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Background Safe, highly curative, short course, direct acting antiviral (DAA) therapies are now available to treat chronic hepatitis C. DAA therapy is freely available to all adults chronically infected with the hepatitis C virus (HCV) in Australia. If left untreated, hepatitis C may lead to progressive hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Australia is committed to eliminating hepatitis as a public health threat by 2030 set by the World Health Organization. However, since the introduction of funded DAA treatment, uptake has been suboptimal. Australia needs improved strategies for testing, treatment uptake and treatment completion to address the persisting hepatitis C public health problem. PLATINUM C is a HCV treatment registry and research platform for assessing the comparative effectiveness of alternative interventions for achieving virological cure. Methods PLATINUM C will prospectively enrol people with active HCV infection confirmed by recent detection of HCV ribonucleic acid (RNA) in blood. Those enrolled will agree to allow standardised collection of demographic, lifestyle, treatment, virological outcome and other relevant clinical data to better inform the future management of HCV infection. The primary outcome is virological cure evidenced by sustained virological response (SVR), which is defined as a negative HCV PCR result 6 to 18 months after initial prescription of DAA therapy and no less than 12 weeks after the completion of treatment. Study participants will be invited to opt-in to medication adherence monitoring and quality of life assessments using validated self-reported instruments (EQ-5D-5L). Discussion PLATINUM C is a treatment registry and platform for nesting pragmatic trials. Data collected will inform the design, development and implementation of pragmatic trials. The digital infrastructure, study procedures and governing systems established by the registry will allow PLATINUM C to support a wider research platform in the management of hepatitis C in primary care. Trial registration The trial is registered with the Australia and New Zealand Clinical Trials Register (ACTRN12619000023156). Date of registration: 10/01/2019.

Background Atopic diseases are the most common chronic conditions of childhood. The apparent rise in food anaphylaxis in young children over the past three decades is of particular concern, owing to the lack of proven prevention strategies other than the timely introduction of peanut and egg. Due to reported in vitro differences in the immune response of young infants primed with whole-cell pertussis (wP) versus acellular pertussis (aP) vaccine, we systematically appraised and synthesised evidence on the safety and the potential allergy preventive benefits of wP, to inform recommendation for future practice and research. Objectives To assess the efficacy and safety of wP vaccinations in comparison to aP vaccinations in early infancy for the prevention of atopic diseases in children. Search methods We searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, and grey literature. The date of the search was 7 September 2020. Selection criteria We included randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) that reported the occurrence of atopic diseases, and RCTs only to assess safety outcomes. To be included studies had to have at least six months follow-up, and involve children under 18 years old, who received a first dose of either wP (experimental intervention) or aP (comparator) before six months of age. Data collection and analysis Two review authors independently screened studies for eligibility, extracted the data, and assessed risk of bias using standard Cochrane methods. We assessed the certainty of the evidence using GRADE. Our primary outcomes were diagnosis of IgE-mediated food allergy and all-cause serious adverse events (SAEs). Secondary outcomes included: diagnosis of not vaccine-associated anaphylaxis or urticaria, diagnosis of asthma, diagnosis of allergic rhinitis, diagnosis of atopic dermatitis and diagnosis of encephalopathy. Due to paucity of RCTs reporting on the atopic outcomes of interest, we assessed a broader outcome domain (cumulative incidence of atopic disease) as specified in our protocol. We summarised effect estimates as risk ratios (RR) and 95% confidence intervals (CI). Where appropriate, we pooled safety data in meta-analyses using fixed-effect Mantel-Haenszel methods, without zero-cell corrections for dichotomous outcomes. Main results We identified four eligible studies reporting on atopic outcomes, representing 7333 children. Based on a single trial, there was uncertain evidence on whether wP vaccines affected the risk of overall atopic disease (RR 0.85, 95% CI 0.62 to 1.17) or asthma only (RR 1.04, 95% CI 0.59 to 1.82; 497 children) by 2.5 years old.Three NRSIs were judged to be at serious or critical risk of bias due to confounding, missing data, or both, and were ineligible for inclusion in a narrative synthesis. We identified 21 eligible studies (137,281 children) that reported the safety outcomes of interest. We judged seven studies to be at high risk of bias and those remaining, at unclear risk. The pooled RR was 0.94 for all-cause SAEs (95% CI 0.78 to 1.15; I2 = 0%; 15 studies, 38,072 children). For every 1000 children primed with a first dose of wP, 11 had an SAE. The corresponding risk with aP was 12 children (95% CI 9 to 13). The 95% CI around the risk difference ranged from three fewer to two more events per 1000 children, and the certainty of the evidence was judged as moderate (downgraded one level for imprecision). No diagnoses of encephalopathy following vaccination were reported (95% CI around the risk difference - 5 to 12 per 100,000 children; seven primary series studies; 115,271 children). The certainty of the evidence was judged as low, since this is a serious condition, and we could not exclude a clinically meaningful difference. Authors' conclusions There is very low-certainty evidence that a first dose of wP given early in infancy, compared to a first dose of aP, affects the risk of atopic diseases in children. The incidence of all-cause SAEs in wP and aP vaccinees was low, and no cases of encephalopathy were reported. The certainty of the evidence was judged as moderate for all-cause SAEs, and low for encephalopathy. Future studies should use sensitive and specific endpoints of clinical relevance, and should be conducted in settings with high prevalence of IgE-mediated food allergy. Safety endpoints should prioritise common vaccine reactions, parental acceptability, SAEs and their potential relatedness to the dose administered.

