Mitigation strategies for pandemic influenza A: balancing conflicting policy objectives

Mitigation of a severe influenza pandemic can be achieved using a range of interventions to reduce transmission. Interventions can reduce the impact of an outbreak and buy time until vaccines are developed, but they may have high social and economic costs. The non-linear effect on the epidemic dynamics means that suitable strategies crucially depend on the precise aim of the intervention. National pandemic influenza plans rarely contain clear statements of policy objectives or prioritization of potentially conflicting aims, such as minimizing mortality (depending on the severity of a pandemic) or peak prevalence or limiting the socio-economic burden of contact-reducing interventions. We use epidemiological models of influenza A to investigate how contact-reducing interventions and availability of antiviral drugs or pre-pandemic vaccines contribute to achieving particular policy objectives. Our analyses show that the ideal strategy depends on the aim of an intervention and that the achievement of one policy objective may preclude success with others, e.g., constraining peak demand for public health resources may lengthen the duration of the epidemic and hence its economic and social impact. Constraining total case numbers can be achieved by a range of strategies, whereas strategies which additionally constrain peak demand for services require a more sophisticated intervention. If, for example, there are multiple objectives which must be achieved prior to the availability of a pandemic vaccine (i.e., a time-limited intervention), our analysis shows that interventions should be implemented several weeks into the epidemic, not at the very start. This observation is shown to be robust across a range of constraints and for uncertainty in estimates of both R(0) and the timing of vaccine availability. These analyses highlight the need for more precise statements of policy objectives and their assumed consequences when planning and implementing strategies to mitigate the impact of an influenza pandemic.     

A One Health Framework for the Evaluation of Rabies Control Programmes: A Case Study from Colombo City,Sri Lanka

Background

One Health addresses complex challenges to promote the health of all species and the environment by integrating relevant sciences at systems level. Its application to zoonotic diseases is recommended, but few coherent frameworks exist that combine approaches from multiple disciplines. Rabies requires an interdisciplinary approach for effective and efficient management.

Methodology/Principal Findings

A framework is proposed to assess the value of rabies interventions holistically. The economic assessment compares additional monetary and non-monetary costs and benefits of an intervention taking into account epidemiological, animal welfare, societal impact and cost data. It is complemented by an ethical assessment. The framework is applied to Colombo City, Sri Lanka, where modified dog rabies intervention measures were implemented in 2007. The two options included for analysis were the control measures in place until 2006 (“baseline scenario”) and the new comprehensive intervention measures (“intervention”) for a four-year duration. Differences in control cost; monetary human health costs after exposure; Disability-Adjusted Life Years (DALYs) lost due to human rabies deaths and the psychological burden following a bite; negative impact on animal welfare; epidemiological indicators; social acceptance of dogs; and ethical considerations were estimated using a mixed method approach including primary and secondary data. Over the four years analysed, the intervention cost US $1.03 million more than the baseline scenario in 2011 prices (adjusted for inflation) and caused a reduction in dog rabies cases; 738 DALYs averted; an increase in acceptability among non-dog owners; a perception of positive changes in society including a decrease in the number of roaming dogs; and a net reduction in the impact on animal welfare from intermediate-high to low-intermediate.

Conclusions

The findings illustrate the multiple outcomes relevant to stakeholders and allow greater understanding of the value of the implemented rabies control measures, thereby providing a solid foundation for informed decision-making and sustainable control.     

Investing in early human development: Timing and economic efficiency

Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the “antenatal investment hypothesis”. We conclude by discussing a suite of new European interventions that will inform this optimal timing debate.     

Optimal Allocation of Resources in Female Sex Worker Targeted HIV Prevention Interventions: Model Insights from Avahan in South India

Background

The Avahan programme has provided HIV prevention activities, including condom promotion, to female sex workers (FSWs) in southern India since 2004. Evidence suggests Avahan averted 202,000 HIV infections over 4 years. For replicating this intervention elsewhere, it is essential to understand how the intervention’s impact could have been optimised for different budget levels.

Methods

Behavioural data were used to determine how condom use varied for FSWs with different levels of intervention intensity. Cost data from 64 Avahan districts quantified how district-level costs related to intervention scale and intensity. A deterministic model for HIV transmission amongst FSWs and clients projected the impact and cost of intervention strategies for different scale and intensity, and identified the optimal strategies that maximise impact for different budget levels.

