Saltelli Global Sensitivity Analysis and Simulation Modelling to Identify Intervention Strategies to Reduce the Prevalence of Escherichia coli O157 Contaminated Beef Carcasses

Introduction

Strains of Shiga-toxin producing Escherichia coli O157 (STEC O157) are important foodborne pathogens in humans, and outbreaks of illness have been associated with consumption of undercooked beef. Here, we determine the most effective intervention strategies to reduce the prevalence of STEC O157 contaminated beef carcasses using a modelling approach.

Method

A computational model simulated events and processes in the beef harvest chain. Information from empirical studies was used to parameterise the model. Variance-based global sensitivity analysis (GSA) using the Saltelli method identified variables with the greatest influence on the prevalence of STEC O157 contaminated carcasses. Following a baseline scenario (no interventions), a series of simulations systematically introduced and tested interventions based on influential variables identified by repeated Saltelli GSA, to determine the most effective intervention strategy.

Results

Transfer of STEC O157 from hide or gastro-intestinal tract to carcass (improved abattoir hygiene) had the greatest influence on the prevalence of contaminated carcases. Due to interactions between inputs (identified by Saltelli GSA), combinations of interventions based on improved abattoir hygiene achieved a greater reduction in maximum prevalence than would be expected from an additive effect of single interventions. The most effective combination was improved abattoir hygiene with vaccination, which achieved a greater than ten-fold decrease in maximum prevalence compared to the baseline scenario.

Conclusion

Study results suggest that effective interventions to reduce the prevalence of STEC O157 contaminated carcasses should initially be based on improved abattoir hygiene. However, the effect of improved abattoir hygiene on the distribution of STEC O157 concentration on carcasses is an important information gap—further empirical research is required to determine whether reduced prevalence of contaminated carcasses is likely to result in reduced incidence of STEC O157 associated illness in humans. This is the first use of variance-based GSA to assess the drivers of STEC O157 contamination of beef carcasses.     

Road Traffic Injury Prevention Initiatives: A Systematic Review and Metasummary of Effectiveness in Low and Middle Income Countries

Background

Road traffic injuries (RTIs) are a growing but neglected global health crisis, requiring effective prevention to promote sustainable safety. Low- and middle-income countries (LMICs) share a disproportionately high burden with 90% of the world’s road traffic deaths, and where RTIs are escalating due to rapid urbanization and motorization. Although several studies have assessed the effectiveness of a specific intervention, no systematic reviews have been conducted summarizing the effectiveness of RTI prevention initiatives specifically performed in LMIC settings; this study will help fill this gap.

Methods

In accordance with PRISMA guidelines we searched the electronic databases MEDLINE, EMBASE, Scopus, Web of Science, TRID, Lilacs, Scielo and Global Health. Articles were eligible if they considered RTI prevention in LMICs by evaluating a prevention-related intervention with outcome measures of crash, RTI, or death. In addition, a reference and citation analysis was conducted as well as a data quality assessment. A qualitative metasummary approach was used for data analysis and effect sizes were calculated to quantify the magnitude of emerging themes.

Results

Of the 8560 articles from the literature search, 18 articles from 11 LMICs fit the eligibility and inclusion criteria. Of these studies, four were from Sub-Saharan Africa, ten from Latin America and the Caribbean, one from the Middle East, and three from Asia. Half of the studies focused specifically on legislation, while the others focused on speed control measures, educational interventions, enforcement, road improvement, community programs, or a multifaceted intervention.

Conclusion

Legislation was the most common intervention evaluated with the best outcomes when combined with strong enforcement initiatives or as part of a multifaceted approach. Because speed control is crucial to crash and injury prevention, road improvement interventions in LMIC settings should carefully consider how the impact of improvements will affect speed and traffic flow. Further road traffic injury prevention interventions should be performed in LMICs with patient-centered outcomes in order to guide injury prevention in these complex settings.     

Interventions to Improve Adherence in Patients with Immune-Mediated Inflammatory Disorders: A Systematic Review

Background

In patients with immune-mediated inflammatory disorders, poor adherence to medication is associated with increased healthcare costs, decreased patient satisfaction, reduced quality of life and unfavorable treatment outcomes.

Objective

To determine the impact of different interventions on medication adherence in patients with immune-mediated inflammatory disorders.

