The Effect of HIV on the Association of Hyperglycaemia and Active Tuberculosis in Zambia, a Case-Control Study.

OBJECTIVES: To determine if HIV modifies the association between hyperglycaemia and active tuberculosis in Lusaka, Zambia. METHODS: A case-control study among newly-diagnosed adult tuberculosis cases and population controls in three areas of Lusaka. Hyperglycaemia is determined by random blood glucose (RBG) concentration measured at the time of recruitment; active tuberculosis disease by clinical diagnosis, and HIV status by serological result. Multivariable logistic regression is used to explore the primary association and effect modification by HIV. RESULTS: The prevalence of RBG concentration ≥ 11.1 mmol/L among 3843 tuberculosis cases was 1.4% and among 6977 controls was 1.5%. Overall, the adjusted odds ratio of active tuberculosis was 1.60 (95% CI 0.91-2.82) comparing those with RBG concentration ≥ 11.1- < 11.1 mmol/L. The corresponding adjusted odds ratio among those with and without HIV was 5.47 (95% CI 1.29-23.21) and 1.17 (95% CI 0.61-2.27) respectively; p-value for effect modification by HIV = 0.042. On subgroup analysis, the adjusted odds ratio of smear/Xpert-positive tuberculosis was 2.97 (95% CI 1.49-5.90) comparing RBG concentration ≥ 11.1- < 11.1 mmol/L. CONCLUSIONS: Overall, no evidence of association between hyperglycaemia and active tuberculosis was found, though among those with HIV and/or smear/Xpert-positive tuberculosis there was evidence of association. Differentiation of hyperglycaemia caused by diabetes mellitus and stress-induced hyperglycaemia secondary to tuberculosis infection is important for a better understanding of these findings.

Exploring ethnic differences in the distribution of blood test results in healthy adult populations to inform earlier cancer detection: a systematic review.

BACKGROUND: In primary care, health professionals use blood tests to investigate nonspecific presentations to inform referral decisions. Reference ranges for the commonly used blood tests in western countries were developed in predominately White populations, and so may perform differently when applied to non-White populations. Knowledge of ethnic variation in blood test results in healthy/general populations could help address ethnic inequalities in cancer referral for diagnosis and outcomes. OBJECTIVE: This systematic review explored evidence of ethnic differences in the distribution of selected blood test results among healthy/general populations to inform future research aimed at addressing inequalities in cancer diagnosis. METHODS: We searched PubMed and EMBASE to identify studies reporting measures of haemoglobin, MCV, calcium, albumin, platelet count, and CRP in nondiseased adults from at least 2 different ethnic groups. Two reviewers independently screened studies, completed data extraction and quality assessment using an adapted Newcastle-Ottawa scale. Participants were stratified into White, Black, Asian, Mixed, and Other groups. Data were synthesised narratively and meta-analyses were conducted where possible. RESULTS: A total of 47 papers were included. Black men and women have lower average values of haemoglobin, MCV, and albumin, and higher average values of CRP relative to their White counterparts. Additionally, Black men have lower average haemoglobin than Asian men, whereas Asian women have lower average CRP values when compared with White women. CONCLUSIONS: There is evidence of ethnic differences in average values of haemoglobin, MCV, CRP, and albumin in healthy/general populations. Further research is needed to explore the reasons for these differences. Systematic review registration: CRD42021274580.

Study protocol: Exploring the use of Family Health Histories in the African American community to reduce health disparities in Flint, Michigan.

Background: Health disparities are costly and preventable differences in disease progression that disproportionately affect minority communities such as African Americans. Practices to reduce health disparities can be rooted in prevention, particularly through screening tools. Family Health History tools are preventative screening mechanisms meant to explore family history to better understand how an individual's health can potentially be predicted or impacted. These tools are underutilized in the African American community. Contributions to this underutilization include a lack of cultural tailoring in the tools, a lack of health literacy in community members, and a lack of effective health communication. The Family Health History Study will create a culturally appropriate Family Health History toolkit to increase family health history utilization and ultimately decrease health disparities. Methods: The proposed sample will be composed of 195 African American adults ages 18 + who live in Genesee County, Michigan. The study consists of two phases: the development phase and the randomized pilot study phase. The goal of the development phase (n = 95) is to explore how Family Health History toolkits can be modified to better serve the African American community using a community based participatory research approach and to create a culturally tailored family health history toolkit. In the pilot study phase, 100 participants will be randomized to the culturally tailored toolkit or the current standard Family Health History toolkit. Outcomes will include feasibility and acceptability of the intervention. Discussion: This study will result in a culturally appropriate Family Health History tool that is co-developed with community members that can be utilized by African American adults to better understand their family health histories. Trial registration: Clinicaltrials.gov: NCT05358964 Date: May 5, 2022.

