Colorectal cancer risk stratification using a polygenic risk score in symptomatic primary care patients-a UK Biobank retrospective cohort study.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Accurate cancer risk assessment approaches could increase rates of early CRC diagnosis, improve health outcomes for patients and reduce pressure on diagnostic services. The faecal immunochemical test (FIT) for blood in stool is widely used in primary care to identify symptomatic patients with likely CRC. However, there is a 6-16% noncompliance rate with FIT in clinic and ~90% of patients over the symptomatic 10 µg/g test threshold do not have CRC. A polygenic risk score (PRS) quantifies an individual's genetic risk of a condition based on many common variants. Existing PRS for CRC have so far been used to stratify asymptomatic populations. We conducted a retrospective cohort study of 50,387 UK Biobank participants with a CRC symptom in their primary care record at age 40+. A PRS based on 201 variants, 5 genetic principal components and 22 other risk factors and markers for CRC were assessed for association with CRC diagnosis within 2 years of first symptom presentation using logistic regression. Associated variables were included in an integrated risk model and trained in 80% of the cohort to predict CRC diagnosis within 2 years. An integrated risk model combining PRS, age, sex, and patient-reported symptoms was predictive of CRC development in a testing cohort (receiver operating characteristic area under the curve, ROCAUC: 0.76, 95% confidence interval: 0.71-0.81). This model has the potential to improve early diagnosis of CRC, particularly in cases of patient noncompliance with FIT.

A high-density linkage map reveals broad- and fine-scale sex differences in recombination in the hihi (stitchbird; Notiomystis cincta).

Recombination, the process of DNA exchange between homologous chromosomes during meiosis, plays a major role in genomic diversity and evolutionary change. Variation in recombination rate is widespread despite recombination often being essential for progression of meiosis. One such variation is heterochiasmy, where recombination rates differ between sexes. Heterochiasmy has been observed across broad taxonomic groups, yet it remains an evolutionary enigma. We used Lep-MAP3, a pedigree-based software that is efficient in handling large datasets, to generate linkage maps for the hihi or stitchbird (Notiomystis cincta), utilising information from >36 K SNPs and 36 families. We constructed 29 linkage maps, including for the previously unscaffolded Z chromosome. The hihi is an endangered passerine endemic to Aotearoa New Zealand that is sexually dimorphic and exhibits high levels of sexual conflict, including sperm competition. Patterns in recombination in the hihi are consistent with those in other birds, including higher recombination rates in micro-chromosomes. Heterochiasmy in the hihi is male-biased, in line with predictions of the Haldane-Huxley rule, with the male linkage map being 15% longer. Micro-chromosomes exhibit heterochiasmy to a greater extent, contrary to that reported in other birds. At the intra-chromosomal level, heterochiasmy is higher nearer to chromosome ends and in gene-rich regions. Regions of extreme heterochiasmy are enriched for genes implicated in cell structure. This study adds an important contribution in assessing evolutionary theories of heterochiasmy and provides a framework for future studies investigating fine-scale heterochiasmy.

The diagnostic performance of CA-125 for the detection of ovarian cancer in women from different ethnic groups: a cohort study of English primary care data.

BACKGROUND: CA-125 testing is a recommended first line investigation for women presenting with possible symptoms of ovarian cancer in English primary care, to help determine whether further investigation for ovarian cancer is needed. It is currently not known how well the CA-125 test performs in ovarian cancer detection for patients from different ethnic groups. METHODS: A retrospective cohort study utilising English primary care data linked to the national cancer registry was undertaken. Women aged ≥ 40 years with a CA-125 test between 2010 and 2017 were included. Logistic regression predicted one-year ovarian cancer incidence by ethnicity, adjusting for age, deprivation status, and comorbidity score. The estimated incidence of ovarian cancer by CA-125 level was modelled for each ethnic group using restricted cubic splines. RESULTS: The diagnostic performance of CA-125 differed for women from different ethnicities. In an unadjusted analysis, predicted CA-125 levels for Asian and Black women were higher than White women at corresponding probabilities of ovarian cancer. The higher PPVs for White women compared to Asian or Black women were eliminated by inclusion of covariates. CONCLUSION: The introduction of ethnicity-specific thresholds may increase the specificity and PPVs of CA-125 in ovarian cancer detection at the expense of sensitivity, particularly for Asian and Black women. As such, we cannot recommend the use of ethnicity-specific thresholds for CA-125.

