The Use and Monitoring of Oral Antibiotics for Treatment of Prosthetic Joint Infections.

Intravenous antibiotic therapy remains necessary for many patients with prosthetic joint infections. Intravenous therapies may be used for short durations before switching to oral regimens or may be used for the entirety of therapy. Factors to consider in intravenous antibiotic selection include pathogen factors such as resistance profiles, host factors such as allergies, and drug factors including how difficult the selected agent would be to administer in the outpatient setting. Monitoring of prolonged intravenous therapy in the outpatient setting requires weekly monitoring of labs with specific labs required to monitor certain antibiotics. This narrative review assesses the appropriate duration, antimicrobial selection by pathogen, and monitoring parameters for intravenous antibiotic treatment of prosthetic joint infections. (Journal of Surgical Orthopaedic Advances 30(4):256-262, 2021).

Considerations for Intravenous Antibiotic Treatment of Prosthetic Joint Infections.

Intravenous antibiotic therapy remains necessary for many patients with prosthetic joint infections. Intravenous therapies may be used for short durations before switching to oral regimens or may be used for the entirety of therapy. Factors to consider intravenous antibiotic selection include pathogen factors such as resistance profiles, host factors such as allergies, and drug factors including how difficult the selected agent would be to administer in the outpatient setting. Monitoring of prolonged intravenous therapy in the outpatient setting requires weekly monitoring of labs with specific labs required to monitor certain antibiotics. This narrative review assesses the appropriate duration, antimicrobial selection by pathogen, and monitoring parameters for intravenous antibiotic treatment of prosthetic joint infections. (Journal of Surgical Orthopaedic Advances 30(4):243-248, 2021).

Left-sided infective endocarditis in persons who inject drugs.

PURPOSE: The purpose of this study was to describe left-sided infective endocarditis (LSIE) in persons who inject drugs (PWID) and compare that group to PWID with non-LSIE and to non-PWID with LSIE. METHODS: Retrospective single-center study of adult IE patients from 2011 to 2018. RESULTS: Of the 333 patients in our cohort, 54 were PWID with LSIE, 75 were PWID with non-LSIE, and 204 were non-PWID with LSIE. When comparing LSIE vs non-LSIE in PWID, the LSIE group was older (median age 35 vs 28.5, p < 0.01), had fewer S. aureus infections (59% vs 92%, p < 0.01), was more likely to have cardiac surgery (31% vs 13%, p < 0.01), and had a higher 10-week mortality (22% vs 5%, p < 0.01). When comparing PWID with LSIE to non-PWID with LSIE, the PWID group were younger (median age 35 vs 46, p < 0.01); had more frequent multi-valve involvement (33% vs 19%, p = 0.04), Staphylococcus aureus infections (54% vs 27%, p < 0.01), and previous IE (24% vs 8%, p < 0.01); and experienced more strokes (54% vs 31%, p < 0.01). Ten-week mortality was similar for LSIE in both PWID and non-PWID (24% vs 20%, p = 0.47). CONCLUSIONS: LSIE in PWID is not uncommon. Compared to non-LSIE in PWID, valve surgery is more common and mortality is higher. For reasons that are unclear, stroke is more frequent in LSIE in PWID than in non-PWID with LSIE but mortality is no different.

Hospitalizations for Endocarditis and Associated Health Care Costs Among Persons with Diagnosed Drug Dependence - North Carolina, 2010-2015.

