Antinociceptive and adverse effects of morphine:ketamine mixtures in rats.

Prescription opioids are the gold standard for treating moderate to severe pain despite their well-documented adverse effects. Of all prescription medications, opioids are abused most widely, and fatal overdoses have reached epidemic levels. One strategy for improving the margin of safety of opioids is combining them with non-opioid drugs to decrease the opioid dose needed for pain relief, thereby reducing adverse effects that occur with larger doses. The N-methyl-D-aspartate receptor antagonist ketamine has been used safely as an analgesic but only under a very limited range of conditions. The current studies characterized the antinociceptive, behavioral suppressant, and gastrointestinal effects of morphine and ketamine alone and in mixtures to determine their interaction in 24 adult male Sprague-Dawley rats (n = 8 per assay). Given alone, both morphine and ketamine produced antinociception, decreased responding for food, and reduced gastrointestinal transit (i.e. produced constipation). The effects of morphine:ketamine mixtures generally were additive, except for the antinociceptive effects of 1:1 mixtures for which the difference in slope (i.e. non-parallel shift) between the observed and predicted effects suggested synergy at smaller doses and additivity at larger doses. The potency of morphine to produce constipation was not enhanced by administration of morphine:ketamine mixtures with antinociceptive effects. The nature of the interaction between morphine and ketamine for adverse effects such as dependence, withdrawal, abuse, or respiratory depression remains unknown but also might be related to the ratio of each drug in mixtures. It will be important to identify conditions that produce the largest potential therapeutic window in humans.

Ceftaroline for Central Nervous System Infections: Case Report of a Young Infant, and Scoping Review.

BACKGROUND: Managing health care acquired and device-associated intracranial infections in young children can be challenging given adverse antibiotic side effects and difficulties in achieving adequate central nervous system (CNS) antibiotic concentrations. Ceftaroline is a cephalosporin with a favorable safety profile and activity against methicillin-resistant Staphylococci and several Gram-negative organisms. Published data on the use of ceftaroline for CNS infections in children and adults are limited. METHODS: We describe a 2-month-old infant with ventriculo-subgaleal shunt-associated methicillin-resistant Staphylococcus epidermidis ventriculitis, which was successfully treated with ceftaroline, in addition to vancomycin and rifampin. We conducted a scoping review of English-language literature retrieved from PubMed, EMBASE and Web of Science that assessed the use of ceftaroline for CNS infections. RESULTS: We identified 22 articles for inclusion in our review, which described 92 unique patients, of whom 2 were <21 years old. Ceftaroline was commonly used in conjunction with other antibiotics to treat infections caused by Staphylococcus aureus, coagulase-negative Staphylococci and Streptococcus pneumoniae. Most case reports described clinical success with ceftaroline, though small case series and cohort studies yielded mixed efficacy assessments. Adverse effects attributed to ceftaroline were rare and included reversible myelosuppression, eosinophilia, hepatotoxicity and nephrotoxicity. Pharmacokinetic/pharmacodynamic studies suggested similar CNS penetration through inflamed meninges as other beta lactam antibiotics. CONCLUSIONS: We identified a growing body of published evidence supporting the use of ceftaroline in combination with other agents for the treatment of CNS infections. In absence of clinical trials, additional real-world data are needed to define the efficacy and safety of ceftaroline for children and adults with CNS infections.

Neuroprotective efficacy of hypothermia and Inter-alpha Inhibitor Proteins after hypoxic ischemic brain injury in neonatal rats.

Therapeutic hypothermia is the standard of care for hypoxic-ischemic (HI) encephalopathy. Inter-alpha Inhibitor Proteins (IAIPs) attenuate brain injury after HI in neonatal rats. Human (h) IAIPs (60 â€‹mg/kg) or placebo (PL) were given 15 â€‹min, 24 and 48 â€‹h to postnatal (P) day-7 rats after carotid ligation and 8% oxygen for 90 â€‹min with (30 â€‹°C) and without (36 â€‹°C) exposure to hypothermia 1.5 â€‹h after HI for 3 â€‹h. Hemispheric volume atrophy (P14) and neurobehavioral tests including righting reflex (P8-P10), small open field (P13-P14), and negative geotaxis (P14) were determined. Hemispheric volume atrophy in males was reduced (P â€‹< â€‹0.05) by 41.9% in the normothermic-IAIP and 28.1% in the hypothermic-IAIP compared with the normothermic-PL group, and in females reduced (P â€‹< â€‹0.05) by 30.3% in the normothermic-IAIP, 45.7% in hypothermic-PL, and 55.2% in hypothermic-IAIP compared with the normothermic-PL group after HI. Hypothermia improved (P â€‹< â€‹0.05) the neuroprotective effects of hIAIPs in females. The neuroprotective efficacy of hIAIPs was comparable to hypothermia in female rats (P â€‹= â€‹0.183). Treatment with hIAIPs, hypothermia, and hIAIPs with hypothermia decreased (P â€‹< â€‹0.05) the latency to enter the peripheral zone in the small open field test in males. We conclude that hIAIPs provide neuroprotection from HI brain injury that is comparable to the protection by hypothermia, hypothermia increases the effects of hIAIPs in females, and hIAIPs and hypothermia exhibit some sex-related differential effects.

