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Abstract Background Patients have typically received health care through face-to-face encounters. However, expansion of electronic communication and electronic health records (EHRs) provide alternative means for patient and physicians to interact. Electronic consultations may complement regular healthcare by providing “better, faster, cheaper” processes for diagnosing, treating, and monitoring health conditions. Virtual consultation between physicians may provide a method of streamlining care, potentially saving patients the time and expense of added visits. The purpose of this study was to compare physician usage and patient satisfaction with virtual consultations (VCs) with traditional consultations (TCs) facilitated within an EHR. Methods We conducted an observational case–control survey study within Kaiser Permanente, Colorado. A sample of patients who had VCs requested by physicians (N = 270) were matched with patients who had TCs requested by physicians (N = 270), by patient age, gender, reason for the consult, and specialty department. These patients (VC and TC), were invited to participate in a satisfaction survey. In addition, 205 primary care physicians who submitted a VC or TC were surveyed. Results During the study period, 58,146 VC or TC were requested (TC = 96.3%). Patients who completed a satisfaction survey (267 out of 540 patients, 49.4% response rate) indicated they were satisfied with their care, irrespective of the kind of consult (mean 10-point Likert score of 8.5). 88 of 205 primary care physicians surveyed (42.9%) returned at least one survey; VC and TC survey response rates and consulted departments were comparable (p = 0.13). More TCs than VCs requested transfer of patient care (p = 0.03), assistance with diagnosis (p = 0.04) or initiating treatment (p =0.04). Within 3 weeks of the consultation request, 72.1% of respondents reported receiving information from VCs, compared with 33.9% of the TCs (p < 0.001). Utility of information provided by consultants and satisfaction with consultations did not differ between VCs and TCs. Conclusions Referring physicians received information from consultants more quickly from VCs compared with TCs, but the value and application of information from both types of consultations were similar. VCs may decrease the need for face-to-face specialty encounters without a decrease in the patient’s perception of care.

We report a mechanism that underlies stress-induced cognitive inflexibility at the molecular level. In a mouse model under subacute cellular stress in which deficits in rule shifting tasks were elicited, the nuclear glyceraldehyde dehydrogenase (N-GAPDH) cascade was activated specifically in microglia in the prelimbic cortex. The cognitive deficits were normalized with a pharmacological intervention with a compound (the RR compound) that selectively blocked the initiation of N-GAPDH cascade without affecting glycolytic activity. The normalization was also observed with a microglia-specific genetic intervention targeting the N-GAPDH cascade. At the mechanistic levels, the microglial secretion of High-Mobility Group Box (HMGB), which is known to bind with and regulate the NMDA-type glutamate receptors, was elevated. Consequently, the hyperactivation of the prelimbic layer 5 excitatory neurons, a neural substrate for cognitive inflexibility, was also observed. The upregulation of the microglial HMGB signaling and neuronal hyperactivation were normalized by the pharmacological and microglia-specific genetic interventions. Taken together, we show a pivotal role of cortical microglia and microglia-neuron interaction in stress-induced cognitive inflexibility. We underscore the N-GAPDH cascade in microglia, which causally mediates stress-induced cognitive alteration., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Use principles of implementation science to improve the diagnosis and management of potentially significant imaging findings., Methods: Multidisciplinary stakeholders codified the diagnosis and management of potentially significant imaging findings in eight organs and created a finding tracking management system that was embedded in radiologist workflows and IT systems. Radiologists were trained to use this system. An automated finding tracking management system was created to support consistent high-quality care through care pathway visualizations, increased awareness of specific findings in the electronic medical record, templated notifications, and creation of an electronic safety net. Primary outcome was the rate of quality reviews related to eight targeted imaging findings. Secondary outcome was radiologist use of the finding tracking management tool., Results: In the 4 years after implementation, the tool was used to track findings in 7,843 patients who received 10,015 ultrasound, CT, MRI, x-ray, and nuclear medicine examinations that were interpreted by all 34 radiologists. Use of the tool lead to a decrease in related quality reviews (from 8.0% to 0.0%, P < .007). Use of the system increased from 1.7% of examinations in the early implementation phase to 3.1% (+82%, P < .00001) in the postimplementation phase. Each radiologist used the tool on an average of 294.6 unique examinations (SD 404.8). Overall, radiologists currently use the tool approximately 4,000 times per year., Discussion: Radiologists frequently used a finding tracking management system to ensure effective communication and raise awareness of the importance of recommended future follow-up studies. Use of this system was associated with a decrease in the rate of quality review requests in this domain., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Mobile health applications are increasingly used to support the delivery of health care services to a variety of patients. Based on data obtained from a pragmatic trial of the electronic Patient Reported Outcome (ePRO) app designed to support goal-oriented care primary care, this study aims to (1) examine how patient-reported usability changed over the one-year intervention period, and (2) explore participant attrition rate of the electronic Patient Reported Outcome app over one year study period., Methods: We performed a secondary analysis of 44 older adults with complex chronic needs enrolled in the electronic Patient Reported Outcome-digital health intervention. App usage and attrition were measured using device-generated usage logs; usability was measured using the patient-reported post-study system usability questionnaire collected at 3, 6, 9, and 12 months. Research memos were used to interpret potential contextual contributing factors to patients' overall usage and usability score pattern. A data triangulation method of both quantitative and qualitative data was used to analyze and interpret study findings., Results: While there was gradual attrition in the use of the ePRO app, patients' usability scores remained consistent throughout the study period. Qualitative memos suggested patients' encounters with technical difficulties and relationship dynamics with primary providers influenced patients' adherence to the ePRO app., Conclusion: This study highlights that the patient-provider relationship is a key determining factor that influences complex patients' continued engagement with a Mobile health app. The finding calls attention to the measurement of usability of a Mobile health app, its impact on attrition, and contributing factors that influence patients' attrition. Trial registration: Clinicaltrials.gov Identified NCT02917954., (© The Author(s) 2021.)