Isocitrate lyase promotes Puccinia striiformis f. sp. tritici susceptibility in wheat (Triticum aestivum) by suppressing accumulation of glyoxylate cycle intermediates.

Plant fungal parasites manipulate host metabolism to support their own survival. Among the many central metabolic pathways altered during infection, the glyoxylate cycle is frequently upregulated in both fungi and their host plants. Here, we examined the response of the glyoxylate cycle in bread wheat (Triticum aestivum) to infection by the obligate biotrophic fungal pathogen Puccinia striiformis f. sp. tritici (Pst). Gene expression analysis revealed that wheat genes encoding the two unique enzymes of the glyoxylate cycle, isocitrate lyase (TaICL) and malate synthase, diverged in their expression between susceptible and resistant Pst interactions. Focusing on TaICL, we determined that the TaICL B homoeolog is specifically upregulated during early stages of a successful Pst infection. Furthermore, disruption of the B homoeolog alone was sufficient to significantly perturb Pst disease progression. Indeed, Pst infection of the TaICL-B disruption mutant (TaICL-BY400*) was inhibited early during initial penetration, with the TaICL-BY400* line also accumulating high levels of malic acid, citric acid, and aconitic acid. Exogenous application of malic acid or aconitic acid also suppressed Pst infection, with trans-aconitic acid treatment having the most pronounced effect by decreasing fungal biomass 15-fold. Thus, enhanced TaICL-B expression during Pst infection may lower accumulation of malic acid and aconitic acid to promote Pst proliferation. As exogenous application of aconitic acid and malic acid has previously been shown to inhibit other critical pests and pathogens, we propose TaICL as a potential target for disruption in resistance breeding that could have wide-reaching protective benefits for wheat and beyond.

AssemblyQC: a Nextflow pipeline for reproducible reporting of assembly quality.

SUMMARY: Genome assembly projects have grown exponentially due to breakthroughs in sequencing technologies and assembly algorithms. Evaluating the quality of genome assemblies is critical to ensure the reliability of downstream analysis and interpretation. To fulfil this task, we have developed the AssemblyQC pipeline that performs file-format validation, contaminant checking, contiguity measurement, gene- and repeat-space completeness quantification, telomere inspection, taxonomic assignment, synteny alignment, scaffold examination through Hi-C contact-map visualization, and assessments of completeness, consensus quality and phasing through k-mer analysis. It produces a comprehensive HTML report with method descriptions, tables, and visualizations. AVAILABILITY AND IMPLEMENTATION: The pipeline uses Nextflow for workflow orchestration and adheres to the best-practice established by the nf-core community. This pipeline offers a reproducible, scalable, and portable method to assess the quality of genome assemblies-the code is available online at GitHub: https://github.com/Plant-Food-Research-Open/assemblyqc.

The effects of the first UK lockdown for the COVID-19 pandemic on primary-care-recorded cancer and type-2 diabetes mellitus records: A population-based quasi-experimental time series study.