Longitudinal prognosis of Parkinson's outcomes using causal connectivity.

Despite the prevalence of Parkinson's disease (PD), there are no clinically-accepted neuroimaging biomarkers to predict the trajectory of motor or cognitive decline or differentiate Parkinson's disease from atypical progressive parkinsonian diseases. Since abnormal connectivity in the motor circuit and basal ganglia have been previously shown as early markers of neurodegeneration, we hypothesize that patterns of interregional connectivity could be useful to form patient-specific predictive models of disease state and of PD progression. We use fMRI data from subjects with Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), idiopathic PD, and healthy controls to construct predictive models for motor and cognitive decline and differentiate between the four subgroups. Further, we identify the specific connections most informative for progression and diagnosis. When predicting the one-year progression in the MDS-UPDRS-III1* and Montreal Cognitive assessment (MoCA), we achieve new state-of-the-art mean absolute error performance. Additionally, the balanced accuracy we achieve in the diagnosis of PD, MSA, PSP, versus healthy controls surpasses that attained in most clinics, underscoring the relevance of the brain connectivity features. Our models reveal the connectivity between deep nuclei, motor regions, and the thalamus as the most important for prediction. Collectively these results demonstrate the potential of fMRI connectivity as a prognostic biomarker for PD and increase our understanding of this disease.

SARS-Cov-2 small viral RNA suppresses gene expression via complementary binding to mRNA 3' UTR.

SARS-CoV-2 (SC2) has been intensely studied since its emergence. However, the mechanisms of host immune dysregulation triggered by SC2 remain poorly understood. That said, it is well established that many prominent viral families encode microRNAs (miRNAs) or related small viral RNAs (svRNAs) capable of regulating human genes involved in immune function. Importantly, recent reports have shown that SC2 encodes its own svRNAs. In this study, we have identified 12 svRNAs expressed during SC2 infection and show that one of these svRNAs can regulate target gene expression via complementary binding to mRNA 3' untranslated regions (3'UTRs) much like human microRNAs.

Inability to Access Needed Medical Care Among Asian American, Native Hawaiian, and Pacific Islander Medicaid Enrollees.

We examined self-reported inability to access to needed medical care and reasons for not accessing medical care among US-representative adult Medicaid enrollees, disaggregated across 10 Asian American, Native Hawaiian, and Pacific Islander ethnic groups. Chinese (-4.54 percentage points [PP], P < .001), Other Asian (-4.42 PP, P < .001), and Native Hawaiian (-4.36 PP, P < .001) enrollees were significantly less likely to report being unable to access needed medical care compared with non-Hispanic White enrollees. The most common reason reported was that a health plan would not approve, cover, or pay for care. Mitigating inequities may require different interventions specific to certain ethnic groups.

Arrestin-3 binds parkin and enhances parkin-dependent mitophagy.

Arrestins were discovered for their role in homologous desensitization of G-protein-coupled receptors (GPCRs). Later non-visual arrestins were shown to regulate several signaling pathways. Some of these pathways require arrestin binding to GPCRs, the regulation of others is receptor independent. Here, we demonstrate that arrestin-3 binds the E3 ubiquitin ligase parkin via multiple sites, preferentially interacting with its RING0 domain. Identification of the parkin domains involved suggests that arrestin-3 likely relieves parkin autoinhibition and/or stabilizes the enzymatically active "open" conformation of parkin. Arrestin-3 binding enhances ubiquitination by parkin of the mitochondrial protein mitofusin-1 and facilitates parkin-mediated mitophagy in HeLa cells. Furthermore, arrestin-3 and its mutant with enhanced parkin binding rescue mitofusin-1 ubiquitination and mitophagy in the presence of the Parkinson's disease-associated R275W parkin mutant, which is defective in both functions. Thus, modulation of parkin activity via arrestin-3 might be a novel strategy of anti-parkinsonian therapy.