Design

Systematic review.

Data sources

MEDLINE, EMBASE and Cochrane Library.

Study eligibility criteria for selecting studies

Included studies were clinical trials and observational studies in adult outpatients treated for psoriasis, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, spondyloarthritis, psoriatic arthritis or multiple sclerosis.

Study appraisal and synthesis methods

Intervention approaches were classified into four categories: educational, behavioral, cognitive behavioral, and multicomponent interventions. The risk of bias/study limitations of each study was assessed using the GRADE system.

Results

Fifteen studies (14 clinical trials and one observational study) met eligibility criteria and enrolled a total of 1958 patients. Forty percent of the studies (6/15) was conducted in patients with inflammatory bowel disease, half (7/15) in rheumatoid arthritis patients, one in psoriasis patients and one in multiple sclerosis patients. Seven out of 15 interventions were classified as multicomponent, four as educational, two as behavioral and two as cognitive behavioral. Nine studies, of which five were multicomponent interventions, had no serious limitations according to GRADE criteria. Nine out of 15 interventions showed an improvement of adherence: three multicomponent interventions in inflammatory bowel disease; one intervention of each category in rheumatoid arthritis; one multicomponent in psoriasis and one multicomponent in multiple sclerosis.

Conclusion

The assessment of interventions designed for increasing medication adherence in IMID is rare in the literature and their methodological quality may be improved in upcoming studies. Nonetheless, multicomponent interventions showed the strongest evidence for promoting adherence in patients with IMID.     

Effects of Source- versus Household Contamination of Tubewell Water on Child Diarrhea in Rural Bangladesh: A Randomized Controlled Trial

Background

Shallow tubewells are the primary drinking water source for most rural Bangladeshis. Fecal contamination has been detected in tubewells, at low concentrations at the source and at higher levels at the point of use. We conducted a randomized controlled trial to assess whether improving the microbiological quality of tubewell drinking water by household water treatment and safe storage would reduce diarrhea in children <2 years in rural Bangladesh.

Methods

We randomly assigned 1800 households with a child aged 6-18 months (index child) into one of three arms: chlorine plus safe storage, safe storage and control. We followed households with monthly visits for one year to promote the interventions, track their uptake, test participants’ source and stored water for fecal contamination, and record caregiver-reported child diarrhea prevalence (primary outcome). To assess reporting bias, we also collected data on health outcomes that are not expected to be impacted by our interventions.

Findings

Both interventions had high uptake. Safe storage, alone or combined with chlorination, reduced heavy contamination of stored water. Compared to controls, diarrhea in index children was reduced by 36% in the chlorine plus safe storage arm (prevalence ratio, PR = 0.64, 0.55-0.73) and 31% in the safe storage arm (PR = 0.69, 0.60-0.80), with no difference between the two intervention arms. One limitation of the study was the non-blinded design with self-reported outcomes. However, the prevalence of health outcomes not expected to be impacted by water interventions did not differ between study arms, suggesting minimal reporting bias.

Conclusions

Safe storage significantly improved drinking water quality at the point of use and reduced child diarrhea in rural Bangladesh. There was no added benefit from combining safe storage with chlorination. Efforts should be undertaken to implement and evaluate long-term efforts for safe water storage in Bangladesh.

Trial Registration

ClinicalTrials.gov NCT01350063     

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

Background

Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed.

Methodology/Principal Findings

Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB’s DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB.

Conclusions

Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators.     

Stand-Alone Personalized Normative Feedback for College Student Drinkers: A Meta-Analytic Review, 2004 to 2014

Background

Norms clarification has been identified as an effective component of college student drinking interventions, prompting research on norms clarification as a single-component intervention known as Personalized Normative Feedback (PNF). Previous reviews have examined PNF in combination with other components but not as a stand-alone intervention.

Objectives

To investigate the degree to which computer-delivered stand-alone personalized normative feedback interventions reduce alcohol consumption and alcohol-related harms among college students and to compare gender-neutral and gender-specific PNF.

Data Sources

Electronic databases were searched systematically through November 2014. Reference lists were reviewed manually and forward and backward searches were conducted.

Selection Criteria

Outcome studies that compared computer-delivered, stand-alone PNF intervention with an assessment only, attention-matched, or active treatment control and reported alcohol use and harms among college students.