The integrated behavioral health care model in primary care has the potential to reduce barriers to care experienced by children and families from ethnic minorities and low socioeconomic status. Limited access to pediatric behavioral health care is a significant problem, with up to 40% of children and adolescents with identified mental disorders and only 30% of them receiving care. Barriers include transportation, insurance, and shortage of specialists. Primary care provider bias, decreased knowledge and feelings of competence, and cultural beliefs and stigma also affect earlier diagnosis and treatment, particularly for Hispanic families with low English proficiency and African Americans.

BackgroundIncomplete vaccination in Australia is greatly due to vaccine hesitancy, which is driven by multiple factors. Studies analysing the effect of behavioural ‘nudges’ on vaccine uptake have shown promising results. Although there is some evidence for positively framed SMS vaccine messages, evidence is lacking for loss-based framed messages which may be highly effective but may paradoxically risk increasing vaccine hesitancy. This pilot study aimed to evaluate the effect of loss-based framed SMS messages on vaccine hesitancy.MethodsThis single-blinded randomised controlled trial enrolled pregnant women from antenatal clinics in King Edward Memorial Hospital, Perth, WA which delivers approximately 6000 higher-risk infants per year. Participants were randomised to receive either a loss-based framed SMS message warning of the risks of failure to vaccinate, or a sham SMS message unrelated to vaccination, and were asked to complete the short-scale vaccine hesitancy questionnaire before and after the intervention.DiscussionThe application of behavioural sciences through SMS-reminders has the potential to improve vaccination rates. There are difficulties in engaging with parents of newborns about vaccine hesitancy. Further research is warranted using other approaches to recruitment.HighlightsPilot randomised controlled trial on the use of SMS reminders to influence vaccine hesitancyApplication of behavioural economics, nudge techniques and mobile healthVaccine hesitancy measured using the short-scale PACV questionnaireThere are difficulties in engaging with parents of newborns about vaccine hesitancyFurther research needed to optimise message framing, timing and reduce vaccine hesitancyTrial RegistrationThe trial is registered with the Australia and New Zealand Clinical Trials Register (ACTRN12618001510235).

