Search

Continuity of care has been an identifying characteristic of family medicine since its inception and is an essential ingredient for high-functioning health care teams. Many benefits, including the quadruple aim of enhancing patient experience, improving population health, reducing costs, and improving care team well-being, are ascribed to continuity of care. In 2023, the Accreditation Council for Graduate Medical Education (ACGME) added two new continuity requirements-annual patient-sided continuity and annual resident-sided continuity-in family medicine training programs. This article reviews continuity of care as it applies to family medicine training programs. We discuss the various types of continuity and issues surrounding the measurement of continuity. A generally agreed upon definition of patient-sided and resident-sided continuity is presented to allow programs to begin to collect the necessary data. Especially within resident training programs, intricacies associated with maintaining continuity of care, such as empanelment, resident turnover, and scheduling, are discussed. The importance of right-sizing resident panels is highlighted, and a mechanism for accomplishing this is presented. The recent ACGME requirements represent a cultural shift from measuring resident experience based on volume to measuring resident continuity. This cultural shift forces family medicine training programs to adapt their various systems, policies, and procedures to emphasize continuity. We hope this manuscript's review of several facets of contuinuity, some unique to training programs, helps programs ensure compliance with the ACGME requirements.

Background: Despite the touted potential of artificial intelligence (AI) and machine learning (ML) to revolutionize health care, clinical decision support tools, herein referred to as medical modeling software (MMS), have yet to realize the anticipated benefits. One proposed obstacle is the acknowledged gaps in AI translation. These gaps stem partly from the fragmentation of processes and resources to support MMS transparent documentation. Consequently, the absence of transparent reporting hinders the provision of evidence to support the implementation of MMS in clinical practice, thereby serving as a substantial barrier to the successful translation of software from research settings to clinical practice., Objective: This study aimed to scope the current landscape of AI- and ML-based MMS documentation practices and elucidate the function of documentation in facilitating the translation of ethical and explainable MMS into clinical workflows., Methods: A scoping review was conducted in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. PubMed was searched using Medical Subject Headings key concepts of AI, ML, ethical considerations, and explainability to identify publications detailing AI- and ML-based MMS documentation, in addition to snowball sampling of selected reference lists. To include the possibility of implicit documentation practices not explicitly labeled as such, we did not use documentation as a key concept but as an inclusion criterion. A 2-stage screening process (title and abstract screening and full-text review) was conducted by 1 author. A data extraction template was used to record publication-related information; barriers to developing ethical and explainable MMS; available standards, regulations, frameworks, or governance strategies related to documentation; and recommendations for documentation for papers that met the inclusion criteria., Results: Of the 115 papers retrieved, 21 (18.3%) papers met the requirements for inclusion. Ethics and explainability were investigated in the context of AI- and ML-based MMS documentation and translation. Data detailing the current state and challenges and recommendations for future studies were synthesized. Notable themes defining the current state and challenges that required thorough review included bias, accountability, governance, and explainability. Recommendations identified in the literature to address present barriers call for a proactive evaluation of MMS, multidisciplinary collaboration, adherence to investigation and validation protocols, transparency and traceability requirements, and guiding standards and frameworks that enhance documentation efforts and support the translation of AI- and ML-based MMS., Conclusions: Resolving barriers to translation is critical for MMS to deliver on expectations, including those barriers identified in this scoping review related to bias, accountability, governance, and explainability. Our findings suggest that transparent strategic documentation, aligning translational science and regulatory science, will support the translation of MMS by coordinating communication and reporting and reducing translational barriers, thereby furthering the adoption of MMS., (©Tracey A Brereton, Momin M Malik, Mark Lifson, Jason D Greenwood, Kevin J Peterson, Shauna M Overgaard. Originally published in the Interactive Journal of Medical Research (https://www.i-jmr.org/), 14.07.2023.)