Methods

Between-group effect sizes were calculated as the standardized mean difference in change scores between treatment and control groups divided by pooled standard deviation. Within-group effect sizes were calculated as the raw mean difference between baseline and follow-up divided by pooled within-groups standard deviation.

Results

Eight studies (13 interventions) with a total of 2,050 participants were included. Compared to control participants, students who received gender-neutral (d _between = 0.291, 95% CI [0.159, 0.423]) and gender-specific PNF (d _between = 0.284, 95% CI [0.117, 0.451]) reported greater reductions in drinking from baseline to follow-up. Students who received gender-neutral PNF reported 3.027 (95% CI [2.171, 3.882]) fewer drinks per week at first follow-up and gender-specific PNF reported 3.089 (95% CI [0.992, 5.186]) fewer drinks. Intervention effects were small for harms (d _between = 0.157, 95% CI [0.037, 0.278]).

Conclusions

Computer-delivered PNF is an effective stand-alone approach for reducing college student drinking and has a small impact on alcohol-related harms. Effects are small but clinically relevant when considered from a public health perspective. Additional research is needed to examine computer-delivered, stand-alone PNF as a population-level prevention program.     

Evaluating HIV Prevention Programs: Herpes Simplex Virus Type 2 Antibodies as Biomarker for Sexual Risk Behavior in Young Adults in Resource-Poor Countries

Background

Measuring effectiveness of HIV prevention interventions is challenged by bias when using self-reported knowledge, attitude or behavior change. HIV incidence is an objective marker to measure effectiveness of HIV prevention interventions, however, because new infection rates are relatively low, prevention studies require large sample sizes. Herpes simplex virus type 2 (HSV-2) is similarly transmitted and more prevalent and could thus serve as a proxy marker for sexual risk behavior and therefore HIV infection.

Methods

HSV-2 antibodies were assessed in a sub-study of 70,000 students participating in an education intervention in Western Province, Kenya. Feasibility of testing for HSV-2 antibodies was assessed comparing two methods using Fisher’s exact test. Three hundred and ninety four students (aged 18 to 22 years) were randomly chosen from the cohort and tested for HIV, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Out of these, 139 students were tested for HSV-2 with ELISA and surveyed for sexual risk behavior and 89 students were additionally tested for HSV-2 with a point-of-contact (POC) test.

Results

Prevalence rates were 0.5%, 1.8%, 0.3% and 2.3% for HIV, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis, respectively. Prevalence of HSV-2 antibodies was 3.4 % as measured by POC test (n=89) and 14.4 % by ELISA (n=139). Specificity of the POC test compared with ELISA was 100%, and the sensitivity only 23.1%. Associations between self-reported sexual behavior and HSV-2 serostatus could not be shown.

Conclusions

Associations between self-reported sexual risk behavior and HSV-2 serostatus could not be shown, probably due to social bias in interviews since its transmission is clearly linked. HSV-2 antibody testing is feasible in resource-poor settings and shows higher prevalence rates than other sexually transmitted diseases thus representing a potential biomarker for evaluation of HIV prevention interventions.     

Homozygosity Mapping and Targeted Sanger Sequencing Reveal Genetic Defects Underlying Inherited Retinal Disease in Families from Pakistan

Background

Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD).

Methods

We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), congenital stationary night blindness (CSNB), or cone dystrophy (CD). We employed genome-wide single nucleotide polymorphism (SNP) array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS) of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.

Results

Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.

Conclusions

Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.     

Three-Year Improvements in Weight Status and Weight-Related Behaviors in Middle School Students: The Healthy Choices Study

Introduction

Few dissemination evaluations exist to document the effectiveness of evidence-based childhood obesity interventions outside the research setting.

Objective

Evaluate Healthy Choices (HC), a multi-component obesity prevention program, by examining school-level changes in weight-related behaviors and weight status and the association of implementation components with odds of overweight/obesity.

Methods

We compared baseline and Year 3 school-level behavioral and weight status outcomes with paired t-tests adjusted for schools’ socio-demographic characteristics. We used generalized estimating equations to examine the odds of overweight/obesity associated with program components.

Setting/Participants

Consecutive sample of 45 of 51 middle schools participating in the HC program with complete baseline and follow-up survey data including a subsample of 35 schools with measured anthropomentry for 5,665 7^th grade students.