Causal Factors for Osteoarthritis: A Scoping Review of Mendelian Randomization Studies.

OBJECTIVE: Mendelian randomization (MR) has increasingly been utilized as a tool for establishing causal relations between modifiable exposures and osteoarthritis (OA). The goal of this review was to summarize available MR studies of OA that evaluate the causal role of modifiable risk factors on OA. METHODS: This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Extension for Scoping Reviews model. We performed a literature search for relevant studies published before December 2021 across multiple databases using the search terms "osteoarthritis" and ("Mendelian randomization" or "polygenic risk score"). We reported the MR estimates of causal associations between exposures and OA and then assessed methodologic quality of abstracted studies according to their efforts to validate the three key MR assumptions. RESULTS: Our search identified 45 studies reporting on 141 exposure-association analyses. All studies performed a formal instrumental variable analysis to estimate the causal effect of exposure on OA. Causal associations (P < 0.05) were reported in 60 of these analyses representing 36 unique publications, and MR-Egger sensitivity analyses were performed in 45 of these analyses. MR studies provided support for causal associations of OA with increased levels of adiposity, coffee consumption, bone mineral density, and sleep disturbance, and decreased levels of serum calcium and low-density lipoprotein cholesterol. CONCLUSION: These results highlight the potential benefits of weight reduction and improvement of sleep quality to reduce the risk of OA and call for a better understanding of the relations of coffee consumption and serum calcium to OA risk.

Use of and barriers to adopting standardized social risk screening tools in federally qualified health centers during the first year of the COVID-19 pandemic.

OBJECTIVE: To describe the national rate of social risk factor screening adoption among federally qualified health centers (FQHCs), examine organizational factors associated with social risk screening adoption, and identify barriers to utilizing a standardized screening tool in 2020. DATA SOURCE: 2020 Uniform Data System, a 100% sample of all US FQHCs (N = 1375). STUDY DESIGN: We used multivariable linear probability models to assess the association between social risk screening adoption and key FQHC characteristics. We used descriptive statistics to describe variations in screening tool types and barriers to utilizing standardized tools. We thematically categorized open-ended responses about tools and barriers. DATA COLLECTION: None. PRINCIPAL FINDINGS: In 2020, 68.9% of FQHCs screened patients for any social risk factors. Characteristics associated with a greater likelihood of screening adoption included having high proportions of patients best served in a language other than English (18.8 percentage point [PP] increase, 95% CI: 6.0, 31.6) and being larger in size (10.3 PP increase, 95% CI: 0.7, 20.0). Having higher proportions of uninsured patients (14.2 PP decrease, 95% CI: -25.5, -0.3) and participating in Medicaid-managed care contracts (7.3 PP decrease, 95% CI: -14.2, -0.3) were associated with lower screening likelihood. Among screening FQHCs, the Protocol for Responding to and Assessing Patients' Assets, Risks, and Experiences (PRAPARE) was the most common tool (47.1%). Among non-screening FQHCs, common barriers to using a standardized tool included lack of staff training to discuss social issues (25.2%), inability to include screening in patient intake (21.7%), and lack of funding for addressing social needs (19.2%). CONCLUSIONS: Though most FQHCs screened for social risk factors in 2020, various barriers have prevented nearly 1 in 3 FQHCs from adopting a screening tool. Policies that provide FQHCs with resources to support training and workflow changes may increase screening uptake and facilitate engagement with other sectors.

Health Insurance Coverage and Access to Care by Sexual Orientation During the COVID-19 Pandemic: United States, January 2021-February 2022.

Objectives. To compare health insurance coverage and access to care by sex and sexual minority status during the COVID-19 pandemic and assess whether lack of insurance hindered access to care by sexual minority status. Methods. Using Behavioral Risk Factor Surveillance System data (January 2021-February 2022), we examined differences by sex and sexual orientation among 158 722 adults aged 18 to 64 years living in 34 states. Outcomes were health insurance coverage type and 3 access to care measures. Results. Sexual minority women were significantly more likely to be uninsured than were heterosexual women, and lack of insurance widened the magnitude of disparity by sexual minority status in all measures of access. Compared with heterosexual men with health insurance, sexual minority men with health insurance were significantly more likely to report being unable to afford necessary care. Conclusions. During the pandemic, 1 in 8 sexual minority adults living in 34 study states were uninsured. Among sexual minority women, lack of insurance widened inequities in access to care. There were inequities among sexual minority men with health insurance. Public Health Implications. Sexual minority adults may be disproportionately affected by the unwinding of the COVID-19 public health emergency and may require tailored efforts to mitigate insurance coverage loss. (Am J Public Health. 2024;114(1):118-128. https://doi.org/10.2105/AJPH.2023.307446).

