encounters between men and associations with sexual risk and pleasure: findings from an observational study

Background: Although many within-subjects comparisons conducted on samples of men who have sex with men have sought to understand the association between specific situational characteristics (e.g. drug use or location of sex) and sexual risk behaviour, none have considered the ‘clustering’ of patterns of situational characteristics. An initial typology of sexual encounters is derived and the relationship of this typology to condomless anal intercourse (CAI) and pleasure is tested. Methods: Data from a longitudinal survey of men who have sex with men living in England were used. Multilevel latent class analyses were estimated to determine an optimal class solution on the situational characteristics, and then pseudo-imputation was used to estimate the association between class and both CAI and pleasure. Results: A three-class solution fit the data best, with a scaled relative entropy of 92.4%. Classes were characterised as featuring: regular steady partners in private locations with low drug use (class 1), casual partners with increased probability of sex occurring in a sex-on-premises venue (class 2), and high levels of polydrug use together with increased probability of casual partners (class 3). Encounters were different both in pairwise comparisons and overall on probability of CAI. They were different overall but not necessarily pairwise on pleasure. Conclusions: These initial findings demonstrate the possibility of understanding sexual encounters in terms of the contexts, or classes, within which they occur. This may have implications for tailoring HIV prevention to specific encounter types. Future research should seek to extend encounter-level typologies to specific drug use variables

Short and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome : a systematic review of randomised controlled trials and network meta-analysis

Source of funding: This work is part of a larger report commissioned by the NIHR HTA Programme as project number ID809. A.C. and G.J.M.T. are partly supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care West Midlands at the University Hospitals Birmingham NHS Foundation Trust.Peer reviewedPublisher PD

Does integrated academic and health education prevent substance use? Systematic review and meta-analyses

Background: Prevention of substance (alcohol, tobacco, illegal/legal drug) use in adolescents is a public health priority. As the scope for school ‐ based health education is constrained in school timetables, interventions integrating academic and health education have gained traction in the UK and elsewhere, though evidence for their effectiveness remains unclear. We sought to syn- thesize the effectiveness of interventions integrating academic and health education for the pre- vention of substance use. Methods: We searched 19 databases between November and December 2015, among other methods. We included randomized trials of interventions integrating academic and health educa- tion targeting school students aged 4 – 18 and reporting substance use outcomes. We excluded interventions for specific health ‐ related subpopulations (e.g., children with behavioural difficul- ties). Data were extracted independently in duplicate. Outcomes were synthesized by school key stage (KS) using multilevel meta ‐ analyses, for substance use, overall and by type. Results: We identified 7 trials reporting substance use. Interventions reduced substance use generally in years 7 – 9 (KS3) based on 5 evaluations ( d = − 0.09, 95% CI [ − 0.17, − 0.01], I 2 = 35%), as well as in years 10 – 11 (KS4) based on 3 evaluations ( − 0.06, [ − 0.09, − 0.02]; I 2 = 0%). Interventions were broadly effective for reducing specific alcohol, tobacco, and drug use in both KS groups. Conclusions: Evidence quality was highly variable. Findings for years 3 – 6 and 12 – 13 could not be meta ‐ analysed, and we could not assess publication bias. Interventions appear to have a small but significant effect reducing substance use. Specific methods of integrating academic and health education remain poorly understood