Results

As budget levels increase, the optimal intervention strategy is to first increase intervention intensity which achieves little impact, then scale-up coverage to high levels for large increases in impact, and lastly increase intensity further for small additional gains. The cost-effectiveness of these optimal strategies generally improves with increasing resources, while straying from these strategies can triple costs for the same impact. Projections suggest Avahan was close to being optimal, and moderate budget reductions (≥20%) would have reduced impact considerably (>40%).

Discussion

Our analysis suggests that tailoring the design of HIV prevention programmes for FSWs can improve impact, and that a certain level of resources are required to achieve demonstrable impact. These insights are critical for optimising the use of limited resources for preventing HIV.     

Decay of Impact after Self-Management Education for People with Chronic Illnesses: Changes in Anxiety and Depression over One Year

Background

In people with chronic illnesses, self-management education can reduce anxiety and depression. Those benefits, however, decay over time. Efforts have been made to prevent or minimize that “decay of impact”, but they have not been based on information about the decay’s characteristics, and they have failed. Here we show how the decay’s basic characteristics (prevalence, timing, and magnitude) can be quantified. Regarding anxiety and depression, we also report the prevalence, timing, and magnitude of the decay.

Methods

Adults with various chronic conditions participated in a self-management educational program (n = 369). Data were collected with the Hospital Anxiety and Depression Scale four times over one year. Using within-person effect sizes, we defined decay of impact as a decline of ≥0.5 standard deviations after improvement by at least the same amount. We also interpret the results using previously-set criteria for non-cases, possible cases, and probable cases.

Results

Prevalence: On anxiety, decay occurred in 19% of the participants (70/369), and on depression it occurred in 24% (90/369). Timing: In about one third of those with decay, it began 3 months after the baseline measurement (6 weeks after the educational program ended). Magnitude: The median magnitudes of decay on anxiety and on depression were both 4 points, which was about 1 standard deviation. Early in the follow-up year, many participants with decay moved into less severe clinical categories (e.g., becoming non-cases). Later, many of them moved into more severe categories (e.g., becoming probable cases).

Conclusions

Decay of impact can be identified and quantified from within-person effect sizes. This decay occurs in about one fifth or more of this program’s participants. It can start soon after the program ends, and it is large enough to be clinically important. These findings can be used to plan interventions aimed at preventing or minimizing the decay of impact.     

Dynamics of COVID-19 under social distancing measures are driven by transmission network structure

In the absence of pharmaceutical interventions, social distancing is being used worldwide to curb the spread of COVID-19. The impact of these measures has been inconsistent, with some regions rapidly nearing disease elimination and others seeing delayed peaks or nearly flat epidemic curves. Here we build a stochastic epidemic model to examine the effects of COVID-19 clinical progression and transmission network structure on the outcomes of social distancing interventions. Our simulations show that long delays between the adoption of control measures and observed declines in cases, hospitalizations, and deaths occur in many scenarios. We find that the strength of within-household transmission is a critical determinant of success, governing the timing and size of the epidemic peak, the rate of decline, individual risks of infection, and the success of partial relaxation measures. The structure of residual external connections, driven by workforce participation and essential businesses, interacts to determine outcomes. We suggest limited conditions under which the formation of household “bubbles” can be safe. These findings can improve future predictions of the timescale and efficacy of interventions needed to control second waves of COVID-19 as well as other similar outbreaks, and highlight the need for better quantification and control of household transmission.     

Achieving a “Grand Convergence” in Global Health: Modeling the Technical Inputs,Costs, and Impacts from 2016 to 2030

Background

The Commission on Investing in Health published its report, GlobalHealth2035, in 2013, estimating an investment case for a grand convergence in health outcomes globally. In support of the drafting of the Sustainable Development Goals (SDGs), we estimate what the grand convergence investment case might achieve—and what investment would be required—by 2030.

Methods and Findings

Our projection focuses on a sub-set of low-income (LIC) or lower-middle-income countries (LMIC). We start with a country-based (bottom-up) analysis of the costs and impact of scaling up reproductive, maternal, and child health tools, and select HIV and malaria interventions. We then incorporate global (top-down) analyses of the costs and impacts of scaling up existing tools for tuberculosis, additional HIV interventions, the costs to strengthen health systems, and the costs and benefits from scaling up new health interventions over the time horizon of this forecast. These data are then allocated to individual countries to provide an aggregate projection of potential cost and impact at the country level. Finally, incremental costs of R&D for low-income economies and the costs of addressing NTDs are added to provide a global total cost estimate of the investment scenario.

