The PHEM-B toolbox of methods for incorporating the influences on Behaviour into Public Health Economic Models.

BACKGROUND: It is challenging to predict long-term outcomes of interventions without understanding how they work. Health economic models of public health interventions often do not incorporate the many determinants of individual and population behaviours that influence long term effectiveness. The aim of this paper is to draw on psychology, sociology, behavioural economics, complexity science and health economics to: (a) develop a toolbox of methods for incorporating the influences on behaviour into public health economic models (PHEM-B); and (b) set out a research agenda for health economic modellers and behavioural/ social scientists to further advance methods to better inform public health policy decisions. METHODS: A core multidisciplinary group developed a preliminary toolbox from a published review of the literature and tested this conceptually using a case study of a diabetes prevention simulation. The core group was augmented by a much wider group that covered a broader range of multidisciplinary expertise. We used a consensus method to gain agreement of the PHEM-B toolbox. This included a one-day workshop and subsequent reviews of the toolbox. RESULTS: The PHEM-B toolbox sets out 12 methods which can be used in different combinations to incorporate influences on behaviours into public health economic models: collaborations between modellers and behavioural scientists, literature reviewing, application of the Behaviour Change Intervention Ontology, systems mapping, agent-based modelling, differential equation modelling, social network analysis, geographical information systems, discrete event simulation, theory-informed statistical and econometric analyses, expert elicitation, and qualitative research/process tracing. For each method, we provide a description with key references, an expert consensus on the circumstances when they could be used, and the resources required. CONCLUSIONS: This is the first attempt to rigorously and coherently propose methods to incorporate the influences on behaviour into health economic models of public health interventions. It may not always be feasible or necessary to model the influences on behaviour explicitly, but it is essential to develop an understanding of the key influences. Changing behaviour and maintaining that behaviour change could have different influences; thus, there could be benefits in modelling these separately. Future research is needed to develop, collaboratively with behavioural scientists, a suite of more robust health economic models of health-related behaviours, reported transparently, including coding, which would allow model reuse and adaptation.

Guidance on the use of complex systems models for economic evaluations of public health interventions.

To help health economic modelers respond to demands for greater use of complex systems models in public health. To propose identifiable features of such models and support researchers to plan public health modeling projects using these models. A working group of experts in complex systems modeling and economic evaluation was brought together to develop and jointly write guidance for the use of complex systems models for health economic analysis. The content of workshops was informed by a scoping review. A public health complex systems model for economic evaluation is defined as a quantitative, dynamic, non-linear model that incorporates feedback and interactions among model elements, in order to capture emergent outcomes and estimate health, economic and potentially other consequences to inform public policies. The guidance covers: when complex systems modeling is needed; principles for designing a complex systems model; and how to choose an appropriate modeling technique. This paper provides a definition to identify and characterize complex systems models for economic evaluations and proposes guidance on key aspects of the process for health economics analysis. This document will support the development of complex systems models, with impact on public health systems policy and decision making.

Eco-evolutionary causes and consequences of rarity in plants: a meta-analysis.

Species differ dramatically in their prevalence in the natural world, with many species characterized as rare due to restricted geographic distribution, low local abundance and/or habitat specialization. We investigated the ecoevolutionary causes and consequences of rarity with phylogenetically controlled metaanalyses of population genetic diversity, fitness and functional traits in rare and common congeneric plant species. Our syntheses included 252 rare species and 267 common congeners reported in 153 peer-reviewed articles published from 1978 to 2020 and one manuscript in press. Rare species have reduced population genetic diversity, depressed fitness and smaller reproductive structures than common congeners. Rare species also could suffer from inbreeding depression and reduced fertilization efficiency. By limiting their capacity to adapt and migrate, these characteristics could influence contemporary patterns of rarity and increase the susceptibility of rare species to rapid environmental change. We recommend that future studies present more nuanced data on the extent of rarity in focal species, expose rare and common species to ecologically relevant treatments, including reciprocal transplants, and conduct quantitative genetic and population genomic analyses across a greater array of systems. This research could elucidate the processes that contribute to rarity and generate robust predictions of extinction risks under global change.

Adrenocortical Function in Children With Brain Tumors and Pediatric Hematopoietic Cell Transplantation Recipients.