Intervention

Schools developed a multi-disciplinary team and implemented an obesity prevention curriculum, before and after school activities, environmental and policy changes and health promotions targeting a 5-2-1 theme: eat ≥ 5 servings/day of fruits and vegetables (FV), watch ≤ 2 hours of television (TV) and participate in ≥ 1 hours/day of physical activity (PA) on most days

Main Outcome Measures

1) School-level percent of students achieving targeted behaviors and percent overweight/obese; and 2) individual odds of overweight/obesity.

Results

The percent achieving behavioral goals over three years increased significantly for FV: 16.4 to 19.4 (p = 0.001), TV: 53.4 to 58.2 (p = 0.003) and PA: 37.1 to 39.9 (p = 0.02), adjusting for school size, baseline mean age and percent female, non-Hispanic White, and eligible for free and reduced price lunch. In 35 schools with anthropometry, the percent of overweight/obese 7^th grade students decreased from 42.1 to 38.4 (p = 0.016). Having a team that met the HC definition was associated with lower odds of overweight/obesity (OR = 0.83, CI: 0.71–0.98).

Conclusions and Relevance

The HC multi-component intervention demonstrated three-year improvements in weight-related behaviors and weight status across diverse middle schools. Team building appears important to the program’s effectiveness.     

Gastroenteritis Therapies in Developed Countries: Systematic Review and Meta-Analysis

Context

Gastroenteritis remains a leading cause of childhood morbidity.

Objective

Because prior reviews have focused on isolated symptoms and studies conducted in developing countries, this study focused on interventions commonly considered for use in developed countries. Intervention specific, patient-centered outcomes were selected.

Data Sources

MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, trial registries, grey literature, and scientific meetings.

Study Selection

Randomized controlled trials, conducted in developed countries, of children aged <18 years, with gastroenteritis, performed in emergency department or outpatient settings which evaluated oral rehydration therapy (ORT), antiemetics, probiotics or intravenous fluid administration rate.

Data Extraction

The study was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Data were independently extracted by multiple investigators. Analyses employed random effects models.

Results

31 trials (4,444 patients) were included. ORT: Compared with intravenous rehydration, hospitalization (RR 0.80, 95%CI 0.24, 2.71) and emergency department return visits (RR 0.86, 95%CI 0.39, 1.89) were similar. Antiemetics: Fewer children administered an antiemetic required intravenous rehydration (RR 0.40, 95%CI 0.26, 0.60) While the data could not be meta-analyzed, three studies reported that ondansetron administration does increase the frequency of diarrhea. Probiotics: No studies reported on the primary outcome, three studies evaluated hospitalization within 7 days (RR 0.87, 95%CI 0.25, 2.98). Rehydration: No difference in length of stay was identified for rapid vs. standard intravenous or nasogastric rehydration. A single study found that 5% dextrose in normal saline reduced hospitalizations compared with normal saline alone (RR 0.70, 95% CI 0.53, 0.92).

Conclusions

There is a paucity of patient-centered outcome evidence to support many interventions. Since ORT is a low-cost, non-invasive intervention, it should continue to be used. Routine probiotic use cannot be endorsed at this time in outpatient children with gastroenteritis. Despite some evidence that ondansetron administration increases diarrhea frequency, emergency department use leads to reductions in intravenous rehydration and hospitalization. No benefits were associated with ondansetron use following emergency department discharge.     

Understanding Water Storage Practices of Urban Residents of an Endemic Dengue Area in Colombia: Perceptions,Rationale and Socio-Demographic Characteristics

Introduction

The main preventive measure against dengue virus transmission is often based on actions to control Ae. Aegypti reproduction by targeting water containers of clean and stagnant water. Household water storage has received special attention in prevention strategies but the evidence about the rationale of this human practice is limited. The objective was to identify and describe water storage practices among residents of an urban area in Colombia (Girardot) and its association with reported perceptions, rationales and socio-demographic characteristics with a mixed methods approach.

Methods

Knowledge, attitudes and practices and entomological surveys from 1,721 households and 26 semi-structured interviews were conducted among residents of Girardot and technicians of the local vector borne disease program. A multivariate analysis was performed to identify associations between a water storage practice and socio-demographic characteristics, and knowledge, attitudes and practices about dengue and immature forms of the vector, which were then triangulated with qualitative information.