Opioid dependence and overdose have increased to epidemic levels in the United States. The 2014 National Survey on Drug Use and Health estimated that 4.3 million persons were nonmedical users of prescription pain relievers (1). These users are 40 times more likely than the general population to use heroin or other injection drugs (2). Furthermore, CDC estimated a near quadrupling of heroin-related overdose deaths during 2002-2014 (3). Although overdose contributes most to drug-associated mortality, infectious complications of intravenous drug use constitute a major cause of morbidity leading to hospitalization (4). In addition to infections from hepatitis C virus (HCV) and human immunodeficiency virus (HIV), injecting drug users are at increased risk for acquiring invasive bacterial infections, including endocarditis (5,6). Evidence that hospitalizations for endocarditis are increasing in association with the current opioid epidemic exists (7-9). To examine trends in hospitalizations for endocarditis among persons in North Carolina with drug dependence during 2010-2015, data from the North Carolina Hospital Discharge database were analyzed. The incidence of hospital discharge diagnoses for drug dependence combined with endocarditis increased more than twelvefold from 0.2 to 2.7 per 100,000 persons per year over this 6-year period. Correspondingly, hospital costs for these patients increased eighteenfold, from $1.1 million in 2010 to $22.2 million in 2015. To reduce the risk for morbidity and mortality related to opioid-associated endocarditis, public health programs and health care systems should consider collaborating to implement syringe service programs, harm reduction strategies, and opioid treatment programs.

Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia.

PURPOSE: To report the use of intranasal dexmedetomidine, an α2-adrenergic agonist for the acute treatment of refractory adrenergic crisis in patients with familial dysautonomia. METHODS: Case series. RESULTS: Three patients with genetically confirmed familial dysautonomia (case 1: 20-year-old male; case 2: 43-year-old male; case 3: 26-year-old female) received intranasal dexmedetomidine 2 mcg/kg, half of the dose in each nostril, for the acute treatment of adrenergic crisis. Within 8-17 min of administering the intranasal dose, the adrenergic crisis symptoms abated, and blood pressure and heart rate returned to pre-crises values. Adrenergic crises eventually resumed, and all three patients required hospitalization for investigation of the cause of the crises. CONCLUSIONS: Intranasal dexmedetomidine is a feasible and safe acute treatment for adrenergic crisis in patients with familial dysautonomia. Further controlled studies are required to confirm the safety and efficacy in this population.

Sporadic Creutzfeldt-Jakob Disease Initially Presenting With Posterior Reversible Encephalopathy Syndrome: A Case Report.

INTRODUCTION: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal neurodegenerative condition caused by prion proteins. Cortical and subcortical diffusion-weighted imaging restriction on magnetic resonance imaging (MRI) is associated with sCJD. Posterior reversible encephalopathy syndrome (PRES) results from impaired vessel autoregulation due to an identifiable trigger, which is associated with subcortical fluid-attenuated inversion recovery changes on MRI. We report a case of sCJD initially presenting with PRES. CASE REPORT: A 70-year-old woman presented to an outside hospital with progressive confusion and difficulty in managing activities of daily living. Initial examination revealed stuporous mental state and stimulus-induced myoclonus. MRI revealed bilateral subcortical occipital lobe T2-fluid-attenuated inversion recovery hyperintensities without contrast enhancement suggestive of PRES. Electroencephalogram (EEG) revealed frequent generalized periodic discharges meeting criteria for nonconvulsive status epilepticus. Clinical examination and EEG did not improve despite escalating antiseizure medications. Initial lumbar puncture was unremarkable. She was transferred to our hospital with a presumptive diagnosis of PRES, although there was no clear trigger. Continuous EEG revealed ongoing generalized periodic discharges with myoclonic activity meeting criteria for myoclonic seizures that were refractory to multiple antiseizure medications. Repeat MRI showed resolution of PRES but revealed subtle diffuse cortical diffusion-weighted imaging restriction. Repeat lumbar puncture was performed and 14-3-3 and real-time quaking-induced conversion returned positive, confirming sCJD. CONCLUSIONS: This case reports highlights that sCJD can present with neuroimaging consistent with PRES. The diagnosis of sCJD should be considered in patients with PRES who continue to show neurological decline despite optimal management and radiographic improvement of PRES on MRI. Further research is needed to identify a pathophysiological relationship between these clinical phenotypes.

Improved adherence to colposcopy through nurse-led telephone counselling and multifaceted patient support.

