Anticipation or avoidance: internal medicine resident experiences performing invasive bedside procedures.

Background: Internal Medicine (IM) residents are required to perform bedside procedures for diagnostic and therapeutic purposes. Residents' experiences with procedures vary widely, for unclear reasons. Objective: To explore IM residents' experiences with performing bedside procedures and to identify barriers and facilitators to obtaining sufficient experience. Methods: Using an inductive, thematic approach, we conducted five individual semi-structured interviews and one focus group with seven IM residents (12 residents in total) during the 2017-2018 academic year at a Canadian tertiary care centre. We used iterative, open-ended questions to elicit residents' experiences, and barriers and facilitators, to performing bedside procedures. Transcripts were analyzed for themes using Braun and Clarke's method. Results: We identified four themes 1) Patient-specific factors such as body habitus and procedure urgency; 2) Systems factors such as time constraints and accessibility of materials; 3) Faculty factors including availability to supervise, comfort level, and referral preferences, and 4) Resident-specific factors including preparation, prior experiences, and confidence. Some residents expressed procedure-related anxiety and avoidance. Conclusion: Educational interventions aimed to improve procedural efficiency and ensure availability of supervisors may help facilitate residents to perform procedures, yet may not address procedure-related anxiety. Further study is required to understand better how procedure-averse residents can gain confidence to seek out procedures.

Contexte: Les résidents en médecine interne (MI) sont amenés à effectuer des procédures au chevet du patient à des fins diagnostiques et thérapeutiques. Les expériences des résidents en lien avec ces procédures varient considérablement, et ce sans raison évidente. Objectif: Explorer les expériences des résidents en MI lors des procédures effectuées au chevet du patient et identifier les facteurs qui entravent ou, au contraire, facilitent l'acquisition d'une expérience suffisante. Méthodes: En utilisant une approche inductive et thématique, nous avons mené cinq entrevues individuelles semi-structurées et un groupe de discussion avec sept résidents de MI (12 résidents au total) dans un centre de soins tertiaires canadien au cours de l'année universitaire 2017-2018. Nous avons utilisé des questions ouvertes itératives pour recueillir les expériences des résidents lors des procédures faites au chevet du patient, ainsi qu'identifier les obstacles et les facilitateurs de ces interventions. Les transcriptions d'entrevues ont été analysées pour identifier les thèmes émergents selon la méthode de Braun et Clarke. Résultats: Nous avons relevé quatre thèmes : 1) les facteurs spécifiques aux patients comme la morphologie du patient et l'urgence de la procédure; 2) les facteurs systémiques comme les contraintes de temps et l'accessibilité du matériel; 3) les facteurs liés corps professoral, notamment leur disponibilité pour superviser, leur niveau de confort et leur propension à orienter certaines procédures vers d'autres collègues; et 4) les facteurs spécifiques aux résidents, à savoir la préparation, les expériences antérieures et la confiance. Certains résidents ont exprimé vivre de l'anxiété face aux procédures et de l'évitement. Conclusion: Les initiatives éducatives visant à améliorer l'efficacité des procédures et à assurer la disponibilité de superviseurs peuvent faciliter leur réalisation par les résidents, mais elles peuvent ne pas atténuer l'anxiété reliée aux procédures. Des études supplémentaires sont nécessaires pour mieux comprendre comment accroître la confiance des résidents qui sont réticents face aux procédures au chevet du patient.

Life on Call: Perspectives of Junior and Senior Internal Medicine Residents.

