Measuring protective efficacy and quantifying the impact of drug resistance: A novel malaria chemoprevention trial design and methodology.

BACKGROUND: Recently revised WHO guidelines on malaria chemoprevention have opened the door to more tailored implementation. Countries face choices on whether to replace old drugs, target additional age groups, and adapt delivery schedules according to local drug resistance levels and malaria transmission patterns. Regular routine assessment of protective efficacy of chemoprevention is key. Here, we apply a novel modelling approach to aid the design and analysis of chemoprevention trials and generate measures of protection that can be applied across a range of transmission settings. METHODS AND FINDINGS: We developed a model of genotype-specific drug protection, which accounts for underlying risk of infection and circulating genotypes. Using a Bayesian framework, we fitted the model to multiple simulated scenarios to explore variations in study design, setting, and participant characteristics. We find that a placebo or control group with no drug protection is valuable but not always feasible. An alternative approach is a single-arm trial with an extended follow-up (>42 days), which allows measurement of the underlying infection risk after drug protection wanes, as long as transmission is relatively constant. We show that the currently recommended 28-day follow-up in a single-arm trial results in low precision of estimated 30-day chemoprevention efficacy and low power in determining genotype differences of 12 days in the duration of protection (power = 1.4%). Extending follow-up to 42 days increased precision and power (71.5%) in settings with constant transmission over this time period. However, in settings of unstable transmission, protective efficacy in a single-arm trial was overestimated by 24.3% if recruitment occurred during increasing transmission and underestimated by 15.8% when recruitment occurred during declining transmission. Protective efficacy was estimated with greater precision in high transmission settings, and power to detect differences by resistance genotype was lower in scenarios where the resistant genotype was either rare or too common. CONCLUSIONS: These findings have important implications for the current guidelines on chemoprevention efficacy studies and will be valuable for informing where these studies should be optimally placed. The results underscore the need for a comparator group in seasonal settings and provide evidence that the extension of follow-up in single-arm trials improves the accuracy of measures of protective efficacy in settings with more stable transmission. Extension of follow-up may pose logistical challenges to trial feasibility and associated costs. However, these studies may not need to be repeated multiple times, as the estimates of drug protection against different genotypes can be applied to different settings by adjusting for transmission intensity and frequency of resistance.

Uptake of screening and risk-reducing recommendations among women with hereditary breast and ovarian cancer syndrome due to pathogenic BRCA1/2 variants evaluated at a large urban comprehensive cancer center.

PURPOSE: Carriers of pathogenic variants in BRCA1/2 have an elevated lifetime cancer risk warranting high-risk screening and risk-reducing procedures for early detection and prevention. We report on prevention practices among women with pathogenic BRCA variants in order to document follow through with NCCN recommendations and to identify barriers to guideline-recommended care. METHODS: Our cohort included women who had genetic testing through a cancer genetic clinic and completed a 54-item questionnaire to measure socio-demographics, medical history, rates of cancer screening and risk-reducing surgery, disclosure of test results, and cancer worry. Outcomes included rates of completion of risk-reducing salpingo-oophorectomy (RRSO), risk-reducing mastectomy (RRM), and NCCN risk-reducing and age-dependent screening guidelines (version 3.2019). Multivariable logistic regression analyses were used to evaluate potential predictors of these outcomes. RESULTS: Of 129 evaluable women with pathogenic BRCA1/2 variants, 95 (74%) underwent RRSO and 77 (60%) had RRM, respectively, and 107 (83%) were considered adherent to NCCN guidelines. Women with a history of breast or ovarian cancer were more likely to have RRM (OR = 4.38; 95% CI 1.80-11.51; p = 0.002). Increasing age was associated with an increased likelihood of RRSO (OR = 1.05; 95% CI 1.01-1.09; p = 0.019) and decreased likelihood for RRM (OR = 0.95; 95% CI 0.92-0.99; p = 0.013). Women who had RRM were 3 times more likely to undergo RRSO (OR = 2.81; 95% CI 1.10-7.44; p = 0.025). Women who had genetic testing after June 2013 were less likely to have RRM than those tested before June 2013 (OR = 0.42; 95% CI 0.18-0.95; p = 0.040. None of the other measured factors were associated with rates of RRSO, RRM or follow through with NCCN recommendations. There was near universal (127/129) reported disclosure of genetic test results to family members, resulting in the discovery of a median of 1 relative with a pathogenic variant (range = 0-8). CONCLUSION: An evaluation of follow up practice in a cohort of women with pathogenic variants in BRCA1/2 revealed high rates of reported completion of screening and surgical risk-reducing recommendations. Educational efforts should continue to reinforce the importance of follow-through with guideline recommended care among this high-risk group.