Results

Compared with a constant coverage scenario, there would be more than 60 million deaths averted in LIC and 70 million deaths averted in LMIC between 2016 and 2030. For the years 2015, 2020, 2025, and 2030, the incremental costs of convergence in LIC would be (US billion) $24.3, $21.8, $24.7, and $27, respectively; in LMIC, the incremental costs would be (US billion) $34.75, $38.9, $48.7, and $56.3, respectively.

Conclusion

Key health outcomes in low- and low-middle income countries can significantly converge with those of wealthier countries by 2030, and the notion of a “grand convergence” may serve as a unifying theme for health indicators in the SDGs.     

An Economic Analysis of Strategies to Control Clostridium Difficile Transmission and Infection Using an Agent-Based Simulation Model

Background

A number of strategies exist to reduce Clostridium difficile (C. difficile) transmission. We conducted an economic evaluation of “bundling” these strategies together.

Methods

We constructed an agent-based computer simulation of nosocomial C. difficile transmission and infection in a hospital setting. This model included the following components: interactions between patients and health care workers; room contamination via C. difficile shedding; C. difficile hand carriage and removal via hand hygiene; patient acquisition of C. difficile via contact with contaminated rooms or health care workers; and patient antimicrobial use. Six interventions were introduced alone and "bundled" together: (a) aggressive C. difficile testing; (b) empiric isolation and treatment of symptomatic patients; (c) improved adherence to hand hygiene and (d) contact precautions; (e) improved use of soap and water for hand hygiene; and (f) improved environmental cleaning. Our analysis compared these interventions using values representing 3 different scenarios: (1) base-case (BASE) values that reflect typical hospital practice, (2) intervention (INT) values that represent implementation of hospital-wide efforts to reduce C. diff transmission, and (3) optimal (OPT) values representing the highest expected results from strong adherence to the interventions. Cost parameters for each intervention were obtained from published literature. We performed our analyses assuming low, normal, and high C. difficile importation prevalence and transmissibility of C. difficile.

Results

INT levels of the “bundled” intervention were cost-effective at a willingness-to-pay threshold of $100,000/quality-adjusted life-year in all importation prevalence and transmissibility scenarios. OPT levels of intervention were cost-effective for normal and high importation prevalence and transmissibility scenarios. When analyzed separately, hand hygiene compliance, environmental decontamination, and empiric isolation and treatment were the interventions that had the greatest impact on both cost and effectiveness.

Conclusions

A combination of available interventions to prevent CDI is likely to be cost-effective but the cost-effectiveness varies for different levels of intensity of the interventions depending on epidemiological conditions such as C. difficile importation prevalence and transmissibility.     

Cost-Effectiveness of Preventing Loss to Follow-up in HIV Treatment Programs: A C?te d'Ivoire Appraisal

Background

Data from HIV treatment programs in resource-limited settings show extensive rates of loss to follow-up (LTFU) ranging from 5% to 40% within 6 mo of antiretroviral therapy (ART) initiation. Our objective was to project the clinical impact and cost-effectiveness of interventions to prevent LTFU from HIV care in West Africa.

Methods and Findings

We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) International model to project the clinical benefits and cost-effectiveness of LTFU-prevention programs from a payer perspective. These programs include components such as eliminating ART co-payments, eliminating charges to patients for opportunistic infection-related drugs, improving personnel training, and providing meals and reimbursing for transportation for participants. The efficacies and costs of these interventions were extensively varied in sensitivity analyses. We used World Health Organization criteria of <3× gross domestic product per capita (3× GDP per capita = US$2,823 for Côte d''Ivoire) as a plausible threshold for “cost-effectiveness.” The main results are based on a reported 18% 1-y LTFU rate. With full retention in care, projected per-person discounted life expectancy starting from age 37 y was 144.7 mo (12.1 y). Survival losses from LTFU within 1 y of ART initiation ranged from 73.9 to 80.7 mo. The intervention costing US$22/person/year (e.g., eliminating ART co-payment) would be cost-effective with an efficacy of at least 12%. An intervention costing US$77/person/year (inclusive of all the components described above) would be cost-effective with an efficacy of at least 41%.