A woman in her late fifties was admitted to the Family Medicine Inpatient Service directly from Rheumatology clinic for polyarticular pain and erythema with concern for infection. She was taking immunosuppressant medications for a history of multiple autoimmune diseases. Examination showed increasing erythema and tenderness on the upper and lower extremity joints. Histologic evaluation, surgical evaluation, and cultures were consistent with mycobacterium haemophilum infection. Mycobacterium haemophilum is an uncommon opportunistic infection that usually affects immunocompromised patients. The patient was treated with a multi-drug antibiotic regimen for several months due to drug resistance. Although this opportunistic infection is not common it should be considered in the differential of immunocompromised patients with skin and articular symptoms. Treatment outcomes are usually favorable if it caught earlier in the course.

Polymorphonuclear (PMN) leucocytes participate in acute inflammatory pathologies such as acute respiratory distress syndrome (ARDS) following traumatic injury and shock, which also activates the coagulation system systemically. Trauma can prime the PMN nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex for an enhanced respiratory burst, but the relative role of various priming agents in this process remains incompletely understood. We therefore set out to identify mediators of PMN priming during coagulation and trauma-shock and determine whether PMN reactive oxygen species (ROS) generated in this manner could influence organ injury and coagulation. Initial experiments demonstrated that PMN are primed for predominantly extracellular ROS production by products of coagulation, which was abrogated by CD88/C5a receptor(C5aR) inhibition. The importance of this was highlighted further by demonstrating that known PMN priming agents result in fractionally different amounts of extracellular versus intracellular ROS release depending on the agent used. Plasma from trauma patients in haemodynamic shock (n = 10) also primed PMN for extracellular ROS in a C5a-dependent manner, which correlated with both complement alternative pathway activation and thrombin generation. Furthermore, PMN primed by preincubation with products of blood coagulation directly caused loss of endothelial barrier function in vitro that was abrogated by C5aR blockade or NADPH oxidase inhibition. Finally, we show in a murine model of trauma-shock that p47phox knock-out (KO) mice with PMN incapable of generating ROS were protected from inflammatory end-organ injury and activated protein C-mediated coagulopathy. In summary, we demonstrate that trauma-shock and coagulation primes PMN for predominantly extracellular ROS production in a C5a-dependent manner that contributes to endothelial barrier loss and organ injury, and potentially enhances traumatic coagulopathy., (© 2018 British Society for Immunology.)

To evaluate the expression of the Tie2/Tek tyrosine kinase receptor in tumor blood vessels, we examined Tie2lacZ(+)/RAG1(-) mice. There was considerable heterogeneity (Tie2-negative, Tie2-positive, or Tie2-composite blood vessels) in subcutaneous xenografts of human colorectal carcinoma (HCT116; 97.5% Tie2-positive vessels) versus human melanoma (WM115; 75.9% Tie2-positive vessels). Similar patterns of Tie2 expression occurred in abdominal metastases derived from the same cell lines. Immunostaining for endothelial markers and Tie2 revealed that endogenous protein levels corresponded with transgene activity. Endothelial cells were confirmed to be of mouse origin through triple immunofluorescence staining with mouse antiserum to human nuclei, isolectin GS-IB(4), and anti-Tie2. Similar Tie2 heterogeneity was observed in clinical specimens from a variety of human cancers, including malignant melanoma and colorectal carcinoma. We also examined the effect of Tek-Delta Fc anti-angiogenic therapy on tumor growth and Tie2 expression patterns in HCT116 and WM115 subcutaneous xenografts. Tek-Delta induced extensive tumor regression in HCT116 tumors and concomitant reductions in Tie2-expressing blood vessels. However, no significant responses were seen in Tek-Delta-treated WM115 tumors. Thus, vascular heterogeneity of Tie2 expression is cancer-type specific, suggesting that the tumor microenvironment and/or direct cancer cell interactions influence Tie2 endothelial expression.