Association between major discrimination and deficit accumulation in African American cancer survivors: The Detroit Research on Cancer Survivors Study.

BACKGROUND: Discrimination can adversely affect health and accelerate aging, but little is known about these relationships in cancer survivors. This study examines associations of discrimination and aging among self-identified African American survivors. METHODS: A population-based sample of 2232 survivors 20-79 years old at diagnosis were enrolled within 5 years of breast (n = 787), colorectal (n = 227), lung (n = 223), or prostate (n = 995) cancer between 2017 and 2022. Surveys were completed post-active therapy. A deficit accumulation index measured aging-related disease and function (score range, 0-1, where <0.20 is robust, 0.20 to <0.35 is pre-frail, and 0.35+ is frail; 0.06 is a large clinically meaningful difference). The discrimination scale assessed ever experiencing major discrimination and seven types of events (score, 0-7). Linear regression tested the association of discrimination and deficit accumulation, controlling for age, time from diagnosis, cancer type, stage and therapy, and sociodemographic variables. RESULTS: Survivors were an average of 62 years old (SD, 9.6), 63.2% reported ever experiencing major discrimination, with an average of 2.4 (SD, 1.7) types of discrimination events. Only 24.4% had deficit accumulation scores considered robust (mean score, 0.30 [SD, 0.13]). Among those who reported ever experiencing major discrimination, survivors with four to seven types of discrimination events (vs. 0-1) had a large, clinically meaningful increase in adjusted deficits (0.062, p < .001) and this pattern was consistent across cancer types. CONCLUSION: African American cancer survivors have high deficit accumulated index scores, and experiences of major discrimination were positively associated with these deficits. Future studies are needed to understand the intersectionality between aging, discrimination, and cancer survivorship among diverse populations.

Results of an African American-targeted norm-based colorectal cancer screening intervention: a pilot study.

Lower colorectal cancer screening rates among African Americans contribute to higher colorectal cancer incidence and mortality. We tested the effects of a racially-targeted messaging intervention that used favorable behavioral norm information to increase uptake of at-home Fecal Immunochemical Test (FIT) Kits. We expected stronger intervention effects among African Americans with stronger racial identity. Eligible African Americans were randomized to one of four intervention conditions: injunctive norm message, descriptive norm message, both messages, neither message. The norm-based messages were delivered via an animated video health message. Background variables, constructs defined by the theory of planned behavior, racial identity, screening modality preferences, and uptake and return of FIT Kits were assessed. Of 205 participants, 111(54%) requested FIT Kits. Contrary to hypotheses, multigroup path analyses indicated stronger effects of targeted messages among African Americans with weaker racial identity. Findings highlight the importance of within-race heterogeneity in the receptivity to racially-targeted health messages.

Medical mistrust, culturally targeted message framing, and colorectal cancer screening among African Americans.

Mistrust in the information and treatment provided by medical professionals and organizations hinders cancer screening among African Americans. However, its impact on responses to health messaging aimed at bolstering screening uptake is unknown. The present study examined the effects of medical mistrust on message framing and culturally targeted health messaging about colorectal cancer (CRC) screening. Screening eligible African Americans (N = 457) completed the Group-Based Medical Mistrust scale and then viewed an informational video about CRC risks, prevention, and screening, during which all participants received either a gain or loss-framed message about screening. Half of participants received an additional culturally targeted screening message. After messaging, all participants completed Theory of Planned Behavior measures of CRC screening receptivity, as well as items assessing expectations about experiencing racism when obtaining CRC screening (i.e., anticipatory racism). Hierarchical multiple regressions showed that medical mistrust predicted lower screening receptivity and greater anticipatory racism. Additionally, effects of health messaging were moderated by medical mistrust. Among participants high in mistrust, targeted messaging-regardless of message frame-bolstered normative beliefs about CRC. Additionally, only targeted loss-framed messaging bolstered attitudes toward CRC screening. Although targeted messaging reduced anticipatory racism among participants with high mistrust, anticipatory racism did not mediate messaging effects. Findings indicate medical mistrust may be an important culturally-relevant individual difference to attend to in addressing CRC screening disparities, including its potential to impact responses to cancer screening messaging.