Conclusions

Interventions that prevent LTFU in resource-limited settings would substantially improve survival and would be cost-effective by international criteria with efficacy of at least 12%–41%, depending on the cost of intervention, based on a reported 18% cumulative incidence of LTFU at 1 y after ART initiation. The commitment to start ART and treat HIV in these settings should include interventions to prevent LTFU. Please see later in the article for the Editors'' Summary     

Searching PubMed during a Pandemic

Background

The 2009 influenza A(H1N1) pandemic has generated thousands of articles and news items. However, finding relevant scientific articles in such rapidly developing health crises is a major challenge which, in turn, can affect decision-makers'' ability to utilise up-to-date findings and ultimately shape public health interventions. This study set out to show the impact that the inconsistent naming of the pandemic can have on retrieving relevant scientific articles in PubMed/MEDLINE.

Methodology

We first formulated a PubMed search algorithm covering different names of the influenza pandemic and simulated the results that it would have retrieved from weekly searches for relevant new records during the first 10 weeks of the pandemic. To assess the impact of failing to include every term in this search, we then conducted the same searches but omitted in turn “h1n1,” “swine,” “influenza” and “flu” from the search string, and compared the results to those for the full string.

Principal Findings

On average, our core search string identified 44.3 potentially relevant new records at the end of each week. Of these, we determined that an average of 27.8 records were relevant. When we excluded one term from the string, the percentage of records missed out of the total number of relevant records averaged 18.7% for omitting “h1n1,” 13.6% for “swine,” 17.5% for “influenza,” and 20.6% for “flu.”

Conclusions

Due to inconsistent naming, while searching for scientific material about rapidly evolving situations such as the influenza A(H1N1) pandemic, there is a risk that one will miss relevant articles. To address this problem, the international scientific community should agree on nomenclature and the specific name to be used earlier, and the National Library of Medicine in the US could index potentially relevant materials faster and allow publishers to add alert tags to such materials.     

Prevention of violence against women and girls: A cost-effectiveness study across 6 low- and middle-income countries

BackgroundViolence against women and girls (VAWG) is a human rights violation with social, economic, and health consequences for survivors, perpetrators, and society. Robust evidence on economic, social, and health impact, plus the cost of delivery of VAWG prevention, is critical to making the case for investment, particularly in low- and middle-income countries (LMICs) where health sector resources are highly constrained. We report on the costs and health impact of VAWG prevention in 6 countries.Methods and findingsWe conducted a trial-based cost-effectiveness analysis of VAWG prevention interventions using primary data from 5 randomised controlled trials (RCTs) in sub-Saharan Africa and 1 in South Asia. We evaluated 2 school-based interventions aimed at adolescents (11 to 14 years old) and 2 workshop-based (small group or one to one) interventions, 1 community-based intervention, and 1 combined small group and community-based programme all aimed at adult men and women (18+ years old). All interventions were delivered between 2015 and 2018 and were compared to a do-nothing scenario, except for one of the school-based interventions (government-mandated programme) and for the combined intervention (access to financial services in small groups). We computed the health burden from VAWG with disability-adjusted life year (DALY). We estimated per capita DALYs averted using statistical models that reflect each trial’s design and any baseline imbalances. We report cost-effectiveness as cost per DALY averted and characterise uncertainty in the estimates with probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEACs), which show the probability of cost-effectiveness at different thresholds. We report a subgroup analysis of the small group component of the combined intervention and no other subgroup analysis. We also report an impact inventory to illustrate interventions’ socioeconomic impact beyond health. We use a 3% discount rate for investment costs and a 1-year time horizon, assuming no effects post the intervention period. From a health sector perspective, the cost per DALY averted varies between US$222 (2018), for an established gender attitudes and harmful social norms change community-based intervention in Ghana, to US$17,548 (2018) for a livelihoods intervention in South Africa. Taking a societal perspective and including wider economic impact improves the cost-effectiveness of some interventions but reduces others. For example, interventions with positive economic impacts, often those with explicit economic goals, offset implementation costs and achieve more favourable cost-effectiveness ratios. Results are robust to sensitivity analyses. Our DALYs include a subset of the health consequences of VAWG exposure; we assume no mortality impact from any of the health consequences included in the DALYs calculations. In both cases, we may be underestimating overall health impact. We also do not report on participants’ health costs.ConclusionsWe demonstrate that investment in established community-based VAWG prevention interventions can improve population health in LMICs, even within highly constrained health budgets. However, several VAWG prevention interventions require further modification to achieve affordability and cost-effectiveness at scale. Broadening the range of social, health, and economic outcomes captured in future cost-effectiveness assessments remains critical to justifying the investment urgently required to prevent VAWG globally.

