Community-engaged partnerships (community/academia/government) can play a role in developing effective protocols that address public health crises. Systemic racism, prioritization of money over humanity, and the repression of the local democratic processes through the State of Michigan Emergency Manager Law (Order of Act 439) all played a role in the Flint Water Crisis. Despite decades of collaboration between Flint-based community organizations and academic institutions, ways to navigate such crises and conduct relevant research were ineffective.

The Michigan Institute for Clinical and Health Research Community Engagement program at the University of Michigan and Flint’s Community Based Organization Partners co-developed the Research Readiness and Partnership Protocol (R2P2) to provide community-engaged recommendations that inform a rapid research response to public health emergencies. The R2P2 Workgroup conducted an extensive literature review and key interviews to inform protocol development.

This manuscript provides an overview of the Workgroup’s methods, key interview findings, and the main principles identified. Detailed recommendations and key elements to address prior to and during a crisis will be presented including methods for: establishing and maintaining trust, ensuring transparency, supporting clear communication, establishing a “front door” to academic institutions including a means to “sound the alarm,” addressing academic incentives, achieving equitable resource sharing, and addressing systemic racism.

This manuscript of community perspectives provides essential elements to develop meaningful community-academic research partnerships to address public health crises impacting communities, particularly communities of color. Furthermore, this work highlights an opportunity for greater acknowledgment and utilization of community-based participatory research (CBPR) by academic institutions.

Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.

We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).

At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.

Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.

283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.

Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).

PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.

Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.

The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and

relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).

APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).

Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.

To evaluate the uptake of universal vitamin D supplementation during pregnancy, its effectiveness in preventing vitamin D deficiency and the factors associated with these.

The regional public health organisation in Ayrshire, Scotland has a policy of universal provision of vitamin D supplements (10 µg/d) to all pregnant women for the duration of their pregnancy. Pregnant women in this area were recruited at their 12-week antenatal appointment. Blood samples were collected at the 12-week and 34-week appointments. To account for the seasonal variation, women were recruited in two cohorts: summer and winter. Telephone interviews were conducted at 34 weeks to assess the uptake of vitamin D supplements during pregnancy. Other variables were obtained from medical records.

The study was conducted in the NHS Ayrshire and Arran Health Board in Scotland.

612 pregnant women (aged 15–44 years) living in Ayrshire (latitude 55°), Scotland.

Sixty-six percentage took supplementation as recommended. Consumption of supplementation was significantly associated with a higher median serum 25-hydroxyvitamin D concentrations at 34 weeks. Despite this at 34 weeks, 33 % of the summer cohort had insufficient or deficient vitamin D status, while 15 % of the winter cohort had insufficient or deficient status. In multivariable analysis, only adherence and season were independent predictors of vitamin D status.

While supplementation improved and maintained vitamin D status during pregnancy, it was not adequate to ensure all those insufficient at 12 weeks achieved sufficient status at the end of pregnancy.

In 2017, the Michigan Institute for Clinical and Health Research (MICHR) and community partners in Flint, Michigan collaborated to launch a research funding program and evaluate the dynamics of those research partnerships receiving funding. While validated assessments for community-engaged research (CEnR) partnerships were available, the study team found none sufficiently relevant to conducting CEnR in the context of the work. MICHR faculty and staff along with community partners living and working in Flint used a community-based participatory research (CBPR) approach to develop and administer a locally relevant assessment of CEnR partnerships that were active in Flint in 2019 and 2021.

Surveys were administered each year to over a dozen partnerships funded by MICHR to evaluate how community and academic partners assessed the dynamics and impact of their study teams over time.

The results suggest that partners believed that their partnerships were engaging and highly impactful. Although many substantive differences between community and academic partners’ perceptions over time were identified, the most notable regarded the financial management of the partnerships.

This work contributes to the field of translational science by evaluating how the financial management of community-engaged health research partnerships in a locally relevant context of Flint can be associated with these teams’ scientific productivity and impact with national implications for CEnR. This work presents evaluation methods which can be used by clinical and translational research centers that strive to implement and measure their use of CBPR approaches.