Results

Water storage is a cultural practice in Girardot. There are two main reasons for storage: The scarcity concern based on a long history of shortages of water in the region and the perception of high prices in water rates, contrary to what was reported by the local water company. The practice of water storage was associated with being a housewife (Inverse OR: 2.6, 95% CI 1.5 -4.3). The use of stored water depends on the type of container used, while water stored in alberca (Intra household cement basins) is mainly used for domestic cleaning chores, water in plastic containers is used for cooking.

Conclusions

It is essential to understand social practices that can increase or reduce the number of breeding sites of Ae. Aegypti. Identification of individuals who store water and the rationale of such storage allow a better understanding of the social dynamics that lead to water accumulation.     

A Meta-Analytic Review of Stand-Alone Interventions to Improve Body Image

Objective

Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image.

Methods

The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy.

Results

The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d ₊ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d ₊ = -0.37), and a large reduction in social comparison tendencies (d ₊ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated.

Conclusions

The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions.     

Meta-Analysis of a Complex Network of Non-Pharmacological Interventions: The Example of Femoral Neck Fracture

Background

Surgical interventions raise specific methodological issues in network meta-analysis (NMA). They are usually multi-component interventions resulting in complex networks of randomized controlled trials (RCTs), with multiple groups and sparse connections.

Purpose

To illustrate the applicability of the NMA in a complex network of surgical interventions and to prioritize the available interventions according to a clinically relevant outcome.

Methods

We considered RCTs of treatments for femoral neck fracture in adults. We searched CENTRAL, MEDLINE, EMBASE and ClinicalTrials.gov up to November 2015. Two reviewers independently selected trials, extracted data and used the Cochrane Collaboration’s tool for assessing the risk of bias. A group of orthopedic surgeons grouped similar but not identical interventions under the same node. We synthesized the network using a Bayesian network meta-analysis model. We derived posterior odds ratios (ORs) and 95% credible intervals (95% CrIs) for all possible pairwise comparisons. The primary outcome was all-cause revision surgery.

Results

Data from 27 trials were combined, for 4,186 participants (72% women, mean age 80 years, 95% displaced fractures). The median follow-up was 2 years. With hemiarthroplasty (HA) and total hip arthroplasty (THA) as a comparison, risk of surgical revision was significantly higher with the treatments unthreaded cervical osteosynthesis (OR 8.0 [95% CrI 3.6–15.5] and 5.9 [2.4–12.0], respectively), screw (9.4 [6.0–16.5] and 6.7 [3.9–13.6]) and plate (12.5 [5.8–23.8] and 7.8 [3.8–19.4]).

Conclusions

In older women with displaced femoral neck fractures, arthroplasty (HA and THA) is the most effective treatment in terms of risk of revision surgery.

Systematic Review Registration

PROSPERO no. CRD42013004218.

Level of Evidence

Network Meta-Analysis, Level 1.     

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.     

Improved Quantification,Propagation, Purification and Storage of the Obligate Intracellular Human Pathogen Orientia tsutsugamushi

Background

Scrub typhus is a leading cause of serious febrile illness in rural Southeast Asia. The causative agent, Orientia tsutsugamushi, is an obligate intracellular bacterium that is transmitted to humans by the bite of a Leptotrombidium mite. Research into the basic mechanisms of cell biology and pathogenicity of O. tsutsugamushi has lagged behind that of other important human pathogens. One reason for this is that O. tsutsugamushi is an obligate intracellular bacterium that can only be cultured in mammalian cells and that requires specific methodologies for propagation and analysis. Here, we have performed a body of work designed to improve methods for quantification, propagation, purification and long-term storage of this important but neglected human pathogen. These results will be useful to other researchers working on O. tsutsugamushi and also other obligate intracellular pathogens such as those in the Rickettsiales and Chlamydiales families.

Methodology

A clinical isolate of O. tsutsugamushi was grown in cultured mouse embryonic fibroblast (L929) cells. Bacterial growth was measured using an O. tsutsugamushi-specific qPCR assay. Conditions leading to improvements in viability and growth were monitored in terms of the effect on bacterial cell number after growth in cultured mammalian cells.