Effects of sex and hydration status on kappa opioid receptor-mediated diuresis in rats.

Understanding the function of the kappa opioid receptor (KOP) is crucial for the development of novel therapeutic interventions that target KOP for the treatment of pain, stress-related disorders and other indications. Activation of KOP produces diuretic effects in rodents and man. Sex is a vital factor to consider when assessing drug response in pre-clinical and clinical studies. In this study, the diuretic effect of the KOP agonist, U50488 (1-10 mg/kg), was investigated in both adult female and male Wistar rats that were either normally hydrated or water-loaded. The KOP antagonist norbinaltorphimine (norBNI, 10 mg/kg) was administered 24 h prior to U50488 to confirm the involvement of KOP. U50488 elicited a significant diuretic response at doses ≥ 3 mg/kg in both female and male rats independent of hydration status. U50488 diuretic effects were inhibited by norBNI pre-administration. Water-loading reduced data variability for urine volume in males, but not in females, compared with normally hydrated rats. Sex differences were also evident in U50488 eliciting a significant increase in sodium and potassium ion excretion only in males. This may suggest different mechanisms of U50488 diuretic action in males where renal excretion mechanisms are directly affected more than in females.

Taming the terminological tempest in invasion science.

Standardised terminology in science is important for clarity of interpretation and communication. In invasion science - a dynamic and rapidly evolving discipline - the proliferation of technical terminology has lacked a standardised framework for its development. The result is a convoluted and inconsistent usage of terminology, with various discrepancies in descriptions of damage and interventions. A standardised framework is therefore needed for a clear, universally applicable, and consistent terminology to promote more effective communication across researchers, stakeholders, and policymakers. Inconsistencies in terminology stem from the exponential increase in scientific publications on the patterns and processes of biological invasions authored by experts from various disciplines and countries since the 1990s, as well as publications by legislators and policymakers focusing on practical applications, regulations, and management of resources. Aligning and standardising terminology across stakeholders remains a challenge in invasion science. Here, we review and evaluate the multiple terms used in invasion science (e.g. 'non-native', 'alien', 'invasive' or 'invader', 'exotic', 'non-indigenous', 'naturalised', 'pest') to propose a more simplified and standardised terminology. The streamlined framework we propose and translate into 28 other languages is based on the terms (i) 'non-native', denoting species transported beyond their natural biogeographic range, (ii) 'established non-native', i.e. those non-native species that have established self-sustaining populations in their new location(s) in the wild, and (iii) 'invasive non-native' - populations of established non-native species that have recently spread or are spreading rapidly in their invaded range actively or passively with or without human mediation. We also highlight the importance of conceptualising 'spread' for classifying invasiveness and 'impact' for management. Finally, we propose a protocol for classifying populations based on (i) dispersal mechanism, (ii) species origin, (iii) population status, and (iv) impact. Collectively and without introducing new terminology, the framework that we present aims to facilitate effective communication and collaboration in invasion science and management of non-native species.

The Clinical Value of Pre-Diagnostic Thrombocytosis for the Detection of Lung Cancer in Primary Care.