Studies of murine severe combined immune-deficient (scid/scid) fetuses gestating in transgene-tagged immune competent dams have established high frequencies of transplacental trafficking of nucleated maternal cells. Maternal cells first appeared in thymus at gestation day (gd) 12.5 and were present in more than 90% of late gestation fetuses. Morphologically heterogeneous maternal cells were located predominantly in bone marrow and thymus and also occasionally in liver, spleen, and nonlymphoid organs. We have now evaluated maternal cell chimerism in offspring with normal lymphoid development. Genetically normal blastocysts from random-bred CD1 mice were transferred to C57BL/6J- lacZ transgene-tagged ROSA26 females. Serial sectioning of fetuses followed by histochemistry for lacZ-expressing cells was used to comprehensively define organs containing maternal cells. Fetuses, sectioned in their entirety, had no detectable maternal cells before gd 16.5. Morphologically homogenous, nucleated maternal cells were first present in fetal bone marrow cavities at gd 16.5 and were evident in all offspring in later gestation. Postnatally, maternal cells were also present in bone marrow cavities into adulthood, as determined by lacZ histochemistry and PCR amplification of the maternal transgene. The frequency of maternally derived cells in postnatal bone marrow was increased compared with late gestation, and occasionally, maternal cells were detected in postnatal spleen. The normalcy of maternal cell transfer to genetically immune competent progeny and their long-term engraftment is suggestive of a functional role for maternal cells in offspring.

cDNAs encoding the bovine immunodeficiency virus (BIV) transactivator gene (tat) were cloned from virally infected cells and characterized. BIV expresses two distinct tat mRNAs composed of three exons that are derived by alternative splicing. The BIV tat mRNA splice variants encode Tat proteins of 103 (Tat103) and 108 (Tat108) amino acids. The Tat103 coding region is specified only by exon 2, while that of Tat108 is specified by a truncated exon 2 and the first 30 nt of exon 3. Thus, the first 98 amino acids of each Tat are identical, and have amino terminal, cysteine-rich, conserved core, basic, and carboxyl-terminal domains similar to Tats encoded by primate lentiviruses. BIV-infected bovine cells express a 14-kDa phosphorylated Tat protein identical in size to recombinant Tat expressed in bacteria. BIV Tat was shown to localize exclusively in the nucleoli of virally infected and Tat-expressing cells. Reporter gene assays indicated that Tat103 and Tat108 can strongly transactivate the BIV long terminal repeat (LTR) in virally permissive canine Cf2Th and nonpermissive HeLa and mouse NIH 3T3 cells, but not in permissive lapine EREp cells. However, an intact BIV tat gene is required for viral replication in both Cf2Th and EREp cells. Strong LTR activation by BIV Tat requires a TAR (transactivation responsive) element delimited by viral nt +1 to +31 and the Tat basic domain. BIV Tat strongly cross-transactivates the HIV-1 LTR in a TAR-dependent manner in Cf2Th, but not in EREp, HeLa, or NIH 3T3 cells. In contrast, strong, TAR-dependent cross-transactivation of the BIV LTR by HIV-1 Tat could not be demonstrated in any of these cell types. In Cf2Th cells Tat108 effects a moderately stronger transactivation of the BIV LTR than Tat103, indicative of a functional difference in BIV Tat proteins encoded by the mRNA splice variants. The present studies demonstrate that BIV Tat parallels the primate lentiviral Tats in structure and biochemistry but is not interchangeable with the latter.

Objective: To examine the interaction between synovial fibroblasts and macrophages in the context of cartilage degradation., Methods: An in vitro model of human cartilage degradation was used, in which purified populations of fibroblasts and macrophages were added to a radiolabeled cartilage disc. Cartilage destruction was measured by the percentage of radiolabel release., Results: Fibroblasts, obtained from either rheumatoid arthritis (RA) or osteoarthritis synovial tissue, could mediate cartilage degradation if cocultured with the U937 macrophage cell line. Skin and RA bone marrow fibroblasts had no degradative effect on cartilage. Fibroblast-macrophage contact was not required for cartilage degradation. Cartilage degradation by synovial fibroblasts was inhibited by antibodies to tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and IL-6. Cartilage degradation was almost completely abrogated by a combination of antibodies to TNF alpha and IL-1 beta. Contact between fibroblasts and cartilage was shown to be essential. Antibodies to CD44, but not to intercellular adhesion molecule 1, markedly inhibited cartilage degradation., Conclusion: TNF alpha, IL-1 beta, and IL-6 were involved in the activation of synovial fibroblasts to cause cartilage degradation. Cartilage degradation occurred only when fibroblasts were in contact with cartilage. CD44 was demonstrated to be involved in the fibroblast-cartilage interaction.

