Characterization and Investigation of Risk Factors for Late-Relapsing Hepatitis After Yellow Fever.

BACKGROUND: Late-relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF is marked by a rebound in liver enzymes and nonspecific clinical manifestations around 46-60 days after YF symptom onset. METHODS: Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017-2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais and were followed up at 30, 45, and 60 days post-symptom onset. RESULTS: From 46 to 60 days post-symptom onset, 16% of YF patients (n = 36/221) exhibited a rebound of aminotransferases (aspartate aminotransferase or alanine aminotransferase >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF. CONCLUSIONS: These findings provide new data on the clinical course of Late-relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF.

Comprehensive Improvement of Cardiology Inpatient Transfers: A Bed-availability Triggered Approach.

Introduction: Patient transfers pose a potential risk during hospitalizations. Structured communication practices are necessary to ensure effective handoffs, but occur amidst competing priorities and constraints. We sought to design and implement a multidisciplinary process to enhance communication between pediatric cardiovascular intensive care unit and cardiology floor teams with a comprehensive approach evaluating efficiency, safety, and culture. Methods: We conducted a prospective quality improvement study to enact a bed-availability triggered bedside handoff process. The primary aim was to reduce the time between handoff and unit transfer. Secondary metrics captured the impact on safety (reported safety events, overnight transfers, bounce backs, and I-PASS utilization), efficiency (transfer latency, unnecessary patient handoffs, and cumulative time providers were engaged in handoffs), and culture (team members perceptions of satisfaction, collaboration, and handoff efficiency via survey data). Results: Eighty-two preimplementation surveys, 26 stakeholder interviews, and 95 transfers were completed during the preintervention period. During the postintervention period, 145 handoffs were audited. We observed significant reductions in transfer latency, unnecessary handoffs, and cumulative provider handoff time. Overnight transfers decreased, and no negative impact was observed in reported safety events or bouncebacks. Survey results showed a positive impact on collaboration, efficiency, and satisfaction among team members. Conclusions: Developing safer handoff practices require a collaborative, structured, and stepwise approach. Advances are attainable in high-volume centers, and comprehensive measurement of change is necessary to ensure a positive impact on the overall patient and provider environment.

Virtual Communication Embedded Bedside ICU Rounds: A Hybrid Rounds Practice Adapted to the Coronavirus Pandemic.

OBJECTIVES: Coronavirus disease 2019 containment strategies created challenges with patient-centered ICU rounds. We examined how hybrid rounds with virtual communication added to in-person rounds could facilitate social distancing while maintaining patient-centered care. DESIGN: Continuous quality improvement. SETTING: Quaternary care referral pediatric hospital. PATIENTS: Daytime rounds conducted on PICU patients. INTERVENTIONS: Following a needs assessment survey and pilot trials, multiple technological solutions were implemented in a series of plan-do-study-act cycles. Hybrid rounds model was deployed where a videoconference platform was used to establish communication between the bedside personnel (nurse, patient/family, and partial ICU team) with remotely located remaining ICU team, ancillary, and consultant providers. Floor labels marking 6-feet distance were placed for rounders. MEASUREMENTS AND MAIN RESULTS: Outcome metrics included compliance with social distancing, mixed methods analysis of surveys, direct interviews of providers and families, and reports of safety concerns. The clinicians adopted hybrid rounds readily. Compliance with social distancing and use of floor labels needed reminders. One-hundred fourteen providers completed the feedback survey. Twenty-five providers and 11 families were interviewed. Feedback about hybrid rounds included inability to teach effectively, suboptimal audio-video quality, loss of situational awareness of patient/unit acuity, alarm interference, and inability to socially distance during other ICU interactions. Benefits noted were improved ancillary input, fewer interruptions, improved efficiency, opportunity to integrate with data platforms, and engage remote consultants and families. Nurses and families appreciated the efforts to ensure safety but wanted the ICU attending/fellow supervising the team to participate at bedside, during rounds. Clinicians appreciated the multidisciplinary input but felt that teaching was difficult. CONCLUSIONS: Hybrid rounds employed during pandemic facilitated social distancing while retaining patient-centered multidisciplinary ICU rounds but compromised teaching during rounds. A change to ingrained rounding habits needs team commitment and ongoing optimization. The hybrid rounds model has potential for generalizability to other settings.

T-cell activation profiles distinguish hemophagocytic lymphohistiocytosis and early sepsis.