PURPOSE: Models of daytime and nighttime on-call responsibilities for residents vary across internal medicine training programs, but there are few data regarding residents' perceptions of their on-call experiences. The authors sought to understand what residents perceive as the benefits and detriments of 24-hour, in-house call, a perspective instrumental to informing change. METHOD: The authors conducted in-depth individual interviews and focus groups between December 2018 and March 2019 with 17 internal medicine residents from postgraduate years 1, 2, and 3 at the University of Toronto about their on-call experiences. Using constructivist grounded theory, the authors developed a framework to understand the residents' perceived benefits and drawbacks of 24-hour in-house call. RESULTS: Residents' experiences on call were grouped into 7 themes regarding negative and positive aspects of call. Participants reported multidimensional fatigue related to call, including decision fatigue, emotional fragility and lability, and loss of empathy, and also reported that call adversely affected their personal lives. Residents expressed conflicting opinions as to whether prolonged duty hours affected patient outcomes. In contrast, residents also expressed benefits to call, including that overnight call led to increased autonomy and decision-making skills and provided preparation for future careers as independent internists. They described developing camaraderie and a sense of belonging to a team with coresidents overnight. Lastly, residents described occupying different roles during regular duty hours and while on call-daytime roles revolved around follow-up of previously admitted patients and administrative tasks, while overnight duties centered on initial workup and medical stabilization of referred patients. CONCLUSIONS: Understanding the nuanced phenomenon of being on call from the perspective of those who live through it is a critical step in creating evidence-based educational policies. New call models should emphasize resident autonomy and decision making and should include a consideration of residents' perceived differences between daytime and on-call roles.

Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis.

OBJECTIVE: To compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older. DESIGN: Systematic review with bayesian meta-analysis and network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Experimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death. RESULTS: 27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively). CONCLUSIONS: Using the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites. PROTOCOL REGISTRATION: Prospero CRD42017056389.

Pasteurella multocida non-native joint infection after a dog lick: A case report describing a complicated two-stage revision and a comprehensive review of the literature.

Prosthetic joint infections (PJIs) are commonly caused by pathogens such as Staphylococcus aureus and coagulase-negative staphylococci; however, other microbial etiologies and specific risk factors are increasingly recognized. Pasteurella multocida is a Gram-negative coccobacillus that is part of the normal oral flora in many animals, and is particularly common in dogs and cats. PJIs caused by P multocida have been reported only rarely in the literature and typically occur in the context of an animal bite or scratch. The present article describes a P multocida joint infection that occurred after a dog lick and complicated a two-stage revision arthroplasty. A comprehensive review of the literature regarding P multocida PJIs follows.

Les infections sur prothèse articulaire (IPA) sont souvent causées par des pathogènes comme le Staphylococcus aureus et les staphylocoques à coagulase négative. Cependant, on constate de plus en plus d'autres étiologies microbiennes et de facteurs de risque particuliers. Le Pasteurella multocida, un coccobacille à Gram négatif qui fait partie de la flore orale normale de nombreux animaux, est particulièrement courant chez les chiens et les chats. Peu d'IPA causées par le P multocida sont signalées dans les publications scientifiques, mais elles se produisent surtout après une morsure ou une griffure d'animal. Le présent article décrit une infection à P multocida qui s'est manifestée après que l'articulation a été léchée par un chien et une arthroplastie de révision compliquée en deux étapes. Une analyse bibliographique approfondie de l'IPA à P multocida suit.

Interventions for post-infectious irritable bowel syndrome: a systematic review of treatment efficacy.

BACKGROUND: Post-infectious irritable bowel syndrome (PI-IBS) due to traveler's diarrhea is the second most common illness seen in post-travel clinics, yet its optimal management remains unknown. We performed a systematic review to evaluate treatment efficacy in PI-IBS. METHODS: We searched Medline, EMBASE, LILACS, CINAHL, CAB abstracts, and the Cochrane Library to February 3, 2014 for intervention studies of the pharmacologic and non-pharmacologic management of PI-IBS and examined the evidence according to a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scale. RESULTS: Of 336 records, 9 studies were included. Eight studies of pharmacologic interventions examined 5 agents (mesalazine or mesalamine, ondansetron, prednisolone, cholestyramine, and metronidazole). One study examined the non-pharmacologic intervention of different infant nutritional formulas following acute gastroenteritis. The quality of the evidence to date was low, with small sample size (fewer than 50 participants) and short duration of follow-up. Overall, the efficacy of pharmacological treatment ranged from no benefit (ondansetron and prednisolone) to moderately beneficial (cholestyramine and metronidazole). The evidence for mesalazine was equivocal: one study showed benefit, two others showed none. CONCLUSIONS: Heterogeneity in outcome measures and low strength of evidence preclude recommendations on the optimal management of PI-IBS by a specific agent. More comparative intervention research into PI-IBS treatment is needed for consistent best practice in PI-IBS management. Clinicians may elect to pursue therapeutic trials of mesalazine, cholestyramine, or metronidazole in individual patients, but should be aware that data supporting the efficacy of these agents is limited.