It is traditionally held that human IgG4 MoAbs should not deplete target cells in vivo, as this isotype is inactive in a number of in vitro assays that measure effector function. We have previously challenged this dogma, and the current study was designed to investigate the in vivo biological effects in humans of a MoAb of human IgG4 isotype. Nine patients with refractory rheumatoid arthritis (RA) fulfilling ARA criteria, and one with ankylosing spondylitis (AS) received a human IgG4 Campath-1 MoAb (with specificity against the pan-lymphocyte antigen CD52) as part of a two-stage therapeutic protocol. In stage 1, patients received a single dose of this MoAb. Stage 2, starting 48 h later, comprised a 5-day course of a human IgG1 Campath-1 MoAb with identical V-region (CAMPATH-1H), as previously used in the management of RA patients. The intervening 48 h provided a window of opportunity to monitor the biological effects of the IgG4 MoAb for comparison with the IgG1. The two MoAbs were also compared for in vitro biological activity. IgG4 depleted peripheral blood lymphocytes (PBL), albeit less efficiently than IgG1. It produced a first-dose reaction of similar intensity, although associated circulating tumour necrosis factor-alpha (TNF-alpha) levels were lower. TNF-alpha release from whole blood in vitro was also greater with the IgG1 MoAb. The study design did not permit conclusions to be drawn regarding therapeutic efficacy of the IgG4 MoAb. In summary, a human IgG4 Campath-1 MoAb depletes target cells in vivo. Importantly, this study demonstrates for the first time in humans that in vitro assays may not predict the in vivo effector function of therapeutic MoAbs.

A complete cDNA clone encoding the rat JAK2 protein tyrosine kinase was isolated from an Nb2-SP (rat pre-T lymphoma cell line) cDNA library. The nucleotide (nt) and deduced amino acid (aa) sequences for this clone were determined and an open reading frame of 3399 bp, encoding a protein of a deduced mass of 130 kDa, was found. The coding regions of the rat and murine Jak2 clones share 93.4% nt identity and 97.1% aa identity. Northern analysis demonstrated that the 5-kb mRNA is highly abundant in brain and spleen, less abundant in skeletal muscle and testis, and detectable in kidney, heart, lung and liver. Translation of the rat Jak2 mRNA in rabbit reticulocytes results in a protein which is specifically immunoprecipitated by antibodies (Ab) recognizing JAK2, but not by Ab recognizing JAK1.

One of the six putative accessory genes of bovine immunodeficiency virus (BIV) is similar to those identified as rev in the human immunodeficiency virus and visna virus genomes. To further analyze the BIV rev gene locus, protein, and function, rev cDNAs were cloned and characterized. BIV rev mRNA is derived from the full-length transcript by multiple splicing events and consists of three exons, including the untranslated leader sequence and two coding exons. BIV rev cDNA was expressed in bacteria and in a mammalian in vitro translation expression system. A 23-kDa Rev protein (p23rev) was immunologically detected in lysates from both systems by using an antiserum made to a synthetic Rev peptide. Recombinant p23rev made in bacteria was purified and used to make a polyvalent antiserum. Antisera to Rev peptide and recombinant p23rev immunoprecipitated p23rev from BIV-infected mammalian cells but not from virions. A mammalian expression vector using the BIV rev cDNA was constructed; p23rev was immunoprecipitated with anti-Rev serum from 32P-labeled lysates of monkey cells transfected with this plasmid, demonstrating that BIV Rev is phosphorylated. Immunofluorescence and immunoelectron microscopy with anti-BIV Rev antisera localized Rev in the nucleus and, particularly, in the nucleoli of BIV-infected cells. In functional studies, the expression of BIV Rev was shown to positively regulate the appearance both of Gag protein, which is translated from the unspliced primary viral transcript, and of singly spliced env mRNA but not that of the multiply spliced tat mRNA. These results demonstrate that BIV Rev activity correlates with the known function of lentivirus Rev proteins.