In a cost-effectiveness study, Dr. Giulia Ferrari and colleagues examine the costs and health impact of prevention of violence against women and girls in six low- and middle-income countries.     

Effectiveness of cash-plus programmes on early childhood outcomes compared to cash transfers alone: A systematic review and meta-analysis in low- and middle-income countries

BackgroundTo strengthen the impact of cash transfers, these interventions have begun to be packaged as cash-plus programmes, combining cash with additional transfers, interventions, or services. The intervention’s complementary (“plus”) components aim to improve cash transfer effectiveness by targeting mediating outcomes or the availability of supplies or services. This study examined whether cash-plus interventions for infants and children <5 are more effective than cash alone in improving health and well-being.Methods and findingsForty-two databases, donor agencies, grey literature sources, and trial registries were systematically searched, yielding 5,097 unique articles (as of 06 April 2021). Randomised and quasi-experimental studies were eligible for inclusion if the intervention package aimed to improve outcomes for children <5 in low- and middle-income countries (LMICs) and combined a cash transfer with an intervention targeted to Sustainable Development Goal (SDG) 2 (No Hunger), SDG3 (Good Health and Well-being), SDG4 (Education), or SDG16 (Violence Prevention), had at least one group receiving cash-only, examined outcomes related to child-focused SDGs, and was published in English. Risk of bias was appraised using Cochrane Risk of Bias and ROBINS-I Tools. Random effects meta-analyses were conducted for a cash-plus intervention category when there were at least 3 trials with the same outcome. The review was preregistered with PROSPERO (CRD42018108017). Seventeen studies were included in the review and 11 meta-analysed. Most interventions operated during the first 1,000 days of the child’s life and were conducted in communities facing high rates of poverty and often, food insecurity. Evidence was found for 10 LMICs, where most researchers used randomised, longitudinal study designs (n = 14). Five intervention categories were identified, combining cash with nutrition behaviour change communication (BCC, n = 7), food transfers (n = 3), primary healthcare (n = 2), psychosocial stimulation (n = 7), and child protection (n = 4) interventions. Comparing cash-plus to cash alone, meta-analysis results suggest Cash + Food Transfers are more effective in improving height-for-age (d = 0.08 SD (0.03, 0.14), p = 0.02) with significantly reduced odds of stunting (OR = 0.82 (0.74, 0.92), p = 0.01), but had no added impact in improving weight-for-height (d = −0.13 (−0.42, 0.16), p = 0.24) or weight-for-age z-scores (d = −0.06 (−0.28, 0.15), p = 0.43). There was no added impact above cash alone from Cash + Nutrition BCC on anthropometrics; Cash + Psychosocial Stimulation on cognitive development; or Cash + Child Protection on parental use of violent discipline or exclusive positive parenting. Narrative synthesis evidence suggests that compared to cash alone, Cash + Primary Healthcare may have greater impacts in reducing mortality and Cash + Food Transfers in preventing acute malnutrition in crisis contexts. The main limitations of this review are the few numbers of studies that compared cash-plus interventions against cash alone and the potentially high heterogeneity between study findings.ConclusionsIn this study, we observed that few cash-plus combinations were more effective than cash transfers alone. Cash combined with food transfers and primary healthcare show the greatest signs of added effectiveness. More research is needed on when and how cash-plus combinations are more effective than cash alone, and work in this field must ensure that these interventions improve outcomes among the most vulnerable children.

In a systematic review and meta analysis, Madison Little and colleagues examine whether cash-plus programmes combined with additional interventions are more effective than cash transfers alone in improving health and wellbeing outcomes for children under 5 in low and middle income countries.     

Ungulate Reproductive Parameters Track Satellite Observations of Plant Phenology across Latitude and Climatological Regimes