Adrenocortical insufficiency (AI) is a clinical condition defined by deficient production of glucocorticoids that can result in life-threatening complications. We examined the prevalence of AI in children with brain tumors and those undergoing hematopoietic cell transplantation. Adrenocorticotropic hormone stimulation (stim) testing was used for the assessment of adrenocortical function. On the basis of 155 stim tests in 117 patients, AI was diagnosed in 27.4% of patients with brain tumors and in 21% of hematopoietic cell transplantation recipients. A number of risk factors associated with AI were identified. Adrenocorticotropic hormone stim testing led to a definitive diagnosis of AI or recovery of adrenal function and unambiguous medical management.

Treatment with High-Dose Prednisolone in Vigabatrin-Refractory Infantile Spasms.

OBJECTIVES: This research aimed to study the short-term seizure outcomes following treatment with 8 mg/kg/day prednisolone in children with infantile spasms (IS) refractory to vigabatrin. We hypothesized that high-dose prednisolone may result in similar rates of electroclinical remission when compared to published ACTH rates. METHODS: All consecutive children with hypsarrhythmia or hypsarrhythmia variant on EEG with/without IS, who had been treated with vigabatrin as first-line anti-seizure medication (ASM) followed by high-dose oral prednisolone (8 mg/kg/day; maximum 60 mg/day) in cases who did not respond to vigabatrin, were included. Clinical and electroclinical response (ECR) at 2 weeks following initiation of treatment and adverse effects were assessed. RESULTS: Sixty-five children were included. A genetic etiology was seen in 38.5% cases. Complete ECR was seen in 30.8% (20/65) of the patients 2 weeks after vigabatrin. Complete ECR was noted in 77.8% (35/45) of the patients, 2 weeks after prednisolone initiation in children who failed vigabatrin, and this was sustained at 6 weeks in 66.7% (30/45) patients. Prednisolone was generally well tolerated. CONCLUSIONS: High-dose (8 mg/kg/day) oral prednisolone resulted in sustained complete ECR (at 6 weeks) in two-thirds of the children with hypsarrhythmia or hypsarrhythmia variant on EEG with/without parentally reported IS. It was generally well tolerated and found to be safe.

Newborn Screening for Spinal Muscular Atrophy: Ontario Testing and Follow-up Recommendations.

BACKGROUND: Spinal muscular atrophy (SMA) is characterized by the progressive loss of motor neurons causing muscle atrophy and weakness. Nusinersen, the first effective SMA therapy was approved by Health Canada in June 2017 and has been added to the provincial formulary of all but one Canadian province. Access to this effective therapy has triggered the inclusion of SMA in an increasing number of Newborn Screening (NBS) programs. However, the range of disease-modifying SMN2 gene copy numbers encountered in survival motor neuron 1 (SMN1)-null individuals means that neither screen-positive definition nor resulting treatment decisions can be determined by SMN1 genotype alone. We outline an approach to this challenge, one that specifically addresses the case of SMA newborns with four copies of SMN2. OBJECTIVES: To develop a standardized post-referral evaluation pathway for babies with a positive SMA NBS screen result. METHODS: An SMA NBS pilot trial in Ontario using first-tier MassARRAY and second-tier multi-ligand probe amplification (MLPA) was launched in January 2020. Prior to this, Ontario pediatric neuromuscular disease and NBS experts met to review the evidence regarding the diagnosis and treatment of children with SMA as it pertained to NBS. A post-referral evaluation algorithm was developed, outlining timelines for patient retrieval and management. CONCLUSIONS: Ontario's pilot NBS program has created a standardized path to facilitate early diagnosis of SMA and initiation of treatment. The goal is to provide timely access to those SMA infants in need of therapy to optimize motor function and prolong survival.

The impact of disinvestment on alcohol and drug treatment delivery and outcomes: a systematic review.