Thrombocytosis is a risk marker for lung cancer in primary care. We investigated whether thrombocytosis presents pre-diagnostically for all the histological subtypes of lung cancer and its association with the stage at diagnosis. A matched cohort study used English electronic primary care data linked to the national cancer registry. Patients diagnosed with lung cancer aged ≥40 years with no prior history of malignancy were matched by age, sex, and general practice to five controls without lung cancer. Multivariable logistic regression models quantified the incidence of pre-diagnostic thrombocytosis and advanced-stage diagnoses, adjusting for COPD diagnosis, smoking status, and anti-platelet drug prescriptions. A total of 9504 cases were matched to 45,647 controls, consisting of 3260 (34%) adenocarcinomas (ADC), 2020 (21%) squamous cell carcinomas (SCC), 70 (<1%) large-cell carcinomas (LCC), and 1089 (12%) small-cell lung cancers (SCLC). The patients with lung cancer were 8.9 (95% CI 8.0-9.9) times more likely to exhibit pre-diagnostic thrombocytosis than the controls. The odds ratios were highest for the comparison between SCC and ADC (1.8, 95% CI 1.5-2.1). Thrombocytosis is associated with advanced-stage ADC and SCC but presented equally for early- and advanced-stage SCLC. Pre-diagnostic thrombocytosis may aid in the detection of all the histological subtypes in primary care.

Association between patient ethnicity and prostate cancer diagnosis following a prostate-specific antigen test: a cohort study of 730,000 men in primary care in the UK.

BACKGROUND: Black men have higher prostate-specific antigen (PSA) levels and higher prostate cancer incidence and mortality than White men, while Asian men tend to have lower prostate cancer incidence and mortality than White men. Much of the evidence comes from the USA, and information from UK populations is limited. METHODS: This retrospective cohort study used data on patients registered at general practices in England contributing to the Clinical Practice Research Datalink (CPRD) Aurum dataset. Those eligible were men aged 40 and over with a record of ethnicity and a PSA test result recorded between 2010 and 2017 with no prior cancer diagnosis. The aim was to assess the incidence of prostate cancer following a raised PSA test result in men from different ethnic groups. Additionally, incidence of advanced prostate cancer was investigated. Cancer incidence was estimated from multi-level logistic regression models adjusting for potential confounding factors. RESULTS: 730,515 men with a PSA test were included (88.9% White). Black men and men with mixed ethnicity had higher PSA values, particularly for those aged above 60 years. In the year following a raised PSA result (using age-specific thresholds), Black men had the highest prostate cancer incidence at 24.7% (95% CI 23.3%, 26.2%); Asian men had the lowest at 13.4% (12.2%, 14.7%); incidence for White men was 19.8% (19.4%, 20.2%). The peak incidence of prostate cancer for all groups was in men aged 70-79. Incidence of prostate cancer diagnosed at an advanced stage was similar between Black and White men. CONCLUSIONS: More prostate cancer was diagnosed in Black men with a raised PSA result, but rates of advanced prostate cancer were not higher in this group. In this large primary care-based cohort, the incidence of prostate cancer in men with elevated PSA levels increases with increasing age, even when using age-adjusted thresholds, with Black men significantly more likely to be diagnosed compared to White or Asian men. The incidence of advanced stage prostate cancer at diagnosis was similar for Black and White men with a raised PSA result, but lower for Asian men.

Validation of an adenosine triphosphate (ATP) model for 10-50 µm plankton.

A recent model demonstrated that the adenosine triphosphate (ATP) content of spherical aquatic organisms with a 10 to 50 µm diameter is between 0.16 and 19.9 pg cell-1. Here, the model is validated by comparing microscopy-based counts with ATP concentrations from a commercial ATP kit. The measured ATP content of both freshwater and marine organisms 10 to 50 µm size range falls in the 0.16 to 19.9 pg cell-1 model range. On average, freshwater organisms contain 0.33 pg ATP cell-1, have a spherical equivalent diameter (SED) of 13 µm, while marine organisms have 0.89 pg ATP cell-1 and a SED of 18 µm. In addition, their 13 to 18 µm size is within the 10 to 50 µm ballast water size range and in agreement with the 15 µm mean SED of a coastal plankton size-distribution model. This study concludes that the ATP-model is reliable, emphasizing the need for caution when converting three-dimensional biomass proxies into linear cell concentrations.

Use of the socio-ecological model to explore trusted sources of COVID-19 information in Black and Latinx communities in Michigan.