The percent (%) peak oxygen uptake (VO2) and % peak heart rate (HR) relationships were determined in 13 persons with high (T1-T6) and 14 persons with low lesion (T7-T12) spinal cord injured paraplegia (SCI PARA) and 15 nonimpaired subjects during graded arm crank (AC) tests to exhaustion. Subjects were instructed to maintain a target cadence of 60 rpm on a modified electronically braked leg cycle ergometer. After 3 min of unloaded cranking, power output (PO) was increased by 8-16 W.min-1. VO2 and HR were determined via open-circuit spirometry and 12-lead ECG, respectively. Absolute HR and VO2 values for each PO were converted to % peak HR and % peak VO2 values. Linear regression slopes describing individual % peak HR and % peak VO2 relationships were calculated and compared between groups with one-way ANOVA. No significant differences (P > 0.05) were noted between the mean (+/- SD) regression slopes for persons with high lesion SCI PARA (1.48 +/- 0.21), persons with low lesion SCI PARA (1.48 +/- 0.26), and nonimpaired subjects (1.53 +/- 0.29). Regression equations derived using all data points within each group were as follows: High lesion SCI PARA: y = 1.3x-37.0, R = 0.85 Low lesion SCI PARA: y = 1.23x-30.9, R = 0.88 Nonimpaired subjects: y = 1.41x-46.2, R = 0.95 (y = % peak VO2, x = % peak HR). These equations are similar to those previously reported for nonimpaired men and women and cardiac patients during AC and leg cycle ergometry.(ABSTRACT TRUNCATED AT 250 WORDS)

The bovine immunodeficiency-like virus (BIV) genome contains the obligatory structural genes of all retroviruses and, in addition, the complex central region of lentiviruses; this novel region may code for at least five nonstructural/regulatory genes in BIV (K.J.Garvey, M.S. Oberste, J.E. Elser, M.J. Braun, and M.A. Gonda, Virology 175:391-409, 1990). As a prelude to determining the function of these novel open reading frames, the transcriptional pattern of BIV was studied by Northern analysis of RNA from BIV-infected cells. Five size classes of BIV-specific RNAs of 8.5, 4.1, 3.8, 1.7, and 1.4 kb were detected. The 8.5-kb RNA contains sequences from all regions of the genome; it is the virion RNA and probably serves as the gag-pol transcript as well. By using gene-specific probes, subgenomic viral RNAs of 3.8, 1.7, and 1.4 kb were tentatively identified as the env, tat, and rev spliced messages, respectively. The 4.1-kb RNA could not be unambiguously identified but may encode vif. The hybridization patterns of the putative tat and rev mRNAs suggest that they are the products of multiple splicing events. Discrete transcripts for the BIV W and Y central region open reading frames were not defined. The characterization of partial cDNA clones has permitted the mapping of the env and putative rev splice junctions.

Clinical and nonclinical isolates of the lactose-positive Vibrio vulnificus were compared with Vibrio strains isolated from lesions on eels (Anguilla japonica) cultured commercially in Japan. Strains were compared phenotypically and antigenically, for pathogenicity to mice and eels, and for genetic relatedness. The strains isolated from diseased eels differed phenotypically from the original species description of V. vulnificus in that they were negative for indole production, ornithine decarboxylase activity, growth at 42 degrees C, and acid production from mannitol and sorbitol. No relationship between the surface antigens of V. vulnificus strains from environmental and clinical sources and the strains from diseased eels was observed. Typical V. vulnificus strains and the eel isolates were pathogenic to mice; however, only those strains originally isolated from diseased eels were found to be pathogenic to eels. Results of DNA-DNA competition experiments revealed that there was greater than 90% relative reassociation between clinical and nonclinical V. vulnificus and strains from diseased eels. Based on the results of the DNA-DNA competition experiments, we conclude that the strains isolated from diseased eels were V. vulnificus; however, the differences in phenotypic characteristics and eel pathogenicity indicated that these strains represent a different biogroup. Therefore, we propose that strains phenotypically similar to the type strain of the species (ATCC 27562) be classified as V. vulnificus biogroup 1 and the strains phenotypically similar to those isolated from diseased eels be classified as V. vulnificus biogroup 2 represented by the reference strain ATCC 33148.