BackgroundIn the absence of an established gold standard, an understanding of the testing cycle from individual exposure to test outcome report is required to guide the correct interpretation of SARS-CoV-2 reverse transcriptase real-time polymerase chain reaction (RT-PCR) results and optimise the testing processes. Bayesian network (BN) models have been used within healthcare to bring clarity to complex problems. We use this modelling approach to construct a comprehensive framework for understanding the real world predictive value of individual RT-PCR results.MethodsWe elicited knowledge from domain experts to describe the test process from viral exposure to interpretation of the laboratory test, through a facilitated group workshop. A preliminary model was derived based on the elicited knowledge, then subsequently refined, parameterised and validated with a second workshop and one-on-one discussions.ResultsCausal relationships elicited describe the interactions of multiple variables and their impact on a RT-PCR result. Some interactions are infrequently observable and accounted for across the testing cycle such as pre-testing factors, sample collector experience and RT-PCR platform. By setting the input variables as ‘evidence’ for a given subject and preliminary parameterisation, three scenarios were simulated to demonstrate potential uses of the model.ConclusionsThe core value of this model is a deep understanding of the total testing cycle, bridging the gap between a person’s true infection status and their test outcome. This model can be adapted to different settings, testing modalities and pathogens, adding much needed nuance to the interpretations of results.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the efficacy and safety of whole‐cell pertussis (wP) vaccinations in comparison to acellular pertussis (aP) vaccinations in early infancy for the prevention of atopic diseases in children.

Heart disease is the leading cause of death in the United States. African Americans and people of low socioeconomic status suffer disproportionately from heart disease–related morbidity and mortality. In Detroit, Michigan, a primarily African American and low-income urban area, heart disease mortality is at twice the national rate. Despite evidence for the effectiveness of self-management support interventions in reducing chronic disease burden for older adults, few are adapted for communities most in need. This article describes the process of adapting Take PRIDE, an evidence-based heart disease self-management intervention, for older adults in Detroit via the Replicating Effective Programs (REP) framework. Working within a community–academic partnership, we found REP useful in facilitating the identification of diverse stakeholders, core versus adaptable elements of the intervention and barriers to implementation. We also made several modifications to the REP framework in order to better fit our project needs. Overall, we found REP to be an effective, flexible tool that allowed us to successfully adapt a disease-management intervention for this setting. Processes, lessons learned, and recommendations offered in this article may help researchers and practitioners working to expand access to self-management support for populations most affected by chronic disease.

Anxiety disorders are common in children and adolescents with reported prevalence rates between 10% and 30%. A combined approach to treatment has been found to be the most effective for optimal outcomes and is typically comprised of psychotherapy (especially exposure-based cognitive behavior therapy), family and patient education, and use of medication if indicated. In children and adolescents who might benefit from use of medications, selective serotonin reuptake inhibitors (SSRIs) are the drugs of choice. The safety and efficacy of medications other than SSRIs in the treatment of children and adolescents with anxiety disorders are not fully established. Most children and adolescents respond well to treatment with long lasting resolution of symptoms, although, recurrence of the same, or development of a different type of anxiety disorder, is not uncommon. In most children and adolescents, anxiety disorders tend to persist into adulthood requiring long-term treatment planning. This paper reviews the pharmacological agents used in the treatment of anxiety disorders in children and adolescents.

BackgroundFew published studies report lessons learned for recruiting older adults from racial/ethnic minority, low SES communities for behavioral interventions. In this article, we describe recruitment processes and results for Take Heart, a randomized controlled trial testing the effectiveness of an adapted heart disease self-management program for primarily African American, urban, low SES adults 50 years or older living in Detroit.MethodsOlder adults were recruited via community-based (CB), electronic medical record (EMR), and in-person hospital clinic (HC) methods. Recruitment processes, demographic characteristics of enrolled participants, yield and cost, lessons learned, and best practices for each method are described.ResultsWithin 22 months, 1,478 potential participants were identified, 1,223 were contacted and 453 enrolled, resulting in an overall recruitment yield of 37%. The CB method had the highest yield at 49%, followed by HC at 36% and EMR at 16%. Of six CB approaches, information sessions and flyers had the highest yields at 60% and 59%, respectively. The average cost of recruiting and enrolling one participant was $142.ConclusionsCB, EMR, and HC methods each made important contributions to reaching our recruitment goal. The CB method resulted in the highest recruitment yield, while EMR had the lowest. Face-to-face interaction with community members and hiring a community health worker were particularly useful in engaging this population. Further research is needed to confirm these findings in urban, minority, low SES populations of older adults.

