The Potential of Evidence-Based Clinical Intake Tools to Discover or Ground Prevalence of Symptoms Using Real-Life Digital Health Encounters: Retrospective Cohort Study.

BACKGROUND: Evidence-based clinical intake tools (EBCITs) are structured assessment tools used to gather information about patients and help health care providers make informed decisions. The growing demand for personalized medicine, along with the big data revolution, has rendered EBCITs a promising solution. EBCITs have the potential to provide comprehensive and individualized assessments of symptoms, enabling accurate diagnosis, while contributing to the grounding of medical care. OBJECTIVE: This work aims to examine whether EBCITs cover data concerning disorders and symptoms to a similar extent as physicians, and thus can reliably address medical conditions in clinical settings. We also explore the potential of EBCITs to discover and ground the real prevalence of symptoms in different disorders thereby expanding medical knowledge and further supporting medical diagnoses made by physicians. METHODS: Between August 1, 2022, and January 15, 2023, patients who used the services of a digital health care (DH) provider in the United States were first assessed by the Kahun EBCIT. Kahun platform gathered and analyzed the information from the sessions. This study estimated the prevalence of patients' symptoms in medical disorders using 2 data sets. The first data set analyzed symptom prevalence, as determined by Kahun's knowledge engine. The second data set analyzed symptom prevalence, relying solely on data from the DH patients gathered by Kahun. The variance difference between these 2 prevalence data sets helped us assess Kahun's ability to incorporate new data while integrating existing knowledge. To analyze the comprehensiveness of Kahun's knowledge engine, we compared how well it covers weighted data for the symptoms and disorders found in the 2019 National Ambulatory Medical Care Survey (NMCAS). To assess Kahun's diagnosis accuracy, physicians independently diagnosed 250 of Kahun-DH's sessions. Their diagnoses were compared with Kahun's diagnoses. RESULTS: In this study, 2550 patients used Kahun to complete a full assessment. Kahun proposed 108,523 suggestions related to symptoms during the intake process. At the end of the intake process, 6496 conditions were presented to the caregiver. Kahun covered 94% (526,157,569/562,150,572) of the weighted symptoms and 91% (1,582,637,476/173,4783,244) of the weighted disorders in the 2019 NMCAS. In 90% (224/250) of the sessions, both physicians and Kahun suggested at least one identical disorder, with a 72% (367/507) total accuracy rate. Kahun's engine yielded 519 prevalences while the Kahun-DH cohort yielded 599; 156 prevalences were unique to the latter and 443 prevalences were shared by both data sets. CONCLUSIONS: ECBITs, such as Kahun, encompass extensive amounts of knowledge and could serve as a reliable database for inferring medical insights and diagnoses. Using this credible database, the potential prevalence of symptoms in different disorders was discovered or grounded. This highlights the ability of ECBITs to refine the understanding of relationships between disorders and symptoms, which further supports physicians in medical diagnosis.

Population differences in antibody response to SARS-CoV-2 infection and BNT162b2 vaccination.

The concentration of SARS-CoV-2-specific serum antibodies, elicited by vaccination or infection, is a primary determinant of anti-viral immunity, which correlates with protection against infection and COVID-19. Serum samples were obtained from 25 897 participants and assayed for anti-SARS-CoV-2 spike protein RBD IgG antibodies. The cohort was composed of newly vaccinated BNT162b2 recipients, in the first month or 6 months after vaccination, COVID-19 patients and a general sample of the Israeli population. Antibody levels of BNT162b2 vaccine recipients were negatively correlated with age, with a prominent decrease in recipients over 55 years old, which was most significant in males. This trend was observable within the first month and 6 months after vaccination, while younger participants were more likely to maintain stable levels of serum antibodies. The antibody concentration of participants previously infected with SARS-CoV-2 was lower than the vaccinated and had a more complex, non-linear relation to age, sex and COVID-19 symptoms. Taken together, our data supports age and sex as primary determining factors for both the magnitude and durability of humoral response to SARS-CoV-2 infection and the COVID-19 vaccine. Our results could inform vaccination policies, prioritizing the most susceptible populations for repeated vaccination.

Identifying Profiles of Patients With Uncontrolled Type 2 Diabetes Who Would Benefit From Referral to an Endocrinologist.

