The realities and expectations of community involvement in COVID-19 research: a Consumer Reference Group perspective.

BACKGROUND: Older adults have been disproportionately impacted by the COVID-19 pandemic. COVID-19 restrictions such as stay at home orders and physical distancing measures have been implemented to reduce older adults' risk of infection, however, such measures can have negative effects on older adults' mental health and social wellbeing. In 2020, the research team received funding as part of an Australian COVID-19 research grants program to investigate how services can better meet the mental health and social support needs of older adults during COVID-19. A Consumer Reference Group (CRG) was established to provide a community perspective on all research activities. MAIN BODY: The CRG comprised of eight older adults aged 65 years and older living in Western Australia. Two members of the CRG were involved in the initial grant proposal, and one member worked for a not-for-profit organisation that provides support and advocacy for older adults. The CRGs role was to provide consumer and community perspectives on the research design, advise on study materials, facilitate links between consumers, the community, and researchers, and advocate on behalf of consumers and the community. The CRG was encouraged to reflect on the research project, their contributions, and the outcomes obtained. In this commentary, we document the CRGs contributions to the project, and record their reflections, including what went well, what were some challenges, the realities of conducting research during COVID-19, and lessons learnt. CONCLUSION: The CRG were active participants in the research process. They shared their perspectives and made important contributions to the project. Through collaboration with the CRG, we were able to reach four key messages, underpinned by consumers lived experiences, that were used to co-develop knowledge translation products. These were disseminated to service providers and older adults.

Since the start of the COVID-19 pandemic, health and social measures have been introduced to reduce the spread of the virus, including lockdowns, physical distancing, and mask mandates. Older adults (aged 60 years and older) are considered particularly vulnerable to COVID-19 and have therefore faced some of the greatest restrictions to reduce their risk of infection. These restrictions can have a negative effect on older adults social and emotional wellbeing. In 2020 the research team received funding to investigate how services could better meet the mental health and social support needs of older Australians during the pandemic. To enable a community perspective on all research activities, a Consumer Reference Group (CRG) of eight older adults living in Western Australia was established. Two of the eight CRG members were involved in the initial grant proposal. The CRG's role was to share their thoughts on the research design, study materials, and to provide links to and advocate for consumers and the community. This commentary reports reflections from the CRC on what went well, what some of the challenges were, the realities of conducting this research during COVID-19, and what lessons were learnt. Through collaboration with the CRG key messages for the research project were reached and used to inform infographics, which were then disseminated to inform service delivery providers and older adults of the research outcomes.

Investigation of blood lead concentrations in dogs living in Flint, Michigan.

OBJECTIVE To measure blood lead concentrations (BLCs) in dogs living in Flint, Mich, following a declared water crisis and to assess potential associations of BLCs with demographic data, water sources, and clinical signs in these dogs. DESIGN Cross-sectional study. ANIMALS 284 dogs residing in Flint, Mich (test population), and 47 dogs residing in East Lansing, Mich (control population), and immediately adjacent areas. PROCEDURES Blood samples were collected at free screening clinics in Flint (test population) and at the Michigan State University College of Veterinary Medicine Veterinary Medical Center (control population). Owners of test population dogs completed questionnaires providing demographic and clinical information. Hematologic evaluations were performed; BLCs were measured by inductively coupled plasma-mass spectrometry. RESULTS 4 of 284 test population dogs had BLCs > 50 ppb; an additional 20 had BLCs > 20 ppb. Overall, BLCs of test population dogs were higher than those of control dogs. Within the test population, young dogs (≤ 2 years of age) had higher BLCs than old dogs (≥ 6 years of age). Only 7.2% of test population dogs were drinking unfiltered tap water at the time of screening; however, dogs that had been receiving filtered or bottled water for ≤ 3 months before screening had higher BLCs than did those that received such water for > 3 months. CONCLUSIONS AND CLINICAL RELEVANCE Taken together, findings suggested that the impact of the Flint water crisis extended to companion animals. Results highlighted the importance of maintaining awareness of lead exposure and considering both human and animal well-being in cases of environmental toxicant exposures.

The effect of age, sex, and rifampin administration on intestinal and hepatic cytochrome P450 3A activity.