Message Framing for Men? Gender Moderated Effects of Culturally Targeted Message Framing on Colorectal Cancer Screening Receptivity among African Americans.

Receptivity to recommended colorectal cancer (CRC) screening can be enhanced by use of loss-framed health messaging that emphasizes possible consequences of failing to act. However, a simultaneous use of culturally targeted messaging may be needed to achieve effectiveness when loss-framed messaging is used with African Americans, especially to reduce racism-related cognitions aroused by standard loss framing that impede CRC screening receptivity. This study considered whether effects of stand-alone and culturally targeted message framing on CRC screening receptivity differ between African American men and women. African Americans eligible for CRC screening (Men=117, Women=340) viewed an informational video about CRC risks, prevention, and screening, and were randomized to receive a gain or loss-framed message about screening. Half of participants received an additional culturally targeted message. Using the Theory of Planned Behavior, we measured receptivity to CRC screening. We also measured arousal of racism-related cognitions. A significant three-way interaction suggested effects of messaging on CRC screening receptivity were moderated by gender. Participants were no more receptive to CRC screening when standard loss-framing was used, but were more favorable if loss-framing was culturally targeted. However, these effects were more pronounced among African American men. Contrary to prior findings, gender moderated effects of culturally targeted loss-framed messaging were not attributable to reducing racism-related cognitions. Findings add to growing recognition of important nuance in effective use of message framing to also include gender, while suggesting a critical need to explore gender-relevant mechanistic pathways, potentially including how health messaging activates masculinity-related cognitions among African American men.

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

The impact of the COVID-19 pandemic on African American cancer survivors.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had profound effects on population health to date. African American cancer survivors are particularly vulnerable to developing severe consequences; therefore, understanding the impact of the virus on this patient population is critical. METHODS: The Detroit Research on Cancer Survivors cohort is a unique effort to understand the determinants of poor outcomes in African American cancer survivors. To date, more than 4500 cancer survivors and nearly 950 primary caregivers have been enrolled; participation includes a survey and the collection of biospecimens, medical records, and tumor tissue. Beginning in the spring of 2020, a supplemental survey focusing on the impact of COVID-19 was offered to enrolled participants. The analysis included 890 survivors. RESULTS: Nearly all survivors (>99%) reported changes in their daily activities in an effort to reduce the risk of infection. More than 40% of the survivors reported some disruption in their access to medical care. A substantial proportion of the survivors (>40%) reported feeling anxious, depressed, and/or isolated during the COVID-19 pandemic. Approximately 40% of the patients reported changes in health behaviors shown to negatively affect survivorship outcomes (physical inactivity, smoking, and alcohol use) as a result of the pandemic. CONCLUSIONS: The influence of the COVID-19 pandemic on African American cancer survivors is substantial: it has affected both their physical and mental health. Coupled with changes in health behaviors, these factors will likely affect outcomes in this high-risk patient population, and this makes further study and interventions necessary to mitigate the long-term impact of the pandemic on cancer outcomes.

Healthcare provider cultural competency and receptivity to colorectal cancer screening among African Americans.