Enterohemorrhagic Escherichia coli Infections and the Hemolytic-Uremic Syndrome.

Enterohemorrhagic Escherichia coli (EHEC; Shiga toxin/verotoxin-producing E. coli) can cause bloody diarrhea and the hemolytic-uremic syndrome (HUS), typically following consumption of contaminated food (including ground beef, leafy greens, and sprouts) and water. Often associated with foodborne outbreaks, EHEC possess unique virulence factors that facilitate effective colonization of the human gastrointestinal tract and subsequent release of Shiga toxin. This article reviews the epidemiology, pathogenesis, clinical presentation, treatment, and prevention of EHEC infections, focusing on E. coli O157:H7, the serotype most common in North America, and E. coli O104:H4, the serotype responsible for the EHEC outbreak in Germany in 2011.

Dysregulation of angiopoietin 1 and 2 in Escherichia coli O157:H7 infection and the hemolytic-uremic syndrome.

Escherichia coli O157:H7-associated hemolytic-uremic syndrome (HUS) is characterized by profound prothrombotic abnormalities. Endothelial dysfunction, manifested as dysregulation of angiopoietins 1 and 2 (Ang-1/2), could underlie HUS pathophysiology. We measured Ang-1/2 in 77 children with E. coli O157:H7 infection. Ang-1, Ang-2, and the Ang-2/Ang-1 ratio were significantly different in HUS vs the pre-HUS phase of illness or uncomplicated infection. Angiopoietin dysregulation preceded HUS and worsened as HUS developed. In vitro exposure of human microvascular endothelial cells to Shiga toxin recapitulated the in vivo observations. Angiopoietin regulation is profoundly affected before and during HUS, reflecting that subclinical endothelial dysfunction precedes overt microangiopathy.

Biomarkers of endothelial activation/dysfunction in infectious diseases.

Endothelial dysfunction contributes to the pathogenesis of a variety of potentially serious infectious diseases and syndromes, including sepsis and septic shock, hemolytic-uremic syndrome, severe malaria, and dengue hemorrhagic fever. Because endothelial activation often precedes overt endothelial dysfunction, biomarkers of the activated endothelium in serum and/or plasma may be detectable before classically recognized markers of disease, and therefore, may be clinically useful as biomarkers of disease severity or prognosis in systemic infectious diseases. In this review, the current status of mediators of endothelial cell function (angiopoietins-1 and -2), components of the coagulation pathway (von Willebrand Factor, ADAMTS13, and thrombomodulin), soluble cell-surface adhesion molecules (soluble E-selectin, sICAM-1, and sVCAM-1), and regulators of vascular tone and permeability (VEGF and sFlt-1) as biomarkers in severe infectious diseases is discussed in the context of sepsis, E. coli O157:H7 infection, malaria, and dengue virus infection.

The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome in humans and mice.

Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition. It often occurs after gastrointestinal infection with E. coli O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury. Stx-mediated changes in endothelial phenotype have been linked to the pathogenesis of HUS. Here we report our studies investigating Stx-induced changes in gene expression and their contribution to the pathogenesis of HUS. Stx function by inactivating host ribosomes but can also alter gene expression at concentrations that minimally affect global protein synthesis. Gene expression profiling of human microvascular endothelium treated with Stx implicated a role for activation of CXCR4 and CXCR7 by their shared cognate chemokine ligand (stromal cell-derived factor-1 [SDF-1]) in Stx-mediated pathophysiology. The changes in gene expression required a catalytically active Stx A subunit and were mediated by enhanced transcription and mRNA stability. Stx also enhanced the association of CXCR4, CXCR7, and SDF1 mRNAs with ribosomes. In a mouse model of Stx-mediated pathology, we noted changes in plasma and tissue content of CXCR4, CXCR7, and SDF-1 after Stx exposure. Furthermore, inhibition of the CXCR4/SDF-1 interaction decreased endothelial activation and organ injury and improved animal survival. Finally, in children infected with E. coli O157:H7, plasma SDF-1 levels were elevated in individuals who progressed to HUS. Collectively, these data implicate the CXCR4/CXCR7/SDF-1 pathway in Stx-mediated pathogenesis and suggest novel therapeutic strategies for prevention and/or treatment of complications associated with E. coli O157:H7 infection.