BACKGROUND: The relative susceptibility of intestinal and hepatic cytochrome P450 (CYP) 3A to induction by rifampin (INN, rifampicin), as a function of age and sex, was investigated with the CYP3A substrate midazolam. METHODS: Fourteen young women (mean age, 26 +/- 4 years), 14 young men (mean age, 27 +/- 4 years), 14 elderly women (mean age, 72 +/- 5 years), and 10 elderly men (mean age, 70 +/- 4 years) received simultaneous intravenous doses (0.05 mg/kg over a 30-minute period) and oral doses of midazolam (3-8 mg of a stable isotope, (15)N(3)-midazolam) before and after 7 days of rifampin dosing (600 mg once daily in the evening). Serum and urine samples were assayed for midazolam, (15)N(3)-midazolam, and metabolites by liquid chromatography-mass spectrometry. RESULTS: No significant difference (P > or =.05) in the baseline systemic and oral clearance of midazolam was observed between male and female or young and old volunteers. Rifampin significantly (P <.0001) increased the systemic and oral clearance of midazolam from 0.44 +/- 0.2 L. h/kg and 1.56 +/- 0.8 L x h/kg to 0.96 +/- 0.3 L x h/kg and 34.4 +/- 21.2 L x h/kg, respectively. Likewise, the oral clearance of midazolam was significantly (P <.0001) increased in women and men, from 1.64 +/- 0.87 L x kg/h and 1.46 +/- 0.7 L x kg/h to 28.4 +/- 13.2 L x kg/h and 41.6 +/- 26.5 L x kg/h, respectively. A significant (P =.0023) effect of sex was noted in the extent of induction of the oral clearance of midazolam, being greater in men than in women. In contrast, the extent of midazolam systemic clearance induction was greater in women than in men (P =.0107). Age did not influence the extent of intestinal and hepatic CYP3A induction as determined by the oral and systemic clearance of midazolam. Rifampin dosing significantly (P <.0001) reduced the oral availability by 88%, from 0.32 +/- 0.13 to 0.04 +/- 0.02. Correspondingly, hepatic and intestinal availabilities were significantly (P <.0001) reduced after rifampin administration. After rifampin, the correlation coefficient for the relationship between oral availability and intestinal availability was significantly (P <.0001) reduced from 0.96 to 0.67, which reflects the increasing contribution of hepatic extraction to the determination of midazolam oral availability. A significant nonlinear inverse relationship was observed between the percent change in systemic clearance of midazolam and the initial baseline midazolam systemic clearance (r = -0.68, N = 52, P <.0001). Likewise, a significant inverse relationship was observed between the percent change in oral clearance and the baseline oral clearance (r = -0.39, N = 52, P =.0041). A significant inverse relationship between the ratio of hepatic intrinsic clearance in the presence of rifampin to that in the absence of rifampin and the corresponding ratio of intestinal intrinsic clearance was observed (Spearman correlation coefficient [r] = -0.68, P <.0001) and indicates that in a given individual the extent of induction was high at either the hepatic or the intestinal site but not both. CONCLUSION: Sex-related differences exist in the extent of intestinal and hepatic CYP3A induction by rifampin. The extent of induction at hepatic and intestinal sites was inversely dependent and reflected the independent regulation of CYP3A expression at these sites. The large interindividual variation in the extent of induction is explained in part by the variation in baseline expression of CYP3A. Sex-related differences in response to CYP3A inducers will be substrate-dependent and reflect the relative contribution of hepatic and intestinal sites of metabolism.

Evaluation of the implementation of an electronic medical record.

University of Minnesota Physicians, the faculty clinical practice organization of the Medical School, is implementing an Electronic Medical Record (EMR). During this process, we anticipated the need for an evaluative study of the implementation to examine process and satisfaction. This was in order to monitor the ability of the physicians to use the EMR effectively. The use of these data to evaluate the implementation and user-acceptance of change of process presents a unique research opportunity. The study of the impact of the EMR implementation on patient care, education, and other issues of academic interest make this research study valuable.

Induction of multidrug resistance-1 and cytochrome P450 mRNAs in human mononuclear cells by rifampin.

Reverse transcription-polymerase chain reaction (RT-PCR) and quantitative, competitive RT-PCR were used to examine the capability of rifampin to induce the expression of mRNA derived from multidrug resistance-1 (MDR1) and drug-metabolizing cytochrome P450 (P450) genes in the mononuclear fraction (lymphocytes) of human blood. A total of 50 healthy volunteers (age, 18-74) participated in two studies in which 600 mg of rifampin was administered orally once daily in the evening for 7 days. Twenty of these individuals also received fexofenadine before and after rifampin dosing. MDR1 and CYP2C8 mRNAs were expressed in 100% (50 of 50) and 95% (35 of 37) of individuals, respectively, at baseline. A significant (P < 0.05; n = 37) increase in the expression of MDR1 mRNA from 176,900 +/- 122,000 to 248,500 +/- 162,300 molecules/microg of RNA was observed following rifampin administration in the human lymphocytes. There was no significant (P > 0.05) difference in MDR1 mRNA expression between males and females at baseline. Interestingly, 58% of the individuals (n = 29) demonstrated a 120% increase [95% confidence interval (CI); 120%; range, 81-153%; responders] in MDR1 mRNA expression. In contrast, the remaining 42% of individuals (n = 21) exhibited a mean decrease of -5.2% (95% CI; -5.2%; range, -15 to +4%; nonresponders). Rifampin steady-state trough serum concentrations were not significantly different (P > 0.05) between responders and nonresponders. Likewise, there was no relationship between the observed induction in MDR1 mRNA expression in lymphocytes and the observed increase in fexofenadine oral clearance in twenty volunteers. The mRNA of CYP2E1, CYP3A5, CYP3A7, CYP4A11, and CYP4B1 genes were variably expressed at baseline and following rifampin treatment. In contrast, CYP2C9 and CYP3A4 mRNAs were undetectable in lymphocytes both before and after rifampin dosing. Interindividual variability in baseline expression and inducibility of MDR1 and P450 mRNA in human lymphocytes appeared to be substantial and may not reflect the expression of these enzymes in other tissues.