OBJECTIVES: In 2009, an on-site diagnostic colposcopy clinic was established within a large, urban sexual health clinic to enhance follow-up of abnormal cervical cancer screening among vulnerable women, including those who are uninsured. This service model uses a family physician colposcopist and a colposcopy nurse who provides pre-visit counselling, telephone reminders, patient-tailored ongoing support during the diagnostic process, and tracking of missed appointments. This study examined whether this program was associated with improved adherence to the first colposcopy visit after an abnormal Papanicolau smear among a high needs population. METHODS: We conducted a retrospective chart review of women referred for colposcopy between January 2007 and September 2010, and examined non-adherence before (pre-group) and after (post-group) establishment of the on-site program. Univariable and multivariable logistic regression was used to examine patient and clinical factors associated with non-adherence. RESULTS: Six hundred eighty-five women were referred during the study period, with 302 in the pre-group and 383 in the post-group. Non-adherence to the first colposcopy visit fell from 13% to 4% after institution of the on-site service. Pre-group status, cervical screening performed at an abortion-related visit (as opposed to a contraception or cervical screening visit), parity ≥ 1 and younger age were all associated with non-adherence in the multivariable analysis. CONCLUSION: An on-site colposcopy service that incorporated multifaceted, client-tailored support throughout the diagnostic process significantly reduced non-attendance for an initial colposcopy visit in an urban sexual health clinic population. Broader adoption of this model could improve effectiveness of cervical cancer screening programs. However, future research should determine which specific elements of the model are more important in influencing adherence rates.

Objectifs : En 2009, une clinique de colposcopie diagnostique sur place a été mise sur pied au sein d'une importante clinique de santé sexuelle en milieu urbain, en vue d'améliorer le suivi des résultats anormaux de dépistage du cancer du col utérin obtenus par des femmes vulnérables, y compris les femmes n'étant pas couvertes par le régime d'assurance-santé. Ce modèle de service fait appel à un médecin de famille-colposcopiste et à une infirmière spécialisée en colposcopie qui offre des services de counseling préconsultation, des rappels téléphoniques et un soutien continu et adapté à chaque patiente au cours du processus diagnostique, en plus d'effectuer le suivi des rendez-vous manqués. Cette étude s'est penchée sur la question de savoir si ce programme était associé à une amélioration de l'observance du premier rendez-vous en colposcopie à la suite de l'obtention d'un résultat anormal de frottis de Papanicolaou, au sein d'une population présentant des besoins élevés. Méthodes : Nous avons mené une analyse rétrospective des dossiers des femmes orientées en colposcopie entre janvier 2007 et septembre 2010, et examiné la non-observance avant (pré-groupe) et après (post-groupe) la mise sur pied du programme sur place. Une régression logistique univariée et multivariée a été utilisée pour examiner les facteurs cliniques et liés aux patientes qui étaient associés à la non-observance. Résultats : Six cent quatre-vingt-cinq femmes ont été orientées en colposcopie au cours de la période d'étude (302 au sein du pré-groupe et 383 au sein du post-groupe). La non-observance de la première consultation en colposcopie est passée de 13 % à 4 % à la suite de la mise sur pied du service sur place. Le fait de faire partie du pré-groupe, le dépistage cervical mené dans le cadre d'une consultation liée à un avortement (par opposition à une consultation liée à la contraception ou au dépistage cervical), la parité ≥ 1 et le jeune âge ont tous été associés à la non-observance dans le cadre de l'analyse multivariée. Conclusion : La mise sur pied d'un service de colposcopie sur place ayant incorporé un soutien diversifié et adapté aux clientes tout au long du processus diagnostique a entraîné une baisse importante de la non-observance de la consultation initiale en colposcopie, au sein d'une population desservie par une clinique de santé sexuelle en milieu urbain. L'adoption à grande échelle de ce modèle pourrait améliorer l'efficacité des programmes de dépistage du cancer du col utérin. Toutefois, d'autres recherches devraient être menées pour identifier les éléments du modèle qui influencent le plus les taux d'observance.