African Americans suffer disproportionately from colorectal cancer (CRC), due in part to disparities in CRC screening. Better understanding culturally relevant psychosocial factors that impact CRC screening is therefore critical. This study examined how African Americans' perceived cultural competency of their physician is associated with receptivity to take-home stool-based CRC screening. CRC screening deficient African Americans (N = 457) completed a patient-focused measure of perceived cultural competency and watched a brief video about CRC risks, prevention, and screening. Receptivity to stool-based CRC screening was measured using Theory of Planned Behavior (TPB) constructs . Participants were also given an opportunity to receive a no-cost at-home Fecal Immunochemical Test (FIT) kit, and we measured acceptance of this offer as a behavioral outcome (yes-no). Results showed that perceived cultural competency was associated with higher receptive attitudes, more favorable norms, greater perceived behavioral control towards stool-based screening, and also greater intentions to engage in FIT Kit screening (p < 0.001). We also found significant indirect effects of perceived cultural competency on FIT kit uptake through intention-mediated pathways. This study provides crucial evidence that participants' perceived cultural competency may play an important role in preventive health behavior among racial minorities, including CRC screening uptake among African Americans.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Setting-specific Transmission Rates: A Systematic Review and Meta-analysis.

BACKGROUND: Understanding the drivers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is crucial for control policies, but evidence of transmission rates in different settings remains limited. METHODS: We conducted a systematic review to estimate secondary attack rates (SARs) and observed reproduction numbers (Robs) in different settings exploring differences by age, symptom status, and duration of exposure. To account for additional study heterogeneity, we employed a beta-binomial model to pool SARs across studies and a negative-binomial model to estimate Robs. RESULTS: Households showed the highest transmission rates, with a pooled SAR of 21.1% (95% confidence interval [CI]:17.4-24.8). SARs were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of ≤5 days. SARs related to contacts at social events with family and friends were higher than those for low-risk casual contacts (5.9% vs 1.2%). Estimates of SARs and Robs for asymptomatic index cases were approximately one-seventh, and for presymptomatic two-thirds of those for symptomatic index cases. We found some evidence for reduced transmission potential both from and to individuals younger than 20 years of age in the household context, which is more limited when examining all settings. CONCLUSIONS: Our results suggest that exposure in settings with familiar contacts increases SARS-CoV-2 transmission potential. Additionally, the differences observed in transmissibility by index case symptom status and duration of exposure have important implications for control strategies, such as contact tracing, testing, and rapid isolation of cases. There were limited data to explore transmission patterns in workplaces, schools, and care homes, highlighting the need for further research in such settings.

Xylazine detected in unregulated opioids and drug administration equipment in Toronto, Canada: clinical and social implications.

BACKGROUND: The North American opioid overdose crisis is driven in large part by the presence of unknown psychoactive adulterants in the dynamic, unregulated drug supply. We herein report the first detection of the psychoactive veterinary compound xylazine in Toronto, the largest urban center in Canada, by the city's drug checking service. METHODS: Toronto's Drug Checking Service launched in October 2019. Between then and February 2021, 2263 samples were submitted for analysis. The service is offered voluntarily at harm reduction agencies that include supervised consumption services. Samples were analyzed using gas chromatography-mass spectrometry or liquid chromatography-high resolution mass spectrometry. Targeted and/or untargeted screens for psychoactive substances were undertaken. RESULTS: In September 2020, xylazine was first detected by Toronto's Drug Checking Service. Among samples analyzed from September 2020 to February 2021 expected to contain fentanyl in isolation (610) or in combination with methamphetamine (16), xylazine was detected in 46 samples (7.2% and 12.5% of samples, respectively). Samples were predominantly drawn from used drug equipment. Three of the samples containing xylazine (6.5%) were associated with an overdose. CONCLUSION: We present the first detection of xylazine in Toronto, North America's fourth-largest metropolitan area. The increased risk of overdose associated with use of xylazine and its detection within our setting highlights the importance of drug checking services in supporting rapid responses to the emergence of potentially harmful adulterants. These data also highlight the clinical challenges presented by the dynamic nature of unregulated drug markets and the concomitant need to establish regulatory structures to reduce their contribution to overdose morbidity and mortality.

Promoting colonoscopy screening among low-income Latinos at average risk of colorectal cancer: A randomized clinical trial.