Objective: To estimate the incidence of occult uterine sarcoma and leiomyosarcoma in hysterectomies for leiomyomas and the risk associated with their morcellation., Methods: We conducted a population-based cohort study. All uterine sarcomas from 2006-2013 in an integrated health care system were identified. Age- and race-specific incidences of occult uterine sarcoma were calculated. Kaplan-Meier survival analysis was performed. Crude and adjusted risk ratios of recurrence and death associated with morcellation at 1, 2, and 3 years were estimated using Poisson regression with inverse probability weighting., Results: There were 125 hysterectomies with occult uterine sarcomas identified among 34,728 hysterectomies performed for leiomyomas. The incidence of occult uterine sarcoma and leiomyosarcoma was 1 of 278 or 3.60 (95% confidence interval [CI] 2.97-4.23) and 1 of 429 or 2.33 (95% CI 1.83-2.84) per 1,000 hysterectomies. For stage I leiomyosarcoma (n=111), eight (7.2%) were power and 27 (24.3%) nonpower-morcellated. The unadjusted 3-year probability of disease-free survival for no morcellation, power and nonpower morcellation was 0.54, 0.19, and 0.51, respectively (P=.15); overall survival was 0.64, 0.75, and 0.68, respectively (P=.97). None of the adjusted risk ratios for recurrence or death were significant except for death at 1 year for power and nonpower morcellation groups combined (6/33) compared with no morcellation (4/76) (5.12, 95% CI 1.33-19.76, P=.02). We had inadequate power to infer differences for all other comparisons including 3-year survival and power morcellation., Conclusion: Morcellation is associated with decreased early survival of women with occult leiomyosarcomas. We could not accurately assess associations between power morcellation and 3-year survival as a result of small numbers.

Information technology (IT) in healthcare, also referred to as eHealth technologies, may offer a promising solution to the provision of better care and support for people who have multiple conditions and complex care needs, and their caregivers. eHealth technologies can include electronic medical records, telemonitoring systems and web-based portals, and mobile health (mHealth) technologies that enable information sharing between providers, patients, clients and their families. IT often acts as an enabler of improved care delivery, rather than being an intervention per se. But how are different countries seeking to leverage adoption of these technologies to support people who have chronic conditions and complex care needs? This article presents three case examples from Ontario (Canada), Scotland and Kaiser Permanente Colorado (United States) to identify how these jurisdictions are currently using technology to address multimorbidity. A SWOT (strengths, weaknesses, opportunities, threats) analysis is presented for each case and a final discussion addresses the future of eHealth for complex care needs. The case reports presented in this manuscript mark the foundational work of the Multi-National eHealth Research Partnership Supporting Complex Chronic Disease and Disability (the eCCDD Network); a CIHR-funded project intended to support the international development and uptake of eHealth tools for people with complex care needs.

Medical countermeasures (MCMs) are medical products used during public health emergencies. This study, conducted within the Mini-Sentinel Initiative, sought to develop the patient identification and matching processes necessary to assess safety outcomes for MCMs. A handheld device was used to collect identifying information (e.g., name, birthdate, and sex) from the driver's licenses of 421 individuals presenting for routine care at their primary care medical office. Overall, 374 individuals (88.8%) could be linked to their electronic health data using driver's license information. The device was also pilot-tested at a seasonal influenza immunization clinic: detailed vaccine information (e.g., lot number and manufacturer) was captured with a high degree of accuracy. This investigation demonstrated that a handheld device is a feasible means of collecting patient identity and medical product receipt data. This capacity should be useful for safety surveillance of MCMs, particularly when dispensed in settings outside the traditional health-care delivery system.