CRISPR/Cas9 mutagenesis of the Arabidopsis GROWTH-REGULATING FACTOR (GRF) gene family.

Genome editing in plants typically relies on T-DNA plasmids that are mobilized by Agrobacterium-mediated transformation to deliver the CRISPR/Cas machinery. Here, we introduce a series of CRISPR/Cas9 T-DNA vectors for minimal settings, such as teaching labs. Gene-specific targeting sequences can be inserted as annealed short oligonucleotides in a single straightforward cloning step. Fluorescent markers expressed in mature seeds enable reliable selection of transgenic or transgene-free individuals using a combination of inexpensive LED lamps and colored-glass alternative filters. Testing these tools on the Arabidopsis GROWTH-REGULATING FACTOR (GRF) genes, we were able to create a collection of predicted null mutations in all nine family members with little effort. We then explored the effects of simultaneously targeting two, four and eight GRF genes on the rate of induced mutations at each target locus. In our hands, multiplexing was associated with pronounced disparities: while mutation rates at some loci remained consistently high, mutation rates at other loci dropped dramatically with increasing number of single guide RNA species, thereby preventing a systematic mutagenesis of the family.

Human YRNA 4 (HY4) plasma levels are a prognostic indicator of SARS-CoV-2 infection clinical severity.

SARS-CoV-2 infection can result in a range of outcomes from asymptomatic/mild disease to severe COVID-19/fatality. In this study, we investigated the differential expression of small noncoding RNAs (sncRNAs) between patient cohorts defined by disease severity. We collected plasma samples, stratified these based on clinical outcomes, and sequenced their circulating sncRNAs. Excitingly, we found YRNA HY4 displays significant differential expression (p=0.025) between patients experiencing mild and severe disease. In agreement with recent reports identifying plasma YRNAs as indicators of influenza infection severity, our results strongly suggest that circulating HY4 levels represent a powerful prognostic indicator of likely SARS-CoV-2 patient infection outcome.

Analytical assay validation for acute myeloid leukemia measurable residual disease assessment by multiparametric flow cytometry.

BACKGROUND: Measurable residual disease (MRD) assessed by multiparametric flow cytometry (MFC) has gained importance in clinical decision-making for acute myeloid leukemia (AML) patients. However, complying with the recent In Vitro Diagnostic Regulations (IVDR) in Europe and Food and Drug Administration (FDA) guidance in the United States requires rigorous validation prior to their use in investigational clinical trials and diagnostics. Validating AML MRD-MFC assays poses challenges due to the unique underlying disease biology and paucity of patient specimens. In this study, we describe an experimental framework for validation that meets regulatory expectations. METHODS: Our validation efforts focused on evaluating assay accuracy, analytical specificity, analytical and functional sensitivity (limit of blank (LoB), detection (LLoD) and quantitation (LLoQ)), precision, linearity, sample/reagent stability and establishing the assay background frequencies. RESULTS: Correlation between different MFC methods was highly significant (r = 0.99 for %blasts and r = 0.93 for %LAIPs). The analysis of LAIP specificity accurately discriminated from negative control cells. The assay demonstrated a LoB of 0.03, LLoD of 0.04, and LLoQ of 0.1%. Precision experiments yielded highly reproducible results (Coefficient of Variation <20%). Stability experiments demonstrated reliable measurement of samples up to 96 h from collection. Furthermore, the reference range of LAIP frequencies in non-AML patients was below 0.1%, ranging from 0.0% to 0.04%. CONCLUSION: In this manuscript, we present the validation of an AML MFC-MRD assay using BM/PB patient specimens, adhering to best practices. Our approach is expected to assist other laboratories in expediting their validation activities to fulfill recent health authority guidelines.

Exposure notification system activity as a leading indicator for SARS-COV-2 caseload forecasting.