BACKGROUND: Screening colonoscopy (SC) for colorectal cancer (CRC) is underused by Latino individuals. The current randomized clinical trial examined the impact of 3 interventions: 1) patient navigation; 2) patient navigation plus standard Centers for Disease Control and Prevention print materials; and 3) patient navigation plus culturally targeted print materials for Latinos referred for SC. Demographic, personal and health history, and psychometric factors associated with SC also were examined. METHODS: A total of 344 urban Latino individuals aged 50 to 85 years with no personal and/or immediate family history of CRC diagnosed before age 60 years, no personal history of a gastrointestinal disorder, no colonoscopy within the past 5 years, with insurance coverage, and with a referral for SC were consented. Participants were randomized to patient navigation (20%), patient navigation plus standard Centers for Disease Control and Prevention print materials (40%), and patient navigation plus culturally targeted print materials (40%). The completion of SC was assessed at 12 months. RESULTS: The interventions had an overall SC rate of 82%. Counterintuitively, patients with an average income of <$10,000 were found to have higher SC rates (87%) than those with a greater income (75%). CONCLUSIONS: The addition of standard or culturally targeted print materials did not appear to increase SC rates above those for patient navigation. Indeed, after controlling for other variables, culturally targeted print materials were found to be associated with lower SC rates among Puerto Rican individuals.

Response to COVID-19 in South Korea and implications for lifting stringent interventions.

BACKGROUND: After experiencing a sharp growth in COVID-19 cases early in the pandemic, South Korea rapidly controlled transmission while implementing less stringent national social distancing measures than countries in Europe and the USA. This has led to substantial interest in their "test, trace, isolate" strategy. However, it is important to understand the epidemiological peculiarities of South Korea's outbreak and characterise their response before attempting to emulate these measures elsewhere. METHODS: We systematically extracted numbers of suspected cases tested, PCR-confirmed cases, deaths, isolated confirmed cases, and numbers of confirmed cases with an identified epidemiological link from publicly available data. We estimated the time-varying reproduction number, Rt, using an established Bayesian framework, and reviewed the package of interventions implemented by South Korea using our extracted data, plus published literature and government sources. RESULTS: We estimated that after the initial rapid growth in cases, Rt dropped below one in early April before increasing to a maximum of 1.94 (95%CrI, 1.64-2.27) in May following outbreaks in Seoul Metropolitan Region. By mid-June, Rt was back below one where it remained until the end of our study (July 13th). Despite less stringent "lockdown" measures, strong social distancing measures were implemented in high-incidence areas and studies measured a considerable national decrease in movement in late February. Testing the capacity was swiftly increased, and protocols were in place to isolate suspected and confirmed cases quickly; however, we could not estimate the delay to isolation using our data. Accounting for just 10% of cases, individual case-based contact tracing picked up a relatively minor proportion of total cases, with cluster investigations accounting for 66%. CONCLUSIONS: Whilst early adoption of testing and contact tracing is likely to be important for South Korea's successful outbreak control, other factors including regional implementation of strong social distancing measures likely also contributed. The high volume of testing and the low number of deaths suggest that South Korea experienced a small epidemic relative to other countries. Caution is needed in attempting to replicate the South Korean response in populations with larger more geographically widespread epidemics where finding, testing, and isolating cases that are linked to clusters may be more difficult.

Enablers and barriers for the provision of community-based HCV treatment: A case study of a real-world practice.