Colony-stimulating factors in the prevention and management of infectious diseases.

Colony-stimulating factors (CSFs) are attractive adjunctive anti-infective therapies. Used to enhance innate host defenses against microbial pathogens, the myeloid CSFs increase absolute numbers of circulating innate immune effector cells by accelerating bone marrow production and maturation, or augment the function of those cells through diverse effects on chemotaxis, phagocytosis, and microbicidal functions. This article summarizes the evidence supporting the accepted clinical uses of the myeloid CSFs in patients with congenital or chemotherapy-induced neutropenia, and presents an overview of proposed and emerging uses of the CSFs for the prevention and treatment of infectious diseases in other immunosuppressed and immunocompetent patient populations.

Systemic dysregulation of angiopoietin-1/2 in streptococcal toxic shock syndrome.

Streptococcal toxic shock syndrome (STSS) is characterized by diffuse vascular leak resulting from widespread endothelial activation. Angiopoietin-1 and -2 (Ang-1 and Ang-2), which are important regulators of endothelial quiescence and activation, respectively, are dysregulated in certain diseases that are associated with endothelial dysfunction, but they have not been previously investigated in STSS. Plasma Ang-1 and Ang-2 concentrations were measured in 37 patients with invasive streptococcal infection with and without concurrent STSS. Greater angiopoietin dysregulation (decreased Ang-1 and increased Ang-2) occurred in STSS than in invasive infection without shock; dysregulation decreased with convalescence. These results suggest that systemic Ang-1 and Ang-2 dysregulation is associated with disease severity in invasive streptococcal infection and that plasma levels of Ang-1 and Ang-2 may serve as clinically informative biomarkers in STSS.

A twist on Lyme: the challenge of diagnosing European Lyme neuroborreliosis.

Lyme neuroborreliosis is a tick-borne illness with central and peripheral nervous system manifestations. Clinical features and methods for accurate diagnosis differ across world regions owing to different causative Borrelia species. The importance of these distinctions is highlighted by a 12-year-old Canadian girl who acquired Lyme neuroborreliosis in Europe.

Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and other immunomodulatory therapies for the treatment of infectious diseases in solid organ transplant recipients.

PURPOSE OF REVIEW: Infections continue to cause significant morbidity and mortality in SOT recipients despite major advances in immunosuppressive and antimicrobial regimens. Immunomodulatory cytokines provide a potential means to augment the host immune response to infection. This review will focus on cytokine therapy for the prophylaxis and treatment of infections in solid organ transplant recipients, and will speculate on the potential for further advances in the field. RECENT FINDINGS: In kidney and liver transplant recipients, granulocyte colony-stimulating factor (G-CSF) has been used successfully to reverse ganciclovir-induced neutropenia or cytomegalovirus-induced neutropenia. Although G-CSF also reversed corticosteroid-induced suppression of the neutrophil respiratory burst in vitro, prophylactic G-CSF failed to reduce infections or mortality in nonneutropenic solid organ transplant recipients. Published clinical experience with granulocyte-macrophage colony-stimulating factor (GM-CSF) in this population has been limited to case reports and a small case series, whereas the use of macrophage colony-stimulating factor (M-CSF) or interferon-gamma (IFN-gamma) has not been systematically investigated in controlled clinical trials. SUMMARY: Despite encouraging results in vitro and in preclinical models, immunomodulatory cytokines have not met expectations when administered to SOT recipients. Nonetheless, the principle of selective enhancement of innate immunity for the prevention and treatment of infections in this patient population has promise and warrants further study.

Posaconazole: A new agent for the prevention and management of severe, refractory or invasive fungal infections.

Posaconazole is the newest antifungal agent to be approved for use in Canada. With excellent in vitro activity against a broad spectrum of yeasts and filamentous fungi, as well as having a well-tolerated oral formulation, posaconazole offers many potential advantages. Of particular interest are its seemingly lower potential for cross-resistance with other azoles and its activity (unique among oral antifungal agents) against the zygomycetes. As the incidence of both common and uncommon fungal infections increases commensurate with the growing population of immunocompromised individuals, posaconazole may ultimately become an important therapeutic option. The present article reviews the in vitro and in vivo data describing its activity, and focuses on both the proven and the potential clinical applications of this new triazole agent.