Introduction: Syndromic surveillance systems can be useful in detecting naturally occurring illness., Objectives: Syndromic surveillance performance was assessed to identify an early and severe influenza A outbreak in Denver in 2003., Methods: During October 1, 2003-January 31, 2004, syndromic surveillance signals generated for detecting clusters of influenza-like illness (ILI) were compared with ILI activity identified through a sentinel provider system and with reports of laboratory-confirmed influenza. The syndromic surveillance and sentinel provider systems identified ILI activity based on ambulatory-care visits to Kaiser Permanente Colorado. The syndromic surveillance system counted a visit as ILI if the provider recorded any in a list of 30 respiratory diagnoses plus fever. The sentinel provider system required the provider to select "influenza" or "ILI.", Results: Laboratory-confirmed influenza cases, syndromic surveillance ILI episodes, and sentinel provider reports of patient visits for ILI all increased substantially during the week ending November 8, 2003. A greater absolute increase in syndromic surveillance episodes was observed than in sentinel provider reports, suggesting that sentinel clinicians failed to code certain cases of influenza. During the week ending December 6, when reports of laboratory-confirmed cases peaked, the number of sentinel provider reports exceeded the number of syndromic surveillance episodes, possibly because clinicians diagnosed influenza without documenting fever., Conclusion: Syndromic surveillance performed as well as the sentinel provider system, particularly when clinicians were advised to be alert to influenza, suggesting that syndromic surveillance can be useful for detecting clusters of respiratory illness in various settings.

Intestinal reactive hyperemia is an abrupt blood flow increase following release from anterior mesenteric arterial occlusion. We investigated the role of adenosine in reactive hyperemia. In anesthetized rats, mesenteric arterial velocity of blood flow was determined with pulsed Doppler velocimetry and arterial pressure with a transducer. Three indices quantifying reactive hyperemias obtained following 30, 60, and 120 s arterial occlusions included duration, the volume of blood flow exceeding preocclusion blood flow, and the percentage increase in conductance. In six rat groups (half fasted and half with intrajejunal bile-oleate solutions), hyperemia parameters were determined before and after administration of either adenosine deaminase (ADA) or two adenosine receptor antagonists, namely 8-phenyltheophylline (8-PT) and 1,3-dipropyl-7-methylxanthine (DPMX). In fasted gut the three agents had variable effectiveness against reactive hyperemia, although 8-PT was the most consistent inhibitor. Instillation of intrajejunal lipid evoked a stable hyperemia and increased duration and blood flow volume after each occlusive period. ADA and 8-PT were more effective against reactive hyperemia in fed gut than in fasted gut. Our findings suggest that adenosine is a vasodilator metabolite modulating mesenteric reactive hyperemia, especially during enhanced intestinal metabolic activity.

This study was designed to evaluate the role of adenosine and adenosine receptors in the reactive (RH) and functional hyperemia (FH) in rat gut. Experiments were performed on anesthetized rats. Mesenteric blood flow was measured with a pulsed Doppler flowmeter. We also determined the duration of reactive hyperemia, excess volume of blood flow above control value and maximal increase in mesenteric vascular conductance during both hyperemic responses. Data were collected following release from occlusions lasting 30, 60 and 120 sec. Functional hyperemia was induced by perfusion of the gut with a solution. Studied parameters were obtain before and after adenosine deaminase (ADA) and two adenosine receptor antagonists: 8-phenyltheophylline (8-PT) and 1.3-dipropyl-7-methyl-xanthine (DPMX). In fasted rats ADA and 8-PT reduced of RH after each period of occlusion and DPMX was ineffective in reducing any parameter of RH. In fed rats control mesenteric blood flow was increased. ADA, 8-PT, and DPMX were more effective inhibitors of RH and FH. Above findings suggest that adenosine play a role in the modulation of RH and FH acting on A2 subtype receptors.

The chromatin structure of the palindromic macronuclear ribosomal RNA genes of Tetrahymena thermophila was probed with micrococcal nuclease. Independent of the state of transcriptional activity, the transcribed region had a shorter nucleosome repeat (184 +/- 3 base pairs) than the non-transcribed central spacer or bulk chromatin (both 200 base pairs). The transcribed region displayed an increased sensitivity to micrococcal nuclease in rapidly growing cells, which suggested an altered chromatin structure during transcription. At early stages of nuclease digestion, the central spacer appeared to be in a highly structured nucleosomal array. Based on the differences in nucleosome repeat distance and sensitivity to nuclease, we conclude that quite different chromatin structures are maintained in two adjacent regions of the Tetrahymena ribosomal RNA gene. The DNA of the non-transcribed terminal spacer was found to contain sequences which are highly susceptible to micrococcal nuclease, precluding any conclusions about nucleosome structure in this region.