BACKGROUND: Identifying trusted sources of health information and exploring what makes these sources trustworthy is an important aspect of public health. This exploration requires embracing the cultural differences in minoritized communities, which are often treated as homogeneous. This qualitative study identifies and analyze the sources of trusted COVID-19 information among Black and Latinx communities in Michigan and assesses the rationale underlying this trust. METHODS: Interviews were conducted with 24 Black and 16 Latinx participants (n = 40) in four Michigan counties significantly impacted by COVID-19. The socio-ecological model was applied as an analytical framework for understanding the entities considered trusted sources of information. Within each level of the model, the dimensions of trustworthiness most salient for participants were identified. RESULTS: We found that sources of information came from all levels of the model, including interpersonal (COVID-19 survivors, church representatives, friends, relatives), organizational (employers, healthcare providers, traditional news reports), social media (hybrid source), community (members and groups), and public policy (county health department, federal and state government). Furthermore, participants determined whether they could trust information about COVID-19 by cross-referencing multiple resources. We identified competence, confidence, communication, and system trust as the dimensions of trustworthiness most often reported by participants. CONCLUSIONS: Our research suggests public health communications should engage in cross-referencing practices, providing information from sources at all levels of interaction, cultural competency, and awareness of historical/structural inequities. These efforts would be further strengthened by attending to needs for both factual information as well as care and personal connection.

Why local antibiotic resistance data matters - Informing empiric prescribing through local data collation, app design and engagement in Zambia.

BACKGROUND: Control of antimicrobial resistance (AMR) relies on local knowledge and local intervention implementation. Effective antibiotic stewardship requires locally-suitable prescribing guidelines. We aimed to use a novel digital tool (the ZARIApp) and a participatory approach to help develop locally-relevant empiric antibiotic prescribing guidelines for two hospitals in Lusaka, Zambia. METHODS: We produced an AMR report using samples collected locally and routinely from adults within the prior two years (April 2020 - April 2022). We developed the ZARIApp, which provides prescribing recommendations based on local resistance data and antibiotic prescribing practices. We used qualitative evaluation of focus group discussions among healthcare professionals to assess the feasibility and acceptability of using the ZARIApp and identify the barriers to and enablers of this stewardship approach. RESULTS: Resistance prevalence was high for many key pathogens: for example, 73% of 41 Escherichia coli isolates were resistant to ceftriaxone. We identified that high resistance rates were likely due to low levels of requesting and processing of microbiology samples from patients leading to insufficient and unrepresentative microbiology data. This emerged as the major barrier to generating locally-relevant guidelines. Through active stakeholder engagement, we modified the ZARIApp to better support users to generate empirical antibiotic guidelines within this context of unrepresentative microbiology data. Qualitative evaluation of focus group discussions suggested that the resulting ZARIApp was useful and easy to use. New antibiotic guidelines for key syndromes are now in place in the two study hospitals, but these have substantial residual uncertainty. CONCLUSIONS: Tools such as the free online ZARIApp can empower local settings to better understand and optimise how sampling and prescribing can help to improve patient care and reduce future AMR. However, the usability of the ZARIApp is severely limited by unrepresentative microbiology data; improved routine microbiology surveillance is vitally needed.

Correction: Community-Led, Cross-Sector Partnership of Housing and Health Care to Promote Aging in Place (Unite Health Project): Protocol for a Prospective Observational Study.

[This corrects the article DOI: 10.2196/47855.].

MICEAL Black and Latinx Perspectives on COVID-19 Vaccination: A Mixed-Methods Examination.

OBJECTIVES: To describe the differences and similarities in perceptions and attitudes regarding COVID-19 vaccination among Black and Latinx Michiganders. METHODS: Utilizing a convergent mixed-methods approach, forty interviews were conducted with 24 Black and 16 Latinx community members between December 2020 and June 2021 across four Michigan counties disproportionately affected by COVID-19. Survey data were collected from a representative sample of 1598 individuals living in Detroit between January and March 2021. RESULTS: Vaccine hesitancy was a more prevalent theme among Black interview participants than Latinx participants. Trust in experts and vaccine access were significantly more influential in the decision to vaccinate for Latinx residents compared to Black residents. Latinx individuals reported greater intention to receive a COVID-19 vaccine compared to Black respondents. Multinomial logit models revealed that 30% of Black participants expressed hesitancy about the COVID-19 vaccine compared to 10% of Latinx respondents. CONCLUSIONS AND IMPLICATIONS: This study provides a deeper understanding of key differences and similarities in vaccine acceptance/hesitancy across race/ethnicity. The findings can enhance health interventions and outcomes by informing the development of culturally responsive practices tailored to specific communities.