BACKGROUND: In the context of substantial financial disinvestment from alcohol and drug treatment services in England, our aim was to review the existing evidence of how such disinvestments have impacted service delivery, uptake, outcomes and broader health and social implications. METHODS: We conducted a systematic review of quantitative and qualitative evidence (PROSPERO CRD42020187295), searching bibliographic databases and grey literature. Given that an initial scoping search highlighted a scarcity of evidence specific to substance use treatment, evidence of disinvestment from publicly funded sexual health and smoking cessation services was also included. Data on disinvestment, political contexts and impacts were extracted, analysed, and synthesized thematically. RESULTS: We found 20 eligible papers varying in design and quality including 10 related to alcohol and drugs services, and 10 to broader public health services. The literature provides evidence of sustained disinvestment from alcohol and drug treatment in several countries and a concurrent decline in the quantity and quality of treatment provision, but there was a lack of methodologically rigorous studies investigating the impact of disinvestment. CONCLUSIONS: This review identified a paucity of scientific evidence quantifying the impacts of disinvestment on alcohol and drug treatment service delivery and outcomes. As the global economy faces new challenges, a stronger evidence base would enable informed policy decisions that consider the likely public health impacts of continued disinvestment.

Clustering of health-related behaviours within children aged 11-16: a systematic review.

OBJECTIVE: We aimed to systematically review and synthesise evidence on the clustering of a broad range of health-related behaviours amongst 11-16 year olds. METHOD: A literature search was conducted in September 2019. Studies were included if they used cluster analysis, latent class analysis, prevalence odds ratios, principal component analysis or factor analysis, and considered at least three health-related behaviours of interest among 11-16 year olds in high-income countries. Health-related behaviours of interest were substance use (alcohol, cigarettes and other drug use) and other behavioural risk indicators (diet, physical activity, gambling and sexual activity). RESULTS: The review identified 41 studies, which reported 198 clusters of health-related behaviours of interest. The behaviours of interest reported within clusters were used to define eight behavioural archetypes. Some included studies only explored substance use, while others considered substance use and/or other health-related behaviours. Consequently, three archetypes were comprised by clusters reporting substance use behaviours alone. The archetypes were: (1) Poly-Substance Users, (2) Single Substance Users, (3) Substance Abstainers, (4) Substance Users with No/Low Behavioural Risk Indicators, (5) Substance Abstainers with Behavioural Risk Indicators, (6) Complex Configurations, (7) Overall Unhealthy and (8) Overall Healthy. CONCLUSION: Studies of youth health behavioural clustering typically find both a 'healthy' cluster and an 'unhealthy' cluster. Unhealthy clusters are often characterised by poly-substance use. Our approach to synthesising cluster analyses may offer a means of navigating the heterogeneity of method, measures and behaviours of interest in this literature.

The Effect of Psychoeducation on Internalized Stigma of the Hospitalized Patients with Bipolar Disorder: A Quasi-Experimental Study.

Stigma is one of the common problems of patients with bipolar disorders, which impedes their recovery. This is a quasi-experimental study on 76 hospitalized patients with bipolar disorder (38 in each group) in Iran. The intervention group received six sessions of psychoeducation in a period of 2 weeks. Internalized stigma was measured by the Internalized Stigma of Mental Illness scale. The education significantly reduced the scores of alienation, discrimination experience, stigma resistance and total score of stigma in the intervention group. Hence, this education can be used as an accessible technique in hospitals to reduce the internalized stigma.

Developing Organizational Interventions to Address Stigma Among Mental Health Providers: A Pilot Study.

This article outlines a pilot study of "It's Just Us," an organizational intervention designed to reduce stigma among mental health providers by increasing awareness of the stigma they hold toward both clients and other providers with lived experience of mental health challenges. The targeted organization was the Mental Health Service Line in a large, Midwestern VA health care system. About 30% of the clinicians in the service provided information about their levels of stigma toward clients and providers who manage mental health challenges at baseline, 1 year later, and 2 years later. Educational and contact interventions targeting stigma are detailed; the first year included education and short-term contact interventions, while the second year included continuous contact interventions. At the end of the first year, scores on a measure of stigma toward mental health providers with lived experience were significantly lower, while scores on (a) a self-report measure of stigma toward clients and (b) self-disclosure of lived experience to professional peers were unchanged. At the end of the second year, scores for stigma toward clients had improved, and providers in the sample were more likely to share their lived experience with professional peers. Further research is necessary to validate these findings. Data provides preliminary support for the use of the "It's Just Us" curriculum as a means of reducing stigma among mental health providers. This model may also be useful in addressing stigma among other types of health care providers as well.

Healthcare provider perceptions of the role of interprofessional care in access to and outcomes of primary care in an underserved area.