Strokes in Patients With Injection Drug Use and Tricuspid Valve Endocarditis - A Case Series.

Research Design: In this study, we describe patients from a tertiary care safety-net hospital endocarditis registry with tricuspid valve infective endocarditis (TVIE), and concomitant acute or subacute ischemic stroke predominantly associated with injection drug use (IDU). We retrospectively obtained data pertinent to neurologic examinations, history of injection drug use (IDU), blood cultures, transthoracic/transesophageal echocardiography (TTE/TEE), neuroimaging, and Modified Rankin Scale (mRS) scores at discharge. Only those patients with bacteremia, tricuspid valve vegetations, and neuroimaging consistent with acute to subacute ischemic infarction and microhemorrhages in two cases were included in this series. Results: Of 188 patients in the registry, 66 patients had TVIE and 10 of these were complicated by ischemic stroke. Neurologic symptoms were largely non-specific, eight patients had altered mental status and only 3 had focal deficits. Nine cases were associated with IDU. Two patients had evidence of a patent foramen ovale on echocardiography. Blood cultures grew S. aureus species in 9 of the patients, all associated with IDU. Three patients died during hospitalization. The mRS score at discharge for survivors ranged 0-4. Conclusions: Patients with strokes from TVIE had heterogeneous presentations and putative mechanisms. We noted that robust neuroimaging is lacking for patients with TVIE from IDU and that such patients may benefit from neuroimaging as a screen for strokes to assist peri-operative management. Further inquiry is needed to elucidate stroke mechanisms in these patients.

Non-Cardiac Conditions that Mimic Cardiac Symptoms in Athletes.

When considering the variety of complaints an athlete can present with, chest pain is arguably the most concerning given the potential for catastrophic outcomes. Luckily, these do not comprise the majority of cases, and indeed, are quite rare. The bulk of presentations of athletes with chest pain are due to musculoskeletal, gastrointestinal, and pulmonary causes. Each and every healthcare provider who works closely with athletes must have a thorough understanding of contributing conditions that present as chest pain. Here, we explore some of the more prevalent causes of non-cardiac chest pain, classic presentations, and management considerations.

International Classification of Diseases (ICD) Codes Fail to Accurately Identify Injection Drug Use Associated Endocarditis Cases.

OBJECTIVES: Infective endocarditis (IE) secondary to injection drug use (IDU-IE) is a disease with high morbidity, cost, and rapid demographic evolution. Studies frequently utilize combinations of International Statistical Classification of Diseases (ICD) codes to identify IDU-IE cases in electronic medical records. This is a validation of this identification strategy in a US cohort. METHODS: Records from January 1, 2004 to September 31, 2015 for those aged ≥18yo with any ICD-coded IE encounter (inpatient or outpatient) were retrieved from the electronic medical record and then manually reviewed and classified as IDU-IE by strict and inclusive criteria. This registry was then used to assess the diagnostic accuracy of 10 identification algorithms that combined substance use, hepatitis C, and IE ICD codes. RESULTS: IE was present in 629 of the 2055 manually reviewed records; 109 reported IDU within 3 months of IE diagnosis and an additional 32 during their lifetime (141 cases). In contrast, no algorithm identified more than 46 (33%) of these cases. Algorithms assessing encounters with both an IE and substance use code had specificities >99% but sensitivities ≤11% with negative predictive values of 83% to 84% and positive predictive values ranging from 75% to 91%. Use of a hepatitis C OR substance use code with an IE-coded encounter resulted in higher sensitivities of 22% to 32% but more false positives and overall positive predictive value of <70%. This algorithm limited to age ≤45yo had the best, but still low, discrimination ability with an area under the receiver operating characteristic curve of 0.62. CONCLUSION: Substance use and hepatitis C codes have poor ability to accurately classify an IE-coded encounter as IDU-IE or routine IE.