Sex Differences in Brain Region-Specific Activation of c-Fos following Kappa Opioid Receptor Stimulation or Acute Stress in Mice.

Kappa opioid receptors (KOPr) are involved in the response to stress. KOPr are also targets for the treatment of stress-related psychiatric disorders including depression, anxiety, and addiction although effects of KOPr are often sex-dependent. Here we investigated c-Fos expression in a range of brain regions in male and female mice following an acute stressor, and a single injection of KOPr agonist. Using adult C57BL/6 c-Fos-GFP transgenic mice and quantitative fluorescence microscopy, we identified brain regions activated in response to a challenge with the KOPr agonist U50,488 (20 mg/kg) or an acute stress (15 min forced swim stress, FSS). In male mice, U50,488 increased expression of c-Fos in the prelimbic area of the prefrontal cortex (PFCx), nucleus accumbens (NAcc), and basolateral nuclei of the amygdala (BLA). In contrast, in female mice U50,488 only activated the BLA but not the PFCx or the NAcc. FSS increased activation of PFCx, NAcc, and BLA in males while there was no activation of the PFCx in female mice. In both sexes, the KOPr antagonist norBNI significantly blocked U50,488-induced, but not stress-induced activation of brain regions. In separate experiments, activated cells were confirmed as non-GABAergic neurons in the PFCx and NAcc. Together these data demonstrate sex differences in activation of brain regions that are key components of the 'reward' circuitry. These differential responses may contribute to sex differences in stress-related psychiatric disorders and in the treatment of depression, anxiety, and addiction.

Colorectal cancer in symptomatic patients: How to improve the diagnostic pathway.

Even in countries with national screening programmes for colorectal cancer, most cancers are identified after the patient has developed symptoms. The patients present these symptoms usually to primary care, or in some countries to specialist care. In either healthcare setting, the clinician has to consider cancer to be a possibility, then to perform triage investigations, followed by definitive investigation, usually by colonoscopy. This apparently simple pathway is not simple: most symptoms of colorectal cancer are more likely to represent benign disease than cancer, and each of these stages represents selection of patients into a higher-risk pool. This article summarises a symptom-based approach to selection and initial investigation of such patients in primary care. Some special groups need particular attention, including the younger patient, those with an inherited predisposition to cancer, and those with co-morbidities.

Advancing Equity Through Centering Societal Values to Operationalize Racism as a Public Health Crisis: The KKey Values Inequities Model.

Background: The past two decades have been marked by increased efforts to advance equity in various disciplines, including social sciences, public health, environmental health, and medicine. In 2020, a national movement of municipalities declared racism a public health crisis. These efforts have coincided and likely shaped a growing sphere of federal and philanthropic funding for health equity, which frequently calls for practical interventions toward reducing and ultimately eliminating disparities. Disparities in health such as maternal mortality, infant mortality, diabetes, cancer, and stroke have been linked to root causes such as racism. Often, root causes are also linked to disparities in other sectors (i.e., finance/wealth attainment, educational attainment, career attainment, and home ownership). In 2021, in a study published in the New England Journal of Medicine, suggested that racist policies were root causes of U.S. racial health inequities. While racism, sexism, and classism, etc., are characterized as root causes, we posit that there is a deeper driver that has yet to be advanced. This presents a disparity-inequity model that maps disparities and inequities to the societal value system, not root causes. Methods: The KKey Values Inequities Disparities Model described in this article combines a case study of the Flint Water Crisis to explore the historic impact of human devaluation and its role in systemic racism and classism, which ultimately creates and exacerbates inequities that produce disparities in communities. The model integrates the value system and its contribution to societal causes (formerly known as root causes). Conclusions: A broadly defined values-inequities-disparities model will allow researchers, practitioners, decision makers, lawmakers, and community members to (1) assess the core root of inequities and disparities; (2) identify solutions in the human value domain; (3) design appropriate course corrective programming, interventions, processes, and procedures; and (4) create actions to integrate new systemic procedures and practices in our laws and governance to advance equity.

Association of the Stroke Ready Community-Based Participatory Research Intervention With Incidence of Acute Stroke Thrombolysis in Flint, Michigan.