Key results

• Development of a standardised growth assay to quantify bacterial replication and viability in vitro.
• Quantitative comparison of different DNA extraction methods.
• Quantification of the effect on growth of FBS concentration, daunorubicin supplementation, media composition, host cell confluence at infection and frequency of media replacement.
• Optimisation of bacterial purification including a comparison of host cell lysis methods, purification temperature, bacterial yield calculations and bacterial pelleting at different centrifugation speeds.
• Quantification of bacterial viability loss after long term storage and freezing under a range of conditions including different freezing buffers and different rates of freezing.

Conclusions

Here we present a standardised method for comparing the viability of O. tsutsugamushi after purification, treatment and propagation under various conditions. Taken together, we present a body of data to support improved techniques for propagation, purification and storage of this organism. This data will be useful both for improving clinical isolation rates as well as performing in vitro cell biology experiments.     

The Effectiveness and Sustainability of a Universal School-Based Programme for Preventing Depression in Chinese Adolescents: A Follow-Up Study Using Quasi-Experimental Design

Background

A pilot study about the effectiveness of a universal school-based programme, “The Little Prince is Depressed”, for preventing depression in Chinese adolescents in Hong Kong was conducted and reported previously. This study used a larger sample to examine the effectiveness and sustainability of the programme.

Methods

This study used quasi-experimental design. Twelve schools enrolled in “The Little Prince is Depressed” programme either as an intervention or a control condition. The intervention schools carried out the 12-session programme in two phases: the professional-led first phase and the teacher-led second phase. All participants were required to complete a questionnaire at three time points measuring their (1) depressive, anxiety, and stress levels; (2) knowledge of mental health; (3) attitudes towards mental illness; (4) perceived social support; and (5) help-seeking behaviours.

Results

A total of 3,391 students participated in the study. The level of depressive symptoms did not reduce significantly at post-intervention; however, a delayed effect was observed at follow-up assessment for the participants of the teacher-led group in reducing anxiety and stress levels. Also, the knowledge of mental health and attitudes towards mental illness of the intervention-group participants significantly improved at post-test, and the outcomes were maintained at 4 to 5 months after the intervention in both the professional-led and the teacher-led conditions (p<.05). A preference among schoolchildren for whom to seek help from was identified.

Conclusions

The universal depression prevention programme was effective in enhancing knowledge of mental health and promoting a more positive attitude towards mental illness among adolescents in Hong Kong. In particular, the teacher-led group showed better outcomes than the professional-led group in reducing students’ anxiety and stress at follow-up period. The programme can achieve sustainability in schools if teachers are provided with adequate support.     

Integration of Social,Cultural, and Biomedical Strategies into an Existing Couple-Based Behavioral HIV/STI Prevention Intervention: Voices of Latino Male Couples

Introduction

Successful HIV prevention and treatment requires evidence-based approaches that combine biomedical strategies with behavioral interventions that are socially and culturally appropriate for the population or community being prioritized. Although there has been a push for a combination approach, how best to integrate different strategies into existing behavioral HIV prevention interventions remains unclear. The need to develop effective combination approaches is of particular importance for men who have sex with men (MSM), who face a disproportionately high risk of HIV acquisition.

Materials and Methods

We collaborated with Latino male couples and providers to adapt Connect ‘n Unite, an evidence-based intervention for Black male couples, for Latino male couples. We conducted a series of three focus groups, each with two cohorts of couples, and one focus group with providers. A purposive stratified sample of 20 couples (N = 40, divided into two cohorts) and 10 providers provided insights into how to adapt and integrate social, cultural, and biomedical approaches in a couples-based HIV/AIDS behavioral intervention.

Results

The majority (N = 37) of the couple participants had no prior knowledge of the following new biomedical strategies: non-occupational post-exposure prophylaxis (nPEP); pre-exposure prophylaxis (PrEP); and HIV self-testing kits. After they were introduced to these biomedical interventions, all participants expressed a need for information and empowerment through knowledge and awareness of these interventions. In particular, participants suggested that we provide PrEP and HIV self-testing kits by the middle or end of the intervention. Providers suggested a need to address behavioral, social and structural issues, such as language barriers; and the promotion of client-centered approaches to increase access to, adaptation of, and adherence to biomedical strategies. Corroborating what couple participants suggested, providers agreed that biomedical strategies should be offered after providing information about these tools. Regarding culturally sensitive and responsive approaches, participants identified stigma and discrimination associated with HIV and sexual identity as barriers to care, language barriers and documentation status as further barriers to care, the couple-based approach as ideal to health promotion, and the need to include family topics in the intervention.