Organic acids (OAs) are intermediary products of several amino acid catabolism or degradation via multiple biochemical pathways for energy production. Vitamins or co-factors are often quintessential elements in such degradation pathways and OA metabolism. OAs that result from enzyme defects in these pathways can be identified in body fluids utilizing gas chromatography-mass spectrometry techniques (GC/MS). OAs are silent contributor to acid base imbalance and can affect nitrogen balance and recycling. Since OA production occurs in distal steps of a specific amino acid catabolism, offending amino acid accumulation is not characteristic. OA disorders as inborn errors of metabolism (IEM) are included in differential diagnosis of metabolic acidosis, as the common mnemonic MUDPILES taught in medical schools. High anion gap metabolic acidosis with hyperammonemia is a characteristic OA biochemical finding. VOMIT (valine, odd chain fatty acids, methionine, isoleucine, and threonine) is a smart acronym and a common clinical presentation of OA disorders and can present as early life-threatening illness, prior to Newborn Screening results availability. Easy identification and available medical formula make the field of metabolic nutrition vital for management of OA disorders. Treatment strategies also involve cofactor/vitamin utilization to aid specific pathways and disorder management. Optimal metabolic control and regular monitoring is key to long-term management and prevention of morbidity, disability and mortality. Prompt utilization of acute illness protocol (AIP) or emergency protocol and disorder specific education of family members or caregivers, primary care physicians and local emergency health care facilities; cautiously addressing common childhood illnesses in patients with OA disorders, can help avoid poor short- and long-term morbidity, disability and mortality outcomes.

Aim: To present the methods and outcomes of stakeholder engagement in the development of interventions for children presenting to the emergency department (ED) for uncontrolled asthma. Methods: We engaged stakeholders (caregivers, physicians, nurses, administrators) from six EDs in a three-phase process to: define design requirements; prototype and refine; and evaluate. Results: Interviews among 28 stakeholders yielded themes regarding in-home asthma management practices and ED discharge experiences. Quantitative and qualitative evaluation showed strong preference for the new discharge tool over current tools. Conclusion: Engaging end-users in contextual inquiry resulted in CAPE (CHICAGO Action Plan after ED discharge), a new stakeholder-balanced discharge tool, which is being tested in a multicenter comparative effectiveness trial.

Non-Hispanic Black children in the US experience a higher prevalence of asthma and are more likely to have severe and poorly controlled asthma than their non-Hispanic White counterparts. These disparities are particularly pronounced among those living in public housing compared to the general population. To combat these disparities, health care researchers collaborated with public housing management to deliver a year-long community health worker (CHW) asthma and healthy homes intervention to children with asthma in six public housing developments. CHWs, hired from the targeted housing developments, educated families to better manage asthma medically and address asthma triggers in the home, and served as a bridge to medical, social, and public housing services. This is the first time such a full spectrum asthma intervention has been implemented by CHWs in public housing. Fifty-nine children completed the intervention, 95% of whom were African American. Daytime asthma symptoms in the previous two we...

OBJECTIVE: Coordinated Healthcare Interventions for Childhood Asthma Gaps in Outcomes (CHICAGO Plan) is a 3-arm multicenter pragmatic trial to evaluate asthma interventions in high-risk Chicago children presenting to Emergency Departments (ED) with asthma. A formative evaluation with end-users to provide input into the trial design and outcome instruments was conducted prior to trial initiation. METHODS: A multi-level data gathering framework from the field of design and standard qualitative methods were employed. This included one focus groups with asthma Community Health Workers (CHWs, N=8), two focus groups with caregivers of children with asthma (N=9), in-home interviews with caregivers (N=9), key informant interviews at six EDs and outpatient clinical sites (N=19), and ED tours and observations (N=6). Data were presented, discussed, and organized into themes. RESULTS: Data indicated that changes to the study design and discharge tool were warranted. A key insight was that ED discharge protocols typically place patient education at a single inopportune time, as families are preparing to leave the ED. At this point in time, families are less receptive to education due to fatigue and a desire to expedite the discharge process. The trial design was modified to reposition the discharge asthma plan to occur at earlier “teachable moments.” Delivery of the asthma discharge plan was assigned to study-employed ED coordinators instead of ED providers and staff. Other potential challenges to study recruitment and implementation were raised and addressed. CONCLUSIONS: Engagement of end-users in the design phase of implementation research is critical to improve research feasibility and relevance.