Importance: Acute stroke treatment rates in the US lag behind those in other high-income nations. Objective: To assess whether a hospital emergency department (ED) and community intervention was associated with an increased proportion of patients with stroke receiving thrombolysis. Design, Setting, and Participants: This nonrandomized controlled trial of the Stroke Ready intervention took place in Flint, Michigan, from October 2017 to March 2020. Participants included adults living in the community. Data analysis was completed from July 2022 to May 2023. Intervention: Stroke Ready combined implementation science and community-based participatory research approaches. Acute stroke care was optimized in a safety-net ED, and then a community-wide, theory-based health behavior intervention, including peer-led workshops, mailers, and social media, was conducted. Main Outcomes and Measures: The prespecified primary outcome was the proportion of patients hospitalized with ischemic stroke or transient ischemic attack from Flint who received thrombolysis before and after the intervention. The association between thrombolysis and the Stroke Ready combined intervention, including the ED and community components, was estimated using logistic regression models, clustering at the hospital level and adjusting for time and stroke type. In prespecified secondary analyses, the ED and community intervention were explored separately, adjusting for hospital, time, and stroke type. Results: In total, 5970 people received in-person stroke preparedness workshops, corresponding to 9.7% of the adult population in Flint. There were 3327 ischemic stroke and TIA visits (1848 women [55.6%]; 1747 Black individuals [52.5%]; mean [SD] age, 67.8 [14.5] years) among patients from Flint seen in the relevant EDs, including 2305 in the preintervention period from July 2010 to September 2017 and 1022 in the postintervention period from October 2017 to March 2020. The proportion of thrombolysis usage increased from 4% in 2010 to 14% in 2020. The combined Stroke Ready intervention was not associated with thrombolysis use (adjusted odds ratio [OR], 1.13; 95% CI, 0.74-1.70; P = .58). The ED component was associated with an increase in thrombolysis use (adjusted OR, 1.63; 95% CI, 1.04-2.56; P = .03), but the community component was not (adjusted OR, 0.99; 95% CI, 0.96-1.01; P = .30). Conclusions and Relevance: This nonrandomized controlled trial found that a multilevel ED and community stroke preparedness intervention was not associated with increased thrombolysis treatments. The ED intervention was associated with increased thrombolysis usage, suggesting that implementation strategies in partnership with safety-net hospitals may increase thrombolysis usage. Trial Registration: ClinicalTrials.gov Identifier: NCT036455900.

Examining Community Engagement Research Strategies Used in Flint, Michigan: The Church Challenge.

BACKGROUND: The ways in which researchers may need to adapt traditional community-based participatory research engagement strategies during ongoing community trauma are understudied. We describe our efforts to engage the Flint, Michigan community in community-based participatory research in the aftermath of the Flint Water Crisis. OBJECTIVES: This manuscript describes 1) recruitment strategies selected before the Flint Water Crisis, 2) engagement lessons learned in the context of the Flint Water Crisis, and 3) barriers and facilitators encountered while engaging African American churches. METHODS: Researchers collaborated with community partners to engage and recruit a traumatized Flint community into the Church Challenge, a multilevel intervention to reduce chronic disease burden. LESSONS LEARNED: Recruitment and engagement strategies must be flexible, innovative, and may require nontraditional methods. CONCLUSIONS: Flexibility and adaptability are crucial for engaging with a traumatized community. Community-based participatory research work in traumatized communities must acknowledge and respond to community trauma to be successful.

Exploring Social Determinants of Health in Healthy Aging Among Older Adults: A Qualitative Study.

BACKGROUND: The U.S. population is aging and diversifying. Older Black Americans comprise the largest racial minority group and experience greater disability than White Americans. OBJECTIVES: Within a long-standing, community-based research partnership, we explored the determinants of healthy aging in Flint Michigan, a low-income, predominantly Black American community recovering from a water crisis. METHODS: Focus groups were conducted among older adults residing in Flint, Michigan. A grounded theory approach and constant comparison method was utilized for data analysis. RESULTS: Five focus groups were conducted with 49 total participants. We identified four themes that impacted healthy aging: economic instability, health care access and quality, neighborhood and built environment, and social and community context. Economic instability heavily influenced the other themes. CONCLUSIONS: Economic instability is a barrier to healthy aging. As a result, we are testing an innovative cross-sector partnership combining older adult affordable housing and health care.