Vitreous and Chorioretinal Lesions in People Who Inject Drugs and Are Hospitalized with Bloodstream and Related Infections.

PURPOSE: To determine the prevalence of and to characterize vitreous and chorioretinal lesions, to identify causative organisms, and to correlate symptoms with ophthalmic involvement in people who inject drugs and are hospitalized with bloodstream infection (BSI), related metastatic foci of infection (MFI), or both. DESIGN: An academic hospital-based cross-sectional study. PARTICIPANTS: Patients admitted with BSI or MFI related to injection drug use (IDU). METHODS: Patients underwent a complete eye examination within 72 hours of enrollment. Characteristics including gender; age; race; injection drug of choice (DOC); presence of coinfection with hepatitis B, hepatitis C, or human immunodeficiency virus; pathogen causing systemic infection and type of infection; and history of prior infection related to IDU were recorded. MAIN OUTCOME MEASURES: Presence of vitreous or chorioretinal findings, or both. RESULTS: Ninety-one unique patients with 96 separate hospitalizations for systemic infection were enrolled from March 28, 2018, through March 30, 2020. Vitreous or chorioretinal involvement was identified in 16 of 96 patients (16.7%). The most common ocular findings were intraretinal or white-centered hemorrhage in 9 of 96 patients, chorioretinal infiltrate in 8 of 96 patients, endophthalmitis in 5 of 96 patients, and cotton wool spots in 3 of 96 patients. Of the patients with ocular involvement, only 7 of 16 patients (44%) were symptomatic, and 5 of these were patients with endophthalmitis; the others showed chorioretinal infiltrates or intraretinal or white-centered hemorrhage and cotton wool spots. Staphylococcus aureus was the most common causative pathogen in patients with and without ocular findings. Presence of ocular symptoms, worse visual acuity, and injection DOC of methamphetamine were correlated with the presence of ocular findings. CONCLUSIONS: Patients without ocular symptoms with systemic infections related to IDU may have chorioretinal findings. Further study is needed to characterize better the epidemiologic features of these infections and to identify risk factors for ocular involvement in people who inject drugs.

Inconsistency in Brain Death Determination Should Not Be Tolerated.

Since it was proposed in 1980, the Uniform Determination of Death Act has provided the legal basis for determination of death by neurological criteria. The act contains language that allows for acceptable medical standards to be used to determine death. Since 1995, the American Academy of Neurology has provided guidelines for brain death determination (revised in 2010), but nationwide adherence to these guidelines has been incomplete. This variability could lead to misdiagnosis and erosion of public trust in this important medical practice. Physicians must work together as a profession to push for uniformity and accuracy in death diagnosis.

Secondary syphilis mimicking sarcoidosis.

Secondary syphilis may mimic sarcoidosis due to atypical clinical and pathological presentations. Differential diagnosis of these two is critical since the clinical courses and treatments are different. Highly clinical suspicion and utilization of confirmatory tests in high-risk patients are the key for the differential diagnosis.

Infective Endocarditis Guidelines: The Challenges of Adherence-A Survey of Infectious Diseases Clinicians.

BACKGROUND: Guidelines exist to aid clinicians in managing patients with infective endocarditis (IE), but the degree of adherence with guidelines by Infectious Disease (ID) physicians is largely unknown. METHODS: An electronic survey assessing adherence with selected IE guidelines was emailed to 1409 adult ID physician members of the Infectious Diseases Society of America's Emerging Infections Network. RESULTS: Five hundred fifty-seven physicians who managed IE responded. Twenty percent indicated that ID was not consulted on every case of IE at their hospitals, and 13% did not recommend transthoracic echocardiography (TTE) for all IE cases. The duration of antimicrobial therapy was timed from the first day of negative blood cultures by 91% of respondents. Thirty-four percent of clinicians did not utilize an aminoglycoside for staphylococcal prosthetic valve IE (PVE). Double ß-lactam therapy was "usually" or "almost always" employed by 83% of respondents for enterococcal IE. For patients with active IE who underwent valve replacement and manifested positive surgical cultures, 6 weeks of postoperative antibiotics was recommended by 86% of clinicians. CONCLUSIONS: The finding that adherence was <90% with core guideline recommendations that all patients with suspected IE be seen by ID and that all patients undergo TTE is noteworthy. Aminoglycoside therapy of IE appears to be declining, with double ß-lactam regimens emerging as the preferred treatment for enterococcal IE. The duration of postoperative antimicrobial therapy for patients undergoing valve replacement during acute IE is poorly defined and represents an area for which additional evidence is needed.