PURPOSE: Digital methods to augment traditional contact tracing approaches were developed and deployed globally during the COVID-19 pandemic. These "Exposure Notification (EN)" systems present new opportunities to support public health interventions. To date, there have been attempts to model the impact of such systems, yet no reports have explored the value of real-time system data for predictive epidemiological modeling. METHODS: We investigated the potential to short-term forecast COVID-19 caseloads using data from California's implementation of the Google Apple Exposure Notification (GAEN) platform, branded as CA Notify. CA Notify is a digital public health intervention leveraging resident's smartphones for anonymous EN. We extended a published statistical model that uses prior case counts to investigate the possibility of predicting short-term future case counts and then added EN activity to test for improved forecast performance. Additional predictive value was assessed by comparing the pandemic forecasting models with and without EN activity to the actual reported caseloads from 1-7 days in the future. RESULTS: Observation of time series presents noticeable evidence for temporal association of system activity and caseloads. Incorporating earlier ENs in our model improved prediction of the caseload counts. Using Bayesian inference, we found nonzero influence of EN terms with probability one. Furthermore, we found a reduction in both the mean absolute percentage error and the mean squared prediction error, the latter of at least 5% and up to 32% when using ENs over the model without. CONCLUSIONS: This preliminary investigation suggests smartphone based ENs can significantly improve the accuracy of short-term forecasting. These predictive models can be readily deployed as local early warning systems to triage resources and interventions.

Continuous Subcutaneous Infusion Versus Multiple Daily Injections of Insulin for Pregestational Diabetes in Pregnancy: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of continuous subcutaneous insulin infusion (CSII) therapy in pregnancies affected by pregestational diabetes mellitus (DM) has generated mixed outcome data worthy of further investigation. This systematic review and meta-analysis aims to evaluate clinical outcomes associated with CSII versus multiple daily injections (MDIs) in pregnant persons with pregestational DM. METHODS: A predefined, systematic, librarian-assisted search of MEDLINE (PubMed), Embase, Cochrane Library, Scopus, ClinicalTrials.gov, and World Health Organization International Clinical Trial Registry Platform (published from 2010 to 2022) yielded 3003 studies describing pregnancy outcomes associated with CSII and/or MDI for pregestational DM. The primary exposure was mode of insulin administration, with cesarean delivery and neonatal hypoglycemia as the primary maternal and neonatal outcomes, respectively. Secondary outcomes included hypertensive disorders of pregnancy, first and third-trimester glycemic control, large-for-gestational age (LGA) neonate, preterm birth, neonatal intensive care unit admission, need for respiratory support, hyperbilirubinemia, 5-minute Apgar <7, shoulder dystocia, and perinatal mortality. We calculated pooled odds ratios (OR) with 95% confidence intervals (CI) using random-effects models. RESULTS: Among 39 eligible studies, 39% of the 5518 pregnancies included were exposed to CSII. Odds of cesarean delivery were higher with CSII (20 studies: 63% vs 56%, odds ratio [OR] 1.3 [95% confidence interval (CI) 1.2-1.5]), but we did not identify a difference in the odds of neonatal hypoglycemia (23 studies: 31% vs 34%, OR 1.1 [95% CI 0.9-1.5]). Among secondary outcomes, only the odds of LGA (20 studies: 47% vs 38%, OR 1.4 [95% CI 1.2-1.6]) were higher in individuals using CSII versus MDI. CONCLUSIONS: Use of CSII (vs MDI) for pregestational DM in pregnancy is associated with higher odds of cesarean delivery and delivery of an LGA neonate. Further evaluation of how CSII use may influence neonatal size and delivery route is warranted.

Characteristics and genomic epidemiology of colistin-resistant Enterobacterales from farmers, swine, and hospitalized patients in Thailand, 2014-2017.