BACKGROUND: Although the availability of fully funded direct-acting antivirals (DAAs) and the eligibility of primary care providers (PCPs) to provide hepatitis C virus (HCV) have removed barriers related to access to hospital-based HCV treatment in Australia, there are still many barriers to the provision of HCV treatment in community settings. There is a lack of knowledge regarding the barriers to, and enablers of HCV treatment in community settings in Australia. This study aimed to identify barriers and enablers for the provision of community-based HCV treatment. METHODS: This study was a part of a mixed-method case study of the Cure-It programme. The programme was studied to better understand barriers and enablers experienced by stakeholders of such programmes. The programme is delivered through the Prince Charles Hospital in Brisbane, Australia, and aimed to improve access to HCV treatment in community settings. Data were collected using semi-structured interviews with 12 healthcare providers and nine patients between July and December 2018. Purposive sampling was used to ensure diverse views were captured. The interview transcripts were analysed using inductive thematic analysis. RESULTS: Ease of access to specialist support, easy and high value treatment, co-location with or providing other services and motivated patients enabled PCPs to be engaged with the Cure-It programme. Several interconnected factors related to patients' characteristics and health system acted synergistically to enable patients to initiate and complete treatment. These included a desire to remove HCV as a source of shame, having children, awareness of HCV consequences, access to DAAs for free, ease of access to general practices and drug and alcohol services, and access to a safe and enabling environment. The identified barriers were interconnected at the levels of patients, PCPs and primary care systems and acted synergistically to prevent patients and PCPs from becoming engaged with HCV treatment. PCPs' related barriers included a lack of knowledge, their perception of HCV as a specialist area and of patients with HCV as 'hard to manage' patients along with the practice preferences and priorities. Patients' related barriers included their socioeconomic characteristics, internalized stigma, perception of not being sick and lack of knowledge. Additionally, the unavailability of support for patients and existence of stigma in primary health care, along with poor communication between the hospital and primary care system, and the unavailability of FibroScan® in primary care discouraged PCPs and patients engagement specifically with the provision of community-based HCV treatment. CONCLUSION: Various strategies are needed to improve PCPs and patients' knowledge and awareness of HCV treatment. Training and support for PCPs need to be easy to access and should cover both clinical and social aspect of HCV. Connecting PCPs to other related services may improve PCPs' and patients' engagement with HCV treatment.

eHealth Activity among African American and White Cancer Survivors: A New Application of Theory.

eHealth is a promising resource for cancer survivors and may contribute to reducing racial disparities in cancer survivorship. This research applies the Unified Theory of Acceptance and Use of Technology (UTAUT) to examine eHealth activity among African American (AfAm) and White cancer survivors. In a population-based sample of AfAm and White survivors (n = 300), a Poisson regression tested whether UTAUT constructs (facilitating conditions, social influence, perceived ease of use, perceived usefulness) and beliefs about security/trustworthiness of eHealth were associated with the number of eHealth activities respondents had used. To test whether the effects varied across racial groups, interactions between each of these five facets and survivor race were included in the model. The model adjusted for demographic characteristics, cancer history, and internet access and use. Across racial groups, facilitating conditions (IRR = 1.44, 95%CI [1.17, 1.77]) and perceived usefulness (IRR = 1.16, 95%CI [1.08, 1.24]) were associated with increased eHealth activity. A marginally significant interaction between race and perceived ease of use (IRR = 1.17, 95%CI [0.99, 1.39]) indicated this perception was associated with decreased eHealth activity for White but not AfAm survivors. A significant interaction between race and perceived security/trustworthiness (IRR = 1.16, 95%CI [1.02, 1.32]) indicated this perception was associated with increased eHealth activity for AfAm but not White survivors. Social influence was not associated with eHealth use for either group (IRR = 1.07, 95%CI [0.98, 1.16]). Interventions targeting attitudes about eHealth may encourage its adoption and use. Furthermore, eHealth tools intended for use among AfAm cancer survivors should ensure they are secure and emphasize trustworthiness to intended users.

Outcomes of a tertiary-based innovative approach to engage primary care providers in provision of hepatitis C treatment in community settings.

BACKGROUND: Australia is committed to eliminating the hepatitis C virus (HCV) by 2030. Despite regulations in Australia that enable the prescription of subsidised direct acting antiviral (DAA) by primary health care providers, the number of providers who treat patients for HCV remains low and this limits the prospect of HCV elimination. The Prince Charles Hospital, Brisbane, Australia, implemented an innovative program called Cure-It aimed at engaging primary care providers in community-based HCV treatment. This paper aims to describe initial experiences and short-term patient outcomes of this program. METHODS: A formative evaluation was conducted using program data for the period March 2016 to April 2018. Descriptive statistics were used to report the number of engaged primary care providers, patients' baseline characteristics, treatment plans, and treatment outcomes. RESULTS: Thirty primary care providers from different settings were engaged in HCV treatment. Among 331 patients eligible for community-based treatment, 315 (95.2%) commenced treatment, the completion rate was 92.4 and 66.5% achieved sustained virological response at 12 weeks (SVR12). The SVR12 had not been documented for 26.8% of patients. Among patients whose SVR12 was documented, 98.2% achieved SVR12. Only 1.3% of patients experienced treatment failure. CONCLUSION: A flexible tertiary-led model can improve primary care providers and patients' engagement with provision of HCV treatment. Tertiary centres need to play their role to improve the accessibility of HCV treatment through providing training and on-going support for primary care providers while enabling those providers to become more confident in providing treatment independently.