DNA renaturation kinetics was used to examine the relative accessibility of various regions of the Tetrahymena ribosomal RNA gene (rDNA) chromatin to micrococcal nuclease. In nuclei from cells active in rRNA transcription, the transcribed region of the rDNA chromatin was as much as 5-fold more accessible than the average of the total chromatin. As few as 20% inactive genes in the population could have accounted for all of the hybridization, so the transcribed region of the active units may be totally unprotected from nuclease degradation. The terminal non-transcribed spacer downstream from the transcription unit was also preferentially digested, but to a smaller degree. The central non-transcribed spacer was degraded to the same extent as total chromatin after a high degree of nuclease digestion. In nuclei from starved cells, which have 96% reduced rRNA transcription, the transcribed and terminal spacer regions of the rDNA were again more accessible than the total chromatin from the same nuclei, but the difference did not exceed 2-fold. We conclude that transcriptional activation is accompanied by major changes in the structure of the ribosomal gene chromatin, and that the extent and/or type of structural alteration differs in each functionally defined region of the rDNA.

A new membrane bound protease has been identified in bovine hypothalamic neurosecretory granules using synthetic substrates that we prepared based on the sequence in pro-gonadotropin-releasing hormone protein that overlaps gonadotropin-releasing hormone and gonadotropin-associated peptide (thought to be prolactin-releasing hormone-inhibiting hormone). The enzyme was solubilized from neurosecretory granules using the detergent Triton X-100 and was further purified by high-performance gel permeation liquid chromatography. The enzyme hydrolyzes the Arg-2-naphthylamide (NA) bond of benzoyl(Bz)-Gly-Leu-Arg-Pro-Gly-Gly-Lys-Arg-2-NA which contains two likely processing sites, Arg-Pro and Lys-Arg. On the basis of the ratio of Vmax to Km as a measure of substrate specificity, Bz-Gly-Leu-Arg-Pro-Gly-Gly-Lys-Arg-2-NA is about 50-fold better than Bz-Gly-Gly-Lys-Arg-2-NA. Bz-Leu-Arg-2-NA and Bz-Gly-Leu-Arg-Pro-Gly-Gly are not hydrolyzed. The pH optimum for hydrolysis is 7.2 (Bz-Gly-Gly-Lys-Arg-2-NA substrate). As determined by gel permeation chromatography, the apparent molecular weight of the enzyme depends on the chromatography conditions; in the absence of NaCl, the Mr is approximately equal to 160,000 but is approximately equal to 80,000 if NaCl is included in the eluting buffer. After high-performance gel permeation liquid chromatography, the peak fraction containing the enzyme was lyophilized and then subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis; silver staining revealed a single protein band, Mr approximately equal to 70,000.

We examined the specificity of a bovine hypothalamic neurosecretory granule enzyme which we discovered and which is capable of processing pro-gonadotropin releasing hormone precursor protein to yield gonadotropin associated peptide and a C-terminal extended form of gonadotropin releasing hormone (Palen et al.). The sequence in the precursor protein that separates the two active peptides is -Gly-Gly-Lys-Arg- where the pair of basic residues, -Lys-Arg-, is the anticipated cleavage site. On the basis of Vmax/Km as the measure of substrate specificity, Benzoyl(Bz)-Gly-Gly-Lys-Arg-2-Napthylamide (NA) greater than Bz-Gly-Gly-Arg-Lys-2-NA much greater than Bz-Gly-Gly-Arg-Arg-2-NA approximately equal to Bz-Gly-Gly-Lys-Lys-2-NA. Bz-Gly-Gly-Lys(N(epsilon)-acetyl)-Arg-2-NA is a very poor substrate. Our results indicate that the composition and sequence of the pair of basic residues at the primary cleavage site is important for enzyme specificity and that changes in the P1 or P2 residues of a potential substrate may affect both Km and Vmax. Hydrolysis of all substrates occurs at the P1-2-NA bond. We had previously shown that there is no cleavage between the pair of basic residues. With longer peptide substrates, Bz-Gly-Leu-Arg-Pro-Gly-Gly-Lys-Arg-2-NA greater than Bz-Gly-Leu-Arg(NO2)-Pro-Gly-Gly-Lys-Arg-2-NA greater than Bz-Gly-Gly-Lys-Arg-2-NA. Extending the substrate sequence to more closely resemble the amino acid sequence in the precursor protein improves Km 10-fold and Vmax about 5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)