To meet the needs of an aging population who often have multiple chronic conditions, interprofessional care is increasingly adopted by patient-centred medical homes and Accountable Care Organisations to improve patient care coordination and decrease costs in the United States, especially in underserved areas with primary care workforce shortages. In this cross-sectional survey across multiple clinical settings in an underserved area, healthcare providers perceived overall outcomes associated with interprofessional care teams as positive. This included healthcare providers' beliefs that interprofessional care teams improved patient outcomes, increased clinic efficiency, and enhanced care coordination and patient follow-up. Teams with primary care physician available each day were perceived as better able to coordinate care and follow up with patients (p = .031), while teams that included clinical pharmacists were perceived as preventing medication-associated problems (p < .0001). Healthcare providers perceived the interprofessional care model as a useful strategy to improve various outcomes across different clinical settings in the context of a shortage of primary care physicians.

Economic models for sustainable interprofessional education.

Limited information exists on funding models for interprofessional education (IPE) course delivery, even though potential savings from IPE could be gained in healthcare delivery efficiencies and patient safety. Unanticipated economic barriers to implementing an IPE curriculum across programs and schools in University settings can stymie or even end movement toward collaboration and sustainable culture change. Clarity among stakeholders, including institutional leadership, faculty, and students, is necessary to avoid confusion about IPE tuition costs and funds flow, given that IPE involves multiple schools and programs sharing space, time, faculty, and tuition dollars. In this paper, we consider three funding models for IPE: (a) Centralized (b) Blended, and (c) Decentralized. The strengths and challenges associated with each of these models are discussed. Beginning such a discussion will move us toward understanding the return on investment of IPE.

Recipient Immune Modulation with Atorvastatin for Acute Graft-versus-Host Disease Prophylaxis after Allogeneic Transplantation.

Atorvastatin administration to both the donors and recipients of matched related donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute graft-versus-host disease (GVHD) prophylaxis has been shown to be safe and effective. However, its efficacy as acute GVHD prophylaxis when given only to allo-HCT recipients is unknown. We conducted a phase II study to evaluate the safety and efficacy of atorvastatin-based acute GVHD prophylaxis given only to the recipients of MRD (n = 30) or matched unrelated donor (MUD) (n = 39) allo-HCT, enrolled in 2 separate cohorts. Atorvastatin (40 mg/day) was administered along with standard GVHD prophylaxis consisting of tacrolimus and methotrexate. All patients were evaluable for acute GVHD. The cumulative incidences of grade II to IV acute GVHD at day +100 in the MRD and MUD cohorts were 9.9% (95% confidence interval [CI], 0 to 20%) and 29.6% (95% CI,15.6% to 43.6%), respectively. The cumulative incidences of grade III and IV acute GVHD at day +100 in the MRD and MUD cohorts were 3.4% (95% CI, 0 to 9.7%) and 18.3% (95% CI, 6.3% to 30.4%), respectively. The corresponding rates of moderate/severe chronic GVHD at 1 year were 28.1% (95% CI, 11% to 45.2%) and 38.9% (95% CI, 20.9% to 57%), respectively. In the MRD cohort, the 1-year nonrelapse mortality, relapse rate, progression-free survival, and overall survival were 6.7% (95% CI, 0 to 15.4%), 43.3% (95% CI, 24.9% to 61.7%), 50% (95% CI, 32.1% to 67.9%), and 66.7% (95% CI, 49.8% to 83.6%), respectively. The respective figures for the MUD cohort were 10.3% (95% CI, 8% to 19.7%), 20.5% (95% CI, 7.9% to 33.1%), 69.2% (95% CI, 54.7% to 83.7%), and 79.5% (95% CI, 66.8% to 92.2%), respectively. No grade 4 toxicities attributable to atorvastatin were seen. In conclusion, the addition of atorvastatin to standard GVHD prophylaxis in only the recipients of MRD and MUD allo-HCT appears to be feasible and safe. The preliminary efficacy seen here warrants confirmation in randomized trials.

The Internalized Stigma of Mental Illness: Cross-Cultural Adaptation and Psychometric Properties of the Portuguese Version of the ISMI Scale.