BACKGROUND: COVID-19 disrupted consulting behaviour, healthcare delivery and cancer diagnostic services. This study quantifies the cancer incidence coded in UK general practice electronic health records and deviations from historical trends after the March 2020 national lockdown. For comparison, we study the coded incidence of type-2 diabetes mellitus, which is diagnosed almost entirely within primary care. METHODS: Poisson interrupted time series models investigated the coded incidence of diagnoses in adults aged ≥ 18 years in the Clinical Practice Research Datalink before (01/03/2017-29/02/2020) and after (01/03/2020-28/02/2022) the first lockdown. Datasets were stratified by age, sex, and general practice per 28-day aggregation period. Models captured incidence changes associated with lockdown, both immediately and over time based on historical trends. RESULTS: We studied 189,457 incident cancer and 191,915 incident diabetes records in 1480 general practices over 52,374,197 person-years at risk. During 01/03/2020-28/02/2022, there were fewer incident records of cancer (n = 22,199, 10.49 %, 10.44-10.53 %) and diabetes (n = 15,709, 7.57 %, 7.53-7.61 %) than expected. Within cancers, impacts ranged from no effect (e.g. unknown primary, pancreas, and ovary), to small effects for lung (n = 773, 3.11 %, 3.09-3.13 % fewer records) and female breast (n = 2686, 6.77 %, 6.73-6.81 %), to the greatest effect for bladder (n = 2874, 31.15 %, 31.00-31.31 %). Diabetes and cancer records recovered maximally to 86 % (95 %CI 80.3-92.7 %) and 74 % (95 %CI 70.3-78.6 %) in July 2021 and May 2021, respectively, of their expected values, declining again until the study end. CONCLUSION: The "missing" cancer and diabetes diagnoses in primary care may comprise delayed or missed diagnoses, reduced incidence associated with excess deaths from COVID-19, and potentially increased non-coded recording of diagnoses. Future validation studies must quantify the concordance between primary care and National Cancer Registration Data and Hospital Episode Statistics over the pandemic era.

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.

Exploring the Acceptability and Feasibility of Remote Blood Pressure Measurements and Cognition Assessments Among Participants Recruited From a Safety-Net Emergency Department (Reach Out Cognition): Nonrandomized Mobile Health Trial.

BACKGROUND: Hypertension is a prevalent cardiovascular risk factor disproportionately affecting Black Americans, who also experience a higher incidence of Alzheimer disease and Alzheimer disease-related dementias. Monitoring blood pressure (BP) and cognition may be important strategies in reducing these disparities. OBJECTIVE: The objective of the Reach Out Cognition study was to explore the feasibility and acceptability of remote cognitive and BP assessments in a predominantly Black, low-income population. METHODS: Reach Out was a randomized, controlled, mobile health-based clinical trial to reduce BP among patients with hypertension at an emergency department in a safety-net hospital (ie, a US hospital in which 25% of the patients are Medicaid recipients). Upon conclusion of Reach Out, participants were given the option of continuing into an extension phase, Reach Out Cognition, that included Bluetooth-enabled BP monitoring and digital cognitive assessments for 6 months. Digital cognitive assessments were text message-linked online surveys of the Self-Administered Gerocognitive Exam and Quality of Life in Neurological Disorders scale. BP assessments were measured with Bluetooth-enabled BP cuffs paired with an app and the data were manually sent to the research team. Outcomes were feasibility (ie, enrollment and 3- and 6-month completion of digital cognitive and BP assessments) and acceptability of assessments using a 4-item validated survey, ranging from 1 (not acceptable) to 5 (completely acceptable). RESULTS: Of the 211 Reach Out participants, 107 (50.7%) consented and 71 (33.6%) completed enrollment in Reach Out Cognition. Participants had a mean age of 49.9 years; 70.4% were female and 57.8% identified as Black. Among the 71 participants, 51 (72%) completed cognitive assessments at 3 months and 34 (48%) completed these assessments at 6 months. BP assessments were completed by 37 (52%) and 20 (28%) of the 71 participants at 3 and 6 months, respectively. Participants were neutral on the acceptability of the digital cognitive assessments (mean 3.7) and Bluetooth self-measured BP (SMBP) monitoring (mean 3.9). Participants noted challenges syncing the BP cuff to the app, internet connection, and transmitting the data to the research team. CONCLUSIONS: Enrollment and assessment completion were low, while acceptability was moderate. Technological advances will eliminate some of the Bluetooth SMBP barriers and offer new strategies for cognitive assessments. Subsequent studies could benefit from offering more comprehensive support to overcome Bluetooth-related hurdles, such as personalized training materials, video conferencing, or in-person research team support. Alternatively, strategies that do not require pairing with an app and passive transmission of data could be considered. Overall, further research is warranted to optimize participant engagement and overcome technological challenges. TRIAL REGISTRATION: ClinicalTrials.gov NCT03422718; https://clinicaltrials.gov/study/NCT03422718.

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.

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.

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.

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.

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.].

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.