Models estimate that the disability burden from mental disorders in Sub-Saharan Africa (SSA) will more than double in the next 40 years. Similar to HIV, mental disorders are stigmatized in many SSA settings and addressing them requires community engagement and long-term treatment. Yet, in contrast to HIV, the public mental healthcare cascade has not been sustained, despite robust data on scalable strategies. We draw on findings from our International AIDS Society (IAS) 2020 virtual workshop and make recommendations for next steps in the scale up of the SSA public mental healthcare continuum.

Early HIV surveillance and care cascade targets are discussed as important strategies for HIV response in SSA that should be adopted for mental health. Advocacy, including engagement with civil society, and targeted economic arguments to policymakers, are reviewed in the context of HIV success in SSA. Parallel opportunities for mental disorders are identified. Learning from HIV, communication of strategies that advance mental health care needs in SSA must be prioritized for broad global audiences.

The COVID-19 pandemic is setting off a colossal escalation of global mental health care needs, well-publicized across scientific, media, policymaker, and civil society domains. The pandemic highlights disparities in healthcare access and reinvigorates the push for universal coverage. Learning from HIV strategies, we must seize this historical moment to improve the public mental health care cascade in SSA and capitalize on the powerful alliances ready to be forged. As noted by Ambassador Goosby in our AIDS 2020 workshop, ‘The time is now’.

Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.

The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.

The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.

Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.

People aging with long-term physical disabilities (PAwLTPD), meaning individuals with onset of disability from birth through midlife, often require long-term support services (LTSS) to remain independence. The LTSS system is fragmented into aging and disability organizations with little communication between them. In addition, there are currently no evidence-based LTSS-type programs listed on the Administration for Community Living website that have been demonstrated to be effective for PAwLTPD. Because of these gaps, we have developed a community-based research network (CBRN), drawing on the practice-based research network model (PBRN), to bring together aging and disability organizations to address the lack of evidence-based programs for PAwLTPD.

Community-based organizations serving PAwLTPD across the state of Missouri were recruited to join the CBRN. A formative process evaluation of the network was conducted after a year to evaluate the effectiveness of the network.

Nine community-based organizations across the state of Missouri joined the CBRN. CBRN members include three centers for independent living (CILs), three area agencies on aging (AAAs), one CIL/AAA hybrid, one non-CIL disability organization, and one non-AAA aging organization. To date, we have held seven meetings, provided educational opportunities for CBRN members, and launched an inaugural research study within the CBRN. Formative evaluation data indicate that CBRN members feel that participation in the CBRN is beneficial.

The PBRN model appears to be a feasible framework for use with community-based organizations to facilitate communication between agencies and to support research aimed at addressing the needs of PAwLTPD.

Presenteeism, or working while ill, by healthcare personnel (HCP) experiencing influenza-like illness (ILI) puts patients and coworkers at risk. However, hospital policies and practices may not consistently facilitate HCP staying home when ill.

We conducted a mixed-methods survey in March 2018 of Emerging Infections Network infectious diseases physicians, describing institutional experiences with and policies for HCP working with ILI.

Of 715 physicians, 367 (51%) responded. Of 367, 135 (37%) were unaware of institutional policies. Of the remaining 232 respondents, 206 (89%) reported institutional policies regarding work restrictions for HCP with influenza or ILI, but only 145 (63%) said these were communicated at least annually. More than half of respondents (124, 53%) reported that adherence to work restrictions was not monitored or enforced. Work restrictions were most often not perceived to be enforced for physicians-in-training and attending physicians. Nearly all (223, 96%) reported that their facility tracked laboratory-confirmed influenza (LCI) in patients; 85 (37%) reported tracking ILI. For employees, 109 (47%) reported tracking of LCI and 53 (23%) reported tracking ILI. For independent physicians, not employed by the facility, 30 (13%) reported tracking LCI and 11 (5%) ILI.