This study examined the psychometric properties of the Portuguese version of the ISMI scale in a sample of 253 adult psychiatric outpatients. The exploratory factor analysis replicated the five factor structure of the scale. The results revealed good internal consistency. Criterion-related validity supported the variability in response to stigma across clinical diagnoses. Thus, the Portuguese version of the ISMI scale can be considered appropriate to measure and differentiate between stigmatization experiences. Also, in order to design more focused approaches aimed to reduce the negative effects of internalized stigma, its use in institutional and in community-based mental health services is recommended.

How safe is renal replacement therapy? A national study of mortality and adverse events contributing to the death of renal replacement therapy recipients.

BACKGROUND: Patients receiving treatment with renal replacement therapy (RRT) have high mortality, and ensuring patient safety in this population is difficult. We aimed to estimate the incidence and nature of medical adverse events contributing to the death of patients being treated with RRT. METHODS: This population registry-based retrospective case review study included all patients being treated with RRT for established renal failure in Scotland and who died between 1 January 2008 and 30 June 2011. Deaths were reviewed by consultant nephrologists using a structured questionnaire to identify factors contributing to death occurring in both the inpatient and outpatient setting. Reviewers were able to use any information source deemed relevant, including paper and electronic clinical records, mortality and morbidity meetings and procurator fiscal (Scottish coroner) investigations. Deaths occurring in 2008 and 2009 where avoidable factors were identified that may have or did lead to death of a patient were subject to further review and root cause analysis, in order to identify recurrent themes. RESULTS: Of 1551 deaths in the study period, 1357 were reviewed (87.5%). Cumulative RRT exposure in the cohort was 2.78 million person-days. RRT complications were the primary cause of death in 28 (2.1%). Health-care-associated infection had contributed to 9.6% of all deaths. In 3.5% of deaths, factors were identified which may have or did contribute to death. These were both organizational and human error related and were largely due to five main causes: management of hyperkalaemia, prescribing, out of hours care, infection and haemodialysis vascular access. CONCLUSIONS: Adverse events contributing to death in RRT recipients mainly relate to the everyday management of common medical problems and not the technical aspects of RRT. Efforts to avoid harm in this population should address these ubiquitous causes of harm.

Internalized Stigma of Mental Illness (ISMI) scale: a multinational review.

The Internalized Stigma of Mental Illness (ISMI) scale is a 29-item questionnaire measuring self-stigma among persons with psychiatric disorders. It was developed with substantial consumer input and has been widely used, but its psychometric qualities have not been comprehensively evaluated across multiple versions. Here we review the 55 known versions, and provide the 47 available versions, including: Arabic, Armenian, Bengali, Bulgarian, Chinese (Mainland, Taiwan, Hong Kong), Croatian, Dutch, English (USA, South Africa), Estonian, Farsi, Finnish, French, German, Greek, Hebrew, Hindi, Japanese, Khmer, Korean, Lithuanian, Lugandan, Maltese, Polish, Portuguese (Portugal, Brazil), Romanian, Russian, Samoan, Slovenian, Spanish (Spain), Swahili, Swedish, Tongan, Turkish, Urdu, and Yoruba, and qualitative English and Swahili versions, as well as versions for depression, schizophrenia, substance abuse, eating disorders, epilepsy, inflammatory bowel disease, leprosy, smoking, parents and caregivers of people with mental illness, and ethnicity. The various versions show reliability and validity across a wide range of languages, cultures, and writing systems. The most commonly reported findings of studies using the ISMI are that internalized stigma correlates with higher depression, lower self esteem, and higher symptom severity. Initial studies of ways to reduce internalized stigma are promising and warrant further investigation.

Access to MAT: Participants' Experiences With Transportation, Non-Emergency Transportation, and Telehealth.