BACKGROUND: Colistin is one of the last resort therapeutic options for treating carbapenemase-producing Enterobacterales, which are resistant to a broad range of beta-lactam antibiotics. However, the increased use of colistin in clinical and livestock farming settings in Thailand and China, has led to the inevitable emergence of colistin resistance. To better understand the rise of colistin-resistant strains in each of these settings, we characterized colistin-resistant Enterobacterales isolated from farmers, swine, and hospitalized patients in Thailand. METHODS: Enterobacterales were isolated from 149 stool samples or rectal swabs collected from farmers, pigs, and hospitalized patients in Thailand between November 2014-December 2017. Confirmed colistin-resistant isolates were sequenced. Genomic analyses included species identification, multilocus sequence typing, and detection of antimicrobial resistance determinants and plasmids. RESULTS: The overall colistin-resistant Enterobacterales colonization rate was 26.2% (n = 39/149). The plasmid-mediated colistin-resistance gene (mcr) was detected in all 25 Escherichia coli isolates and 9 of 14 (64.3%) Klebsiella spp. isolates. Five novel mcr allelic variants were also identified: mcr-2.3, mcr-3.21, mcr-3.22, mcr-3.23, and mcr-3.24, that were only detected in E. coli and Klebsiella spp. isolates from farmed pigs. CONCLUSION: Our data confirmed the presence of colistin-resistance genes in combination with extended spectrum beta-lactamase genes in bacterial isolates from farmers, swine, and patients in Thailand. Differences between the colistin-resistance mechanisms of Escherichia coli and Klebsiella pneumoniae in hospitalized patients were observed, as expected. Additionally, we identified mobile colistin-resistance mcr-1.1 genes from swine and patient isolates belonging to plasmids of the same incompatibility group. This supported the possibility that horizontal transmission of bacterial strains or plasmid-mediated colistin-resistance genes occurs between humans and swine.

Modulation of type I interferon responses potently inhibits SARS-CoV-2 replication and inflammation in rhesus macaques.

Type I interferons (IFN-I) are critical mediators of innate control of viral infections but also drive the recruitment of inflammatory cells to sites of infection, a key feature of severe coronavirus disease 2019. Here, IFN-I signaling was modulated in rhesus macaques (RMs) before and during acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection using a mutated IFN-α2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous IFN-I. IFNmod treatment in uninfected RMs was observed to induce a modest up-regulation of only antiviral IFN-stimulated genes (ISGs); however, in SARS-CoV-2-infected RMs, IFNmod reduced both antiviral and inflammatory ISGs. IFNmod treatment resulted in a potent reduction in SARS-CoV-2 viral loads both in vitro in Calu-3 cells and in vivo in bronchoalveolar lavage (BAL), upper airways, lung, and hilar lymph nodes of RMs. Furthermore, in SARS-CoV-2-infected RMs, IFNmod treatment potently reduced inflammatory cytokines, chemokines, and CD163+ MRC1- inflammatory macrophages in BAL and expression of Siglec-1 on circulating monocytes. In the lung, IFNmod also reduced pathogenesis and attenuated pathways of inflammasome activation and stress response during acute SARS-CoV-2 infection. Using an intervention targeting both IFN-α and IFN-ß pathways, this study shows that, whereas early IFN-I restrains SARS-CoV-2 replication, uncontrolled IFN-I signaling critically contributes to SARS-CoV-2 inflammation and pathogenesis in the moderate disease model of RMs.

Diabetes Research and Resource Sharing During the COVID-19 Pandemic: A Systematic Review and Experience from an Academic/Non-Profit Resource Website.

BACKGROUND: The magnitude of the response of the diabetes professional community to the COVID-19 pandemic is not known. We aimed to examine diabetes technology research trends and resources offered by professional organizations during this period. METHODS: We explored patterns of the response from the professional diabetes community to the pandemic by (1) systematically searching for articles related to diabetes, COVID-19, and diabetes technologies; (2) examining publication trends of research protocols (clinicaltrials.gov) and preprints (medRxiv); and (3) reviewing online resources from professional organizations including our website (COVIDinDiabetes.org; an Emory University-Diabetes Technology Society collaboration). RESULTS: We identified 492 articles published between December 2019 and December 2022 meeting our inclusion criteria. Telemedicine and continuous glucose monitoring were the most common reported technologies from most parts of the world. The largest number of preprint articles was published in 2020, with a decline in 2021 and 2022. The number of research protocols related to COVID-19 was the highest in 2020 and declined in 2021 and 2022. Resources from organizations included protocols adapted to treat patients with diabetes and COVID-19, training programs, emergency preparedness, and literature on diabetes and COVID-19. On our website (COVIDinDiabetes.org), there were 12 236 visits and 18 149 pageviews, with 1.6 actions per visits, with most visits coming from North America (N = 7233, 54.2%), South America (N = 2663, 21.8%), and Europe (N = 1219). CONCLUSIONS: We conclude that the COVID-19 pandemic promoted unprecedented global research productivity related to diabetes and COVID-19 and that the transition to the use of technology resources has been evident during this period.