More than one-third of respondents were unaware of whether their institutions had policies to prevent HCP with ILI from working; among those with knowledge of institutional policies, dissemination, monitoring, and enforcement of these policies was highly variable. Improving communication about work-restriction policies, as well as monitoring and enforcement, may help prevent the spread of infections from HCP to patients.

Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.

Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.

When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.

The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.

Commissioners of systematic reviews have differing requirements in terms of breadth of scope, level of analysis required, and timescales available. Planning a review requires consideration of the trade-off between these elements. This applies to both “rapid” reviews and “traditional” reviews with a broad or complex scope.

Approaches for tailoring review methods to commissioner requirements are described. These will be illustrated via case studies of reviews conducted for the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) and Health Services & Delivery Research (HS&DR) programs and other organizations.

An initial step is to discuss with commissioners the trade-off between timescales/resource available, breadth of review scope, and level of analysis; for example, broad overview of many studies or in-depth analysis of a narrower set. Where the evidence base is unknown, one option is to undertake an initial mapping review to assess the volume and type of evidence available. This may assist in refining the selection criteria for the main review, to prioritize the most relevant evidence. In complex reviews, a further option is to develop a conceptual model (logic model) with input from commissioners and experts, to help identify factors which may influence outcomes. This can enable design of focused mini-reviews (not necessarily exhaustive) around each factor. These methodological approaches will be illustrated through three case studies including an HTA on cannabis cessation (trade-off of breadth versus depth); a review of yoga and health (initial mapping to refine selection criteria); and a rapid review of congenital heart disease services (conceptual model to identify areas for focused reviews).

Different approaches may enable discussion with review commissioners around the trade-off between scope, methods and timescales, in order to tailor the review method to best meet commissioner requirements within the timescales available.

Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients.

This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman’s Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6–33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (−0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (−0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63–0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].

Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.

To determine macronutrients and micronutrients in foods served to and consumed by children at child-care centres in Oklahoma, USA and compare them with Dietary Reference Intakes (DRI).

Observed lunch nutrients compared with one-third of the age-based DRI (for 1–3 years-olds and 4–8-year-olds).

Oklahoma child-care centres (n 25), USA.

Children aged 3–5 years (n 415).

Regarding macronutrients, children were served 1782 (sd 686) kJ (426 (sd 164) kcal), 22·0 (sd 9·0) g protein, 51·5 (sd 20·4) g carbohydrate and 30·7 (sd 8·7) % total fat; they consumed 1305 (sd 669) kJ (312 (sd 160 kcal), 16·0 (sd 9·1) g protein, 37·6 (sd 18·5) g carbohydrate and 28·9 (sd 10·6) % total fat. For both age-based DRI: served energy (22–33 % of children), protein and carbohydrate exceeded; consumed energy (7–13 % of children) and protein exceeded, while carbohydrate was inadequate. Regarding micronutrients, for both age-based DRI: served Mg (65·9 (sd 24·7) mg), Zn (3·8 (sd 11·8) mg), vitamin A (249·9 (sd 228·3) μg) and folate (71·9 (sd 40·1) µg) exceeded; vitamin E (1·4 (sd 2·1) mg) was inadequate; served Fe (2·8 (sd 1·8) mg) exceeded only in 1–3-year-olds. Consumed folate (48·3 (sd 38·4) µg) met; Ca (259·4 (sd 146·2) mg) and Zn (2·3 (sd 3·0) mg) exceeded for 1–3-year-olds, but were inadequate for 4–8-year-olds. For both age-based DRI: consumed Fe (1·9 (sd 1·2) mg) and vitamin E (1·0 (sd 1·7) mg) were inadequate; Mg (47·2 (sd 21·8) mg) and vitamin A (155·0 (sd 126·5) µg) exceeded.

Lunch at child-care centres was twice the age-based DRI for consumed protein, while energy and carbohydrate were inadequate. Areas of improvement for micronutrients pertain to Fe and vitamin E for all children; Ca, Zn, vitamin E and folate for older pre-schoolers. Adequate nutrients are essential for development and the study reveals where public health nutrition experts, policy makers and care providers should focus to improve the nutrient density of foods.