OBJECTIVE: To compare the outcomes of glycemic uncontrolled diabetes mellitus type 2 patients receiving treatment from endocrinologists with those treated by primary care physicians. Additionally, this research aims to identify patient profiles that would benefit from personalized referral-a novel medical approach that aims to match the most suitable specialist for effectively managing patient while considering the patient's profile. METHODS: This retrospective cohort study uses the Maccabi Healthcare Services diabetes registry to match 508 pairs of glycemic uncontrolled diabetes mellitus type 2 patients treated by endocrinologists (EndoG) and primary care physicians (PcPG). Using a generalized additive model, we analyzed the hemoglobin A1c (HbA1c) trend over 1 year for each group. We employed the odds ratio (OR) from conditional logistic regression to determine the likelihood of favorable outcomes in the EndoG compared to the PcPG, using the entire cohort and subcohort profiles. RESULTS: The generalized additive model comparison indicated an improvement in HbA1c levels in both groups, with the EndoG outperforming the PcPG. Furthermore, the EndoG group had an OR = 2.27 (95% confidence interval, 1.6 to 3.2) for reducing HbA1c by at least 1% within a year and an OR = 1.68 (95% confidence interval, 1.02 to 2.76) for achieving low-density lipoprotein levels< 100 mg/dl. We identified 96 profiles with positive outcomes, all favoring treatment by endocrinologists. CONCLUSIONS: EndoG demonstrated superior HbA1c control over time and achieved better outcomes compared to PcPG. The identification of 96 profiles benefiting from endocrinologist referral emphasizes the potential of personalized referral.

Hippocampal differential expression underlying the neuroprotective effect of delta-9-tetrahydrocannabinol microdose on old mice.

Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive compound of the cannabis plant and an exogenous ligand of the endocannabinoid system. In previous studies, we demonstrated that a single microdose of THC (0.002 mg/kg, 3-4 orders of magnitude lower than the standard dose for rodents) exerts distinct, long-term neuroprotection in model mice subjected to acute neurological insults. When administered to old, healthy mice, the THC microdose induced remarkable long-lasting (weeks) improvement in a wide range of cognitive functions, including significant morphological and biochemical brain alterations. To elucidate the mechanisms underlying these effects, we analyzed the gene expression of hippocampal samples from the model mice. Samples taken 5 days after THC treatment showed significant differential expression of genes associated with neurogenesis and brain development. In samples taken 5 weeks after treatment, the transcriptional signature was shifted to that of neuronal differentiation and survival. This study demonstrated the use of hippocampal transcriptome profiling in uncovering the molecular basis of the atypical, anti-aging effects of THC microdose treatment in old mice.

Comprehensive Genetic Analysis of Druze Provides Insights into Carrier Screening.

BACKGROUND: Druze individuals, like many genetically homogeneous and isolated populations, harbor recurring pathogenic variants (PV) in autosomal recessive (AR) disorders. METHODS: Variant calling of whole-genome sequencing (WGS) of 40 Druze from the Human Genome Diversity Project (HGDP) was performed (HGDP-cohort). Additionally, we performed whole exome sequencing (WES) of 118 Druze individuals: 38 trios and 2 couples, representing geographically distinct clans (WES-cohort). Rates of validated PV were compared with rates in worldwide and Middle Eastern populations, from the gnomAD and dbSNP datasets. RESULTS: Overall, 34 PVs were identified: 30 PVs in genes underlying AR disorders, 3 additional PVs were associated with autosomal dominant (AD) disorders, and 1 PV with X-linked-dominant inherited disorder in the WES cohort. CONCLUSIONS: The newly identified PVs associated with AR conditions should be considered for incorporation into prenatal-screening options offered to Druze individuals after an extension and validation of the results in a larger study.

Elevated Expression of RGS2 May Underlie Reduced Olfaction in COVID-19 Patients.

Anosmia is common in COVID-19 patients, lasting for weeks or months following recovery. The biological mechanism underlying olfactory deficiency in COVID-19 does not involve direct damage to nasal olfactory neurons, which do not express the proteins required for SARS-CoV-2 infection. A recent study suggested that anosmia results from downregulation of olfactory receptors. We hypothesized that anosmia in COVID-19 may also reflect SARS-CoV-2 infection-driven elevated expression of regulator of G protein signaling 2 (RGS2), a key regulator of odorant receptors, thereby silencing their signaling. To test our hypothesis, we analyzed gene expression of nasopharyngeal swabs from SARS-CoV-2 positive patients and non-infected controls (two published RNA-sequencing datasets, 580 individuals). Our analysis found upregulated RGS2 expression in SARS-CoV-2 positive patients (FC = 14.5, Padj = 1.69 × 10-5 and FC = 2.4; Padj = 0.001, per dataset). Additionally, RGS2 expression was strongly correlated with PTGS2, IL1B, CXCL8, NAMPT and other inflammation markers with substantial upregulation in early infection. These observations suggest that upregulated expression of RGS2 may underlie anosmia in COVID-19 patients. As a regulator of numerous G-protein coupled receptors, RGS2 may drive further neurological symptoms of COVID-19. Studies are required for clarifying the cellular mechanisms by which SARS-CoV-2 infection drives the upregulation of RGS2 and other genes implicated in inflammation. Insights on these pathway(s) may assist in understanding anosmia and additional neurological symptoms reported in COVID-19 patients.