Many older adults with heart disease, especially those from vulnerable populations, live with chronic pain. Self-management strategies for reducing cardiovascular risk (e.g., physical activity, stress reduction) are also recommended for management of chronic pain. It is not known, however, whether self-management education focused on heart health has a beneficial “side effect” on pain-related outcomes. We explored this possibility using data from a randomized controlled trial (n=405) of Take Heart, a group intervention adapted for low-income, African American adults 50 and over with heart disease or significant risk factors. We first assessed the sample prevalence of high-impact chronic pain; i.e., substantial pain-related disability in one or more life domains (National Pain Strategy, 2016). Next, we assessed whether participation in Take Heart resulted in decreased pain interference (PROMIS-29). One-third of participants (n=131) met criteria for high impact chronic pain. Mean pain interference T-score in the entire sample at baseline was 58.1 (SD=9.9), indicating a score one standard deviation greater than population average. Compared to controls, intervention participants had a greater, but non-significant, improvement in pain interference (0.7 vs. -0.8; p=.11). Overall, findings demonstrate that African American adults with cardiovascular conditions have a high burden of comorbid pain. This pain was not greatly improved by an intervention that taught key chronic disease self-management skills but did not address pain specifically. Future research can test whether incorporating pain-management content into heart disease education has a stronger impact on improving pain outcomes -- which may, in turn, promote adherence to behaviors to reduce cardiovascular risk.

Asthma is a serious public health concern, disproportionately affecting urban, minority populations. Chicago’s West and Southwest sides are among the most burdened by asthma and environmental conditions that exacerbate asthma. Home-based, community health worker (CHW)–led interventions have repeatedly demonstrated effectiveness in addressing pediatric asthma. However, evidence of such interventions among adults is limited. Helping Chicago’s Westside Adults Breathe and Thrive is a longitudinal cohort study that assesses the effectiveness of a CHW-led asthma and healthy homes intervention for adults. One of the first of its kind, the program aims to improve asthma control and quality of life among adults with poorly controlled asthma. This article provides a framework for implementing the intervention from start to finish. CHWs make five or six home visits over the course of 12 months, providing comprehensive and individualized asthma education to study participants. They work closely with participants to conduct home environmental assessments, collaboratively developing techniques to eliminate or avoid asthma triggers. They also assist with smoking cessation, comorbidities, and health system navigation. Between December 1, 2013, and August 31, 2015, 202 participants enrolled in the program. This article reports on successes, challenges, and recommendations from the program’s first 21 months of operation.

Introduction The nicotinic α5 receptor subunit, encoded by CHRNA5, harbors multiple functional single nucleotide polymorphisms (SNPs) that affect mRNA expression and alter the encoded protein. These polymorphisms are most notably associated with drug-taking behaviors and cognition. We previously identified common SNPs in a distant regulatory element (DRE) that increase CHRNA5 mRNA expression in the human prefrontal cortex (PFC) and confer risk for nicotine dependence. Genome-wide epigenetic studies in PFC and adipose tissue find strong effects of the DRE SNPs on CpG methylation. However, it is unclear whether DRE SNPs influence CpG methylation en route to modulating CHRNA5 mRNA expression. It is also unclear whether these polymorphisms affect expression in other brain regions, especially those mediating drug-taking behaviors. Results By measuring total and allelic CHRNA5 mRNA expression in human habenula and putamen autopsy tissues, we found that CHRNA5 DRE variants considerably increase mRNA expression by up to 3.5-fold in both brain regions. Our epigenetic analysis finds no association between CpG methylation and CHRNA5 mRNA expression in the PFC or adipose tissues. Conclusions These finding suggests the mechanisms responsible for the genetic modulation of CpG methylation and mRNA expression are independent despite the DRE SNPs being highly associated with both measures. Our findings support a strong association between the DRE SNPs and mRNA expression or CpG methylation in the brain and periphery, but the independence of the two measures leads us to conclude that environmental factors affecting CpG methylation do not appear to directly modulate gene expression.