The effect of climatically-driven plant phenology on mammalian reproduction is one key to predicting species-specific demographic responses to climate change. Large ungulates face their greatest energetic demands from the later stages of pregnancy through weaning, and so in seasonal environments parturition dates should match periods of high primary productivity. Interannual variation in weather influences the quality and timing of forage availability, which can influence neonatal survival. Here, we evaluated macro-scale patterns in reproductive performance of a widely distributed ungulate (mule deer, Odocoileus hemionus) across contrasting climatological regimes using satellite-derived indices of primary productivity and plant phenology over eight degrees of latitude (890 km) in the American Southwest. The dataset comprised > 180,000 animal observations taken from 54 populations over eight years (2004–2011). Regionally, both the start and peak of growing season (“Start” and “Peak”, respectively) are negatively and significantly correlated with latitude, an unusual pattern stemming from a change in the dominance of spring snowmelt in the north to the influence of the North American Monsoon in the south. Corresponding to the timing and variation in both the Start and Peak, mule deer reproduction was latest, lowest, and most variable at lower latitudes where plant phenology is timed to the onset of monsoonal moisture. Parturition dates closely tracked the growing season across space, lagging behind the Start and preceding the Peak by 27 and 23 days, respectively. Mean juvenile production increased, and variation decreased, with increasing latitude. Temporally, juvenile production was best predicted by primary productivity during summer, which encompassed late pregnancy, parturition, and early lactation. Our findings offer a parsimonious explanation of two key reproductive parameters in ungulate demography, timing of parturition and mean annual production, across latitude and changing climatological regimes. Practically, this demonstrates the potential for broad-scale modeling of couplings between climate, plant phenology, and animal populations using space-borne observations.     

Tuberculosis Prevention in South Africa

Background

South Africa has one of the highest per capita rates of tuberculosis (TB) incidence in the world. In 2012, the South African government produced a National Strategic Plan (NSP) to control the spread of TB with the ambitious aim of zero new TB infections and deaths by 2032, and a halving of the 2012 rates by 2016.

Methods

We used a transmission model to investigate whether the NSP targets could be reached if immediate scale up of control methods had happened in 2014. We explored the potential impact of four intervention portfolios; 1) “NSP” represents the NSP strategy, 2) “WHO” investigates increasing antiretroviral therapy eligibility, 3) “Novel Strategies” considers new isoniazid preventive therapy strategies and HIV “Universal Test and Treat” and 4) “Optimised” contains the most effective interventions.

Findings

We find that even with this scale-up, the NSP targets are unlikely to be achieved. The portfolio that achieved the greatest impact was “Optimised”, followed closely by “NSP”. The “WHO” and “Novel Strategies” had little impact on TB incidence by 2050. Of the individual interventions explored, the most effective were active case finding and reductions in pre-treatment loss to follow up which would have a large impact on TB burden.

Conclusion

Use of existing control strategies has the potential to have a large impact on TB disease burden in South Africa. However, our results suggest that the South African TB targets are unlikely to be reached without new technologies. Despite this, TB incidence could be dramatically reduced by finding and starting more TB cases on treatment.     

Building and experimenting with an agent-based model to study the population-level impact of CommunityRx,a clinic-based community resource referral intervention

CommunityRx (CRx), an information technology intervention, provides patients with a personalized list of healthful community resources (HealtheRx). In repeated clinical studies, nearly half of those who received clinical “doses” of the HealtheRx shared their information with others (“social doses”). Clinical trial design cannot fully capture the impact of information diffusion, which can act as a force multiplier for the intervention. Furthermore, experimentation is needed to understand how intervention delivery can optimize social spread under varying circumstances. To study information diffusion from CRx under varying conditions, we built an agent-based model (ABM). This study describes the model building process and illustrates how an ABM provides insight about information diffusion through in silico experimentation. To build the ABM, we constructed a synthetic population (“agents”) using publicly-available data sources. Using clinical trial data, we developed empirically-informed processes simulating agent activities, resource knowledge evolution and information sharing. Using RepastHPC and chiSIM software, we replicated the intervention in silico, simulated information diffusion processes, and generated emergent information diffusion networks. The CRx ABM was calibrated using empirical data to replicate the CRx intervention in silico. We used the ABM to quantify information spread via social versus clinical dosing then conducted information diffusion experiments, comparing the social dosing effect of the intervention when delivered by physicians, nurses or clinical clerks. The synthetic population (N = 802,191) exhibited diverse behavioral characteristics, including activity and knowledge evolution patterns. In silico delivery of the intervention was replicated with high fidelity. Large-scale information diffusion networks emerged among agents exchanging resource information. Varying the propensity for information exchange resulted in networks with different topological characteristics. Community resource information spread via social dosing was nearly 4 fold that from clinical dosing alone and did not vary by delivery mode. This study, using CRx as an example, demonstrates the process of building and experimenting with an ABM to study information diffusion from, and the population-level impact of, a clinical information-based intervention. While the focus of the CRx ABM is to recreate the CRx intervention in silico, the general process of model building, and computational experimentation presented is generalizable to other large-scale ABMs of information diffusion.     