Ubiquitous Yet Unclear: A Systematic Review of Medical Mistrust.

Peer-reviewed articles (n = 124) examining associations between medical mistrust (MM) and health outcomes from four databases, between January 1998 and May 2018, were reviewed; 36 qualitative and 88 quantitative studies met the inclusion criteria. The Williams and Mohammed framework guided our narrative synthesis of the studies; it argues that basic causes (e.g., biased institutions) affect the social status of marginalized groups which in turn effects multiple proximal pathways leading to responses and poor health. Most studies were cross-sectional with US-based samples. The MM in qualitative studies were categorized as interpersonal (n = 30), systemic (n = 22), and/or vicarious (n = 18); 25% did not explicitly note the basic causes of MM and race/ethnicity was often confounded with socioeconomic status (SES). All but three studies discussed an association between MM and a behavior response; no study focused on an actual health outcome. Most quantitative studies used multivariate regression analyses; only 15 of the 88 utilized advanced modeling techniques (e.g., mediation). Most (75%) studies did not describe basic causes for MM and 43% utilized low income samples. MM was conceptualized as a predictor/proximal pathway (in 73 studies) associated with a variety of responses, most commonly behavioral (e.g., diminished adherence); 14 studies found an association between MM and a specific health measure. This review underscores the need for future qualitative studies to place MM central to their research questions as in-depth descriptions of MM were limited. Future quantitative studies should replicate findings using more advanced analytical strategies that examine the relationship between MM and health outcomes.

Macro-environmental factors and physical activity in 28 European Union countries.

Data from the representative 2013 Eurobarometer survey were combined with macro-environmental data to assess relationships with different domains of physical activity (PA) in 28 European Union countries. Higher mean annual temperatures were the only macro-environmental factor found to be associated with levels of physical activity; an increase in the mean annual temperature by 1°C was associated with-0.94 fewer minutes of vigorous-intensity activity per week (95% CI: -1.66 to -0.23). This highlights the importance of modifiable influences (e.g. opportunities for active travel) on PA and underscores the potential of public health interventions to raise levels of physical activity.

Community-Based, Preclinical Patient Navigation for Colorectal Cancer Screening Among Older Black Men Recruited From Barbershops: The MISTER B Trial.

OBJECTIVES: To test the effectiveness of a preclinical, telephone-based patient navigation intervention to encourage colorectal cancer (CRC) screening among older Black men. METHODS: We conducted a 3-parallel-arm, randomized trial among 731 self-identified Black men recruited at barbershops between 2010 and 2013 in New York City. Participants had to be aged 50 years or older, not be up-to-date on CRC screening, have uncontrolled high blood pressure, and have a working telephone. We randomized participants to 1 of 3 groups: (1) patient navigation by a community health worker for CRC screening (PN), (2) motivational interviewing for blood pressure control by a trained counselor (MINT), or (3) both interventions (PLUS). We assessed CRC screening completion at 6-month follow-up. RESULTS: Intent-to-treat analysis revealed that participants in the navigation interventions were significantly more likely than those in the MINT-only group to be screened for CRC during the 6-month study period (17.5% of participants in PN, 17.8% in PLUS, 8.4% in MINT; P < .01). CONCLUSIONS: Telephone-based preclinical patient navigation has the potential to be effective for older Black men. Our results indicate the importance of community-based health interventions for improving health among minority men.

Uncultured Members of the Oral Microbiome.

Around one-third of oral bacteria cannot be cultured using conventional methods. Some bacteria have specific requirements for nutrients while others may be inhibited by substances in the culture media or produced by other bacteria. Oral bacteria have evolved as part of multispecies biofilms, and many thus require interaction with other bacterial species to grow. In vitro models have been developed that mimic these interactions and have been used to grow previously uncultivated organisms.