Discussion

We successfully adapted an evidence-based behavioral HIV prevention intervention for Latino male couples. The adapted intervention, called Conectando Latinos en Pareja, integrates social, cultural, behavioral and biomedical strategies to address the HIV epidemic among Latino MSM. The study highlights the promise regarding the feasibility of implementing a combination approach to HIV prevention in this population.     

Effectiveness and Cost-Effectiveness of Occupation-Based Occupational Therapy Using the Aid for Decision Making in Occupation Choice (ADOC) for Older Residents: Pilot Cluster Randomized Controlled Trial

Background

Care-home residents are mostly inactive, have little interaction with staff, and are dependent on staff to engage in daily occupations. We recently developed an iPad application called the Aid for Decision-making in Occupation Choice (ADOC) to promote shared decision-making in activities and occupation-based goal setting by choosing from illustrations describing daily activities. This study aimed to evaluate if interventions based on occupation-based goal setting using the ADOC could focus on meaningful activities to improve quality of life and independent activities of daily living, with greater cost-effectiveness than an impairment-based approach as well as to evaluate the feasibility of conducting a large cluster, randomized controlled trial.

Method

In this single (assessor)-blind pilot cluster randomized controlled trial, the intervention group (ADOC group) received occupational therapy based on occupation-based goal setting using the ADOC, and the interventions were focused on meaningful occupations. The control group underwent an impairment-based approach focused on restoring capacities, without goal setting tools. In both groups, the 20-minute individualized intervention sessions were conducted twice a week for 4 months.

Main Outcome Measures

Short Form-36 (SF-36) score, SF-6D utility score, quality adjusted life years (QALY), Barthel Index, and total care cost.

Results

We randomized and analyzed 12 facilities (44 participants, 18.5% drop-out rate), with 6 facilities each allocated to the ADOC (n = 23) and control (n = 21) groups. After the 4-month intervention, the ADOC group had a significantly greater change in the BI score, with improved scores (P = 0.027, 95% CI 0.41 to 6.87, intracluster correlation coefficient = 0.14). No other outcome was significantly different. The incremental cost-effectiveness ratio, calculated using the change in BI score, was $63.1.

Conclusion

The results suggest that occupational therapy using the ADOC for older residents might be effective and cost-effective. We also found that conducting an RCT in the occupational therapy setting is feasible.

Trial Registration

UMIN Clinical Trials Registry UMIN000012994     

Which Dimensions of Patient-Centeredness Matter? - Results of a Web-Based Expert Delphi Survey

Background

Present models and definitions of patient-centeredness revealed a lack of conceptual clarity. Based on a prior systematic literature review, we developed an integrative model with 15 dimensions of patient-centeredness. The aims of this study were to 1) validate, and 2) prioritize these dimensions.

Method

A two-round web-based Delphi study was conducted. 297 international experts were invited to participate. In round one they were asked to 1) give an individual rating on a nine-point-scale on relevance and clarity of the dimensions, 2) add missing dimensions, and 3) prioritize the dimensions. In round two, experts received feedback about the results of round one and were asked to reflect and re-rate their own results. The cut-off for the validation of a dimension was a median < 7 on one of the criteria.

Results

105 experts participated in round one and 71 in round two. In round one, one new dimension was suggested and included for discussion in round two. In round two, this dimension did not reach sufficient ratings to be included in the model. Eleven dimensions reached a median ≥ 7 on both criteria (relevance and clarity). Four dimensions had a median < 7 on one or both criteria. The five dimensions rated as most important were: patient as a unique person, patient involvement in care, patient information, clinician-patient communication and patient empowerment.

Discussion

11 out of the 15 dimensions have been validated through experts’ ratings. Further research on the four dimensions that received insufficient ratings is recommended. The priority order of the dimensions can help researchers and clinicians to focus on the most important dimensions of patient-centeredness. Overall, the model provides a useful framework that can be used in the development of measures, interventions, and medical education curricula, as well as the adoption of a new perspective in health policy.