Effect of a musical intervention on tolerance and efficacy of non-invasive ventilation in the ICU: study protocol for a randomized controlled trial (MUSique pour l’Insuffisance Respiratoire Aigue - Mus-IRA)

BackgroundNon-invasive ventilation (NIV) tolerance is a key factor of NIV success. Hence, numerous sedative pharmacological or non-pharmacological strategies have been assessed to improve NIV tolerance. Music therapy in various health care settings has shown beneficial effects. In invasively ventilated critical care patients, encouraging results of music therapy on physiological parameters, anxiety, and agitation have been reported. We hypothesize that a musical intervention improves NIV tolerance in comparison to conventional care. We therefore question the potential benefit of a receptive music session administered to patients by trained caregivers (“musical intervention”) to enhance acceptance and tolerance of NIV.Methods/designWe conduct a prospective, three-center, open-label, three-arm randomized trial involving patients in the intensive care unit (ICU) who require NIV, as assessed by the treating physician. Participants are allocated to a “musical intervention” arm (“musical intervention” applied during all NIV sessions), to a “sensory deprivation” arm (sight and hearing isolation during all NIV sessions), or to the control group. The primary endpoint is the change in respiratory comfort (measured with a digital visual scale) before the initiation and after 30 minutes of the first NIV session. The evaluation of the primary endpoint is performed blindly from the treatment group. Secondary endpoints include changes in respiratory and cardiovascular parameters during NIV sessions, the percentage of patients requiring endotracheal intubation, day-90 anxiety/depression and health-related quality of life, post-trauma stress induced by NIV, and the overall assessment of NIV.The follow-up for each participant is 90 days. We expect to randomize a total of 99 participants.DiscussionAs music intervention is a simple and easy-to-implement non-pharmacological technique, efficacious in reducing anxiety in critically ill patients, it appeared logical to assess its efficacy in NIV, one of the most stressful techniques used in the ICU. Patient centeredness was crucial in choosing the outcomes assessed.

Trial registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT02265458","term_id":"NCT02265458"}}NCT02265458. Registered on 25 August 2014.

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1574-z) contains supplementary material, which is available to authorized users.     

The Effectiveness of Different Interventions to Promote Poison Prevention Behaviours in Households with Children: A Network Meta-Analysis

Background

There is evidence from 2 previous meta-analyses that interventions to promote poison prevention behaviours are effective in increasing a range of poison prevention practices in households with children. The published meta-analyses compared any intervention against a “usual care or no intervention” which potentially limits the usefulness of the analysis to decision makers. We aim to use network meta-analysis to simultaneously evaluate the effectiveness of different interventions to increase prevalence of safe storage of i) Medicines only, ii) Other household products only, iii) Poisons (both medicines and non-medicines), iv) Poisonous plants; and v) Possession of poison control centre (PCC) telephone number in households with children.

Methods

Data on the effectiveness of poison prevention interventions was extracted from primary studies identified in 2 newly-undertaken systematic reviews. Effect estimates were pooled across studies using a random effects network meta-analysis model.

Results

28 of the 47 primary studies identified were included in the analysis. Compared to usual care intervention, the intervention with education and low cost/free equipment elements was most effective in promoting safe storage of medicines (odds ratio 2.51, 95% credible interval 1.01 to 6.00) while interventions with education, low cost/free equipment, home safety inspection and fitting components were most effective in promoting safe storage of other household products (2.52, 1.12 to 7.13), safe storage of poisons (11.10, 1.60 to 141.50) and possession of PCC number (38.82, 2.19 to 687.10). No one intervention package was more effective than the others in promoting safe storage of poisonous plants.

Conclusion

The most effective interventions varied by poison prevention practice, but education alone was not the most effective intervention for any poison prevention practice. Commissioners and providers of poison prevention interventions should tailor the interventions they commission or provide to the poison prevention practices they wish to promote.

Highlights

• Network meta-analysis is useful for comparing multiple injury-prevention interventions.
• More intensive poison prevention interventions were more effective than education alone.
• Education and low cost/free equipment was most effective in promoting safe storage of medicines.
• Education, low cost/free equipment, home safety inspection and fitting was most effective in promoting safe storage of household products and poisons.
• Education, low cost/free equipment and home inspection were most effective in promoting possession of a poison control centre number.
• None of the intervention packages was more effective than the others in promoting safe storage of poisonous plants.