INTRODUCTION: Access to medication assisted treatment (MAT) for opioid use disorder (OUD) in the United States is a significant challenge for many individuals attempting to recover and improve their lives. Access to treatment is especially challenging in rural areas characterized by lack of programs, few prescribers, and transportation barriers. This study aims to better understand the roles that transportation, Medicaid-funded non-emergency medical transportation (NEMT), and telehealth play in facilitating access to MAT in West Virginia (WV). METHODS: We developed this survey using an exploratory sequential mixed methods approach following a review of current peer-reviewed literature plus information gained from 3 semi-structured interviews and follow-up discussions with 5 individuals with lived experience in MAT. Survey results from 225 individuals provided rich context on the influence of transportation in enrolling and remaining in treatment, use of NEMT, and experiences using telehealth. Data were collected from February through August 2021. RESULTS: We found that transportation is a significant factor in entering into and remaining in treatment, with 170 (75.9%) respondents agreeing or strongly agreeing that having transportation was a factor in deciding to go into a MAT program, and 176 (71.1%) agreeing or strongly agreeing that having transportation helps them stay in treatment. NEMT was used by one-quarter (n = 52, 25.7%) of respondents. Only 13 (27.1%) noted that they were picked up on time and only 14 (29.2%) noted that it got them to their appointment on time. Two thirds of respondents (n = 134, 66.3%) had participated in MAT services via telehealth video or telephone visits. More preferred in-person visits to telehealth visits but a substantial number either preferred telehealth or reported no preference. However, 18 (13.6%) reported various challenges in using telehealth. CONCLUSIONS: This study confirms that transportation plays a significant role in many people's decisions to enter and remain in treatment for OUD in WV. Additionally, for those who rely on NEMT, services can be unreliable. Finally, findings demonstrate the need for individualized care and options for accessing treatment for OUD in both in-person and telehealth-based modalities. Programs and payers should examine all possible options to ensure access to care and recovery.

How can agent-based modelling provide new insights into the impact of minimum unit pricing in Scotland?

In recent years we have gained insight into the impact of minimum unit pricing (MUP)-a legal floor price below which a given volume of alcohol cannot be sold-on population-level reductions in alcohol sales, consumption and harm. However, several questions remain unanswered including how individual-level purchasing changes impact the local economy (e.g., balance between on-licence and off-licence outlets), lead to long-term population-level trends (e.g., youth drinking) and social harms (e.g., violence). Agent-based modelling captures heterogeneity, emergence, feedback loops and adaptive and dynamic features, which provides an opportunity to understand the nuanced effects of MUP. Agent-based models (ABM) simulate heterogeneous agents (e.g., individuals, organisations) often situated in space and time that interact with other agents and/or with their environment, allowing us to identify the mechanisms underlying social phenomena. ABMs are particularly useful for theory development, and testing and simulating the impacts of policies and interventions. We illustrate how ABMs could be applied to generate novel insights and provide best estimates of social network effects, and changes in purchasing behaviour and social harms, due to the implementation of MUP. ABMs like other modelling approaches can simulate alternative implementations of MUP (e.g., policy intensity [£0.50, £0.60] or spatial scales [local, national]) but can also provide an understanding of the potential impact of MUP on different population groups (e.g., alcohol exposure of young people who are not yet drinking). Using ABMs to understand the impact of MUP would provide new insights to complement those from traditional epidemiological and other modelling methods.

The impact of Scotland's minimum unit pricing for alcohol policy on people accessing services for alcohol dependence: A difference-in-difference structured interview study.

INTRODUCTION: A minimum unit price (MUP) for alcohol of £0.50 per unit (1 UK unit = 10 mL/8 g alcohol) was introduced in Scotland in May 2018. Few previous studies have examined the impact of alcohol pricing policies on people who are alcohol dependent. This study aimed to evaluate the effect of MUP on people who are alcohol dependent including changes in alcohol consumption and health status, as well as potential unintended consequences. METHODS: Three waves of cross-sectional data were collected in Scotland (intervention) and Northern England (control) at 0-6 months pre-implementation then 3-9 months and 18-22 months post-implementation. The sample was N = 706 people receiving treatment related to their alcohol use. We collected structured interview data including recent drinking information via a 7-day timeline-follow-back drinking diary. Difference-in-difference analyses estimated change in indicators in Scotland compared to England at both post-implementation timepoints. RESULTS: The proportion of participants consuming alcohol costing on average <£0.50 per unit in Scotland decreased from 60.6% at 0-6 months prior to MUP implementation to 6.3% at 3-9 months post-implementation (p < 0.0004). There was no significant change in the indicators for alcohol consumption, severity of dependence, health status, other substance use, deprivation level or parenting. DISCUSSION AND CONCLUSIONS: The introduction of MUP in Scotland was associated with increases in the prices paid for alcohol by people with dependence and presenting to treatment services. There was no evidence of changes in their alcohol consumption or health status. There was also no evidence of harmful unintended consequences for this population.