Repeat Infective Endocarditis in Persons Who Inject Drugs: "Take Another Little Piece of my Heart".

BACKGROUND: Injection drug use (IDU) is a major risk factor for infective endocarditis (IE). Few data exist on repeat IE (rIE) in persons who inject drugs (PWID). METHODS: Patients ≥18 years old seen at Wake Forest Baptist Medical Center from 2004 to 2017 who met Duke criteria for IE and who self-reported IDU in the 3 months before admission were identified. The subset of PWID who developed rIE, defined as another episode of IE at least 10 weeks after diagnosis of the first episode, was then reviewed. RESULTS: Of the 87 PWID who survived their first episode of IE, 22 (25.3%) experienced rIE and 77.3% had rIE within a year of the first episode. All patients who experienced rIE resumed IDU between episodes of IE. Of the patients with rIE, 54.5% had an infection caused by S. aureus and 22.7% required surgical intervention. Mortality at 1 year was 36.3%. Compared with their first IE episode, patients with rIE had fewer S. aureus infections (P = .01). Compared with PWID who experienced single-episode IE, intravenous prescription opioid use (P = .01), surgery (P < .01), tricuspid valve involvement (P = .02), and polymicrobial infection (P = .03) occurred more often during first episodes of IE in individuals who then developed rIE. CONCLUSIONS: rIE is common among IDU-related IE and confers a high 1-year mortality rate. The microbiology of rIE is varied, with S. aureus being less frequently isolated. More studies on modification of social and clinical risk factors are needed to prevent rIE.

Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations.

BACKGROUND: Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia. METHODS: We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy. CONCLUSIONS: Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.

SINEs, evolution and genome structure in the opossum.

Short INterspersed Elements (SINEs) are non-autonomous retrotransposons, usually between 100 and 500 base pairs (bp) in length, which are ubiquitous components of eukaryotic genomes. Their activity, distribution, and evolution can be highly informative on genomic structure and evolutionary processes. To determine recent activity, we amplified more than one hundred SINE1 loci in a panel of 43 M. domestica individuals derived from five diverse geographic locations. The SINE1 family has expanded recently enough that many loci were polymorphic, and the SINE1 insertion-based genetic distances among populations reflected geographic distance. Genome-wide comparisons of SINE1 densities and GC content revealed that high SINE1 density is associated with high GC content in a few long and many short spans. Young SINE1s, whether fixed or polymorphic, showed an unbiased GC content preference for insertion, indicating that the GC preference accumulates over long time periods, possibly in periodic bursts. SINE1 evolution is thus broadly similar to human Alu evolution, although it has an independent origin. High GC content adjacent to SINE1s is strongly correlated with bias towards higher AT to GC substitutions and lower GC to AT substitutions. This is consistent with biased gene conversion, and also indicates that like chickens, but unlike eutherian mammals, GC content heterogeneity (isochore structure) is reinforced by substitution processes in the M. domestica genome. Nevertheless, both high and low GC content regions are apparently headed towards lower GC content equilibria, possibly due to a relative shift to lower recombination rates in the recent Monodelphis ancestral lineage. Like eutherians, metatherian (marsupial) mammals have evolved high CpG substitution rates, but this is apparently a convergence in process rather than a shared ancestral state.