     

Multimorbidity combinations,costs of hospital care and potentially preventable emergency admissions in England: A cohort study

BackgroundPatients with multimorbidities have the greatest healthcare needs and generate the highest expenditure in the health system. There is an increasing focus on identifying specific disease combinations for addressing poor outcomes. Existing research has identified a small number of prevalent “clusters” in the general population, but the limited number examined might oversimplify the problem and these may not be the ones associated with important outcomes. Combinations with the highest (potentially preventable) secondary care costs may reveal priority targets for intervention or prevention. We aimed to examine the potential of defining multimorbidity clusters for impacting secondary care costs.Methods and findingsWe used national, Hospital Episode Statistics, data from all hospital admissions in England from 2017/2018 (cohort of over 8 million patients) and defined multimorbidity based on ICD-10 codes for 28 chronic conditions (we backfilled conditions from 2009/2010 to address potential undercoding). We identified the combinations of multimorbidity which contributed to the highest total current and previous 5-year costs of secondary care and costs of potentially preventable emergency hospital admissions in aggregate and per patient. We examined the distribution of costs across unique disease combinations to test the potential of the cluster approach for targeting interventions at high costs. We then estimated the overlap between the unique combinations to test potential of the cluster approach for targeting prevention of accumulated disease. We examined variability in the ranks and distributions across age (over/under 65) and deprivation (area level, deciles) subgroups and sensitivity to considering a smaller number of diseases.There were 8,440,133 unique patients in our sample, over 4 million (53.1%) were female, and over 3 million (37.7%) were aged over 65 years. No clear “high cost” combinations of multimorbidity emerged as possible targets for intervention. Over 2 million (31.6%) patients had 63,124 unique combinations of multimorbidity, each contributing a small fraction (maximum 3.2%) to current-year or 5-year secondary care costs. Highest total cost combinations tended to have fewer conditions (dyads/triads, most including hypertension) affecting a relatively large population. This contrasted with the combinations that generated the highest cost for individual patients, which were complex sets of many (6+) conditions affecting fewer persons. However, all combinations containing chronic kidney disease and hypertension, or diabetes and hypertension, made up a significant proportion of total secondary care costs, and all combinations containing chronic heart failure, chronic kidney disease, and hypertension had the highest proportion of preventable emergency admission costs, which might offer priority targets for prevention of disease accumulation. The results varied little between age and deprivation subgroups and sensitivity analyses.Key limitations include availability of data only from hospitals and reliance on hospital coding of health conditions.ConclusionsOur findings indicate that there are no clear multimorbidity combinations for a cluster-targeted intervention approach to reduce secondary care costs. The role of risk-stratification and focus on individual high-cost patients with interventions is particularly questionable for this aim. However, if aetiology is favourable for preventing further disease, the cluster approach might be useful for targeting disease prevention efforts with potential for cost-savings in secondary care.

Jonathan Stokes and co-workers explore patterns of multimorbidity and implications for the organization and costs of care.     

Modeling Social Transmission Dynamics of Unhealthy Behaviors for Evaluating Prevention and Treatment Interventions on Childhood Obesity

Research evidence indicates that obesity has spread through social networks, but lever points for interventions based on overlapping networks are not well studied. The objective of our research was to construct and parameterize a system dynamics model of the social transmission of behaviors through adult and youth influence in order to explore hypotheses and identify plausible lever points for future childhood obesity intervention research. Our objectives were: (1) to assess the sensitivity of childhood overweight and obesity prevalence to peer and adult social transmission rates, and (2) to test the effect of combinations of prevention and treatment interventions on the prevalence of childhood overweight and obesity. To address the first objective, we conducted two-way sensitivity analyses of adult-to-child and child-to-child social transmission in relation to childhood overweight and obesity prevalence. For the second objective, alternative combinations of prevention and treatment interventions were tested by varying model parameters of social transmission and weight loss behavior rates. Our results indicated child overweight and obesity prevalence might be slightly more sensitive to the same relative change in the adult-to-child compared to the child-to-child social transmission rate. In our simulations, alternatives with treatment alone, compared to prevention alone, reduced the prevalence of childhood overweight and obesity more after 10 years (1.2–1.8% and 0.2–1.0% greater reduction when targeted at children and adults respectively). Also, as the impact of adult interventions on children was increased, the rank of six alternatives that included adults became better (i.e., resulting in lower 10 year childhood overweight and obesity prevalence) than alternatives that only involved children. The findings imply that social transmission dynamics should be considered when designing both prevention and treatment intervention approaches. Finally, targeting adults may be more efficient, and research should strengthen and expand adult-focused interventions that have a high residual impact on children.