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disorder of immune hyperactivation that has been described as a cytokine storm. Sepsis due to known or suspected infection has also been viewed as a cytokine storm. Although clinical similarities between these syndromes suggest similar immunopathology and may create diagnostic uncertainty, distinguishing them is critical as treatments are widely divergent. We examined T-cell profiles from children with either HLH or sepsis and found that HLH is characterized by acute T-cell activation, in clear contrast to sepsis. Activated T cells in patients with HLH were characterized as CD38high/HLA-DR+ effector cells, with activation of CD8+ T cells being most pronounced. Activated T cells were type 1 polarized, proliferative, and displayed evidence of recent and persistent activation. Circulating activated T cells appeared to be broadly characteristic of HLH, as they were seen in children with and without genetic lesions or identifiable infections and resolved with conventional treatment of HLH. Furthermore, we observed even greater activation and type 1 polarization in tissue-infiltrating T cells, described here for the first time in a series of patients with HLH. Finally, we observed that a threshold of >7% CD38high/HLA-DR+ cells among CD8+ T cells had strong positive and negative predictive value for distinguishing HLH from early sepsis or healthy controls. We conclude that the cytokine storm of HLH is marked by distinctive T-cell activation whereas early sepsis is not, and that these 2 syndromes can be readily distinguished by T-cell phenotypes.

Outcomes among patients with infantile spasms treated with hormonal therapy and adjuvant topiramate versus hormonal therapy alone.

Hormonal therapy is the first-line treatment for infantile spasms and is sometimes used in combination with topiramate for better seizure control and potentially improved developmental outcomes. Retrospective review of pediatric patients with infantile spasms, with data compiled on patient sex, age at onset, etiology, electroencephalographic and imaging findings, topiramate use, spasm resolution (at one, six, and 12 months), and developmental outcome (at 12 months). Of 105 patients screened, 55 (28 female) met inclusion criteria (28 [51%] had spasms with known etiology and 27 [49%] had spasms with unknown etiology). Forty-six patients were followed for 12 months or longer to determine seizure outcome; a 12-month developmental assessment was documented for 49 patients. Thirty-seven patients (67%) received combination therapy; 18 (33%) received hormonal therapy alone. Resolution of spasms was comparable among treatment groups, with no difference relative to spasm etiology (p>0.18 for all). No difference was found in developmental outcomes with and without adjunct topiramate (p=0.38). Combination therapy was the most common treatment at our institution. However, combination therapy was not found to be beneficial for the treatment of spasms or developmental outcomes when compared to hormonal therapy alone.

Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis.

The HLH-2004 criteria are used to diagnose hemophagocytic lymphohistiocytosis (HLH), yet concern exists for their misapplication, resulting in suboptimal treatment of some patients. We sought to define the genomic spectrum and associated outcomes of a diverse cohort of children who met the HLH-2004 criteria. Genetic testing was performed clinically or through research-based whole-exome sequencing. Clinical metrics were analyzed with respect to genomic results. Of 122 subjects enrolled over the course of 17 years, 101 subjects received genetic testing. Biallelic familial HLH (fHLH) gene defects were identified in only 19 (19%) and correlated with presentation at younger than 1 year of age (P < .0001). Digenic fHLH variants were observed but lacked statistical support for disease association. In 28 (58%) of 48 subjects, research whole-exome sequencing analyses successfully identified likely molecular explanations, including underlying primary immunodeficiency diseases, dysregulated immune activation and proliferation disorders, and potentially novel genetic conditions. Two-thirds of patients identified by the HLH-2004 criteria had underlying etiologies for HLH, including genetic defects, autoimmunity, and malignancy. Overall survival was 45%, and increased mortality correlated with HLH triggered by infection or malignancy (P < .05). Differences in survival did not correlate with genetic profile or extent of therapy. HLH should be conceptualized as a phenotype of critical illness characterized by toxic activation of immune cells from different underlying mechanisms. In most patients with HLH, targeted sequencing of fHLH genes remains insufficient for identifying pathogenic mechanisms. Whole-exome sequencing, however, may identify specific therapeutic opportunities and affect hematopoietic stem cell transplantation options for these patients.

Pathogenic potential of environmental resident fungi from ornithogenic soils of Antarctica.

We assessed the diversity of cultivable fungi in the ornithogenic soil nests of bird species like Phalacrocorax atriceps, Macronectes giganteus, Pygoscelis antarcticus, and Pygoscelis papua in the Antarctic islands. From 481 fungi isolated at 15 °C, only 50 displayed growth at 37 °C, and were identified as 14 species of 15 genera. Aspergillus fumigatus, Penicillium chrysogenum, and Rhodotorula mucilaginosa were the most abundant species obtained. Fifty taxa grew at 40 °C; displayed haemolytic and phospholipase activities; produced tiny spores, capsule, and melanin; showed growth at different pH; and showed resistance to amphotericin B. Interestingly, the minimum inhibitory concentration of amphotericin B increased by 5-10 fold for some A. fumigatus isolates after phagocytosis by amoeba. Our results show relations among fungal community compositions present in Antarctic ornithogenic soil and their pathogenic risk to humans in vitro. As the Antarctica Peninsula is a major region of the planet affected by global climate changes, our results, though preliminary, raise concerns about the dispersal of potential pathogenic microbes present in Antarctic substrates by wild birds, which can fly great distances and spread potential pathogens mainly to South America and Oceania.

Reduction in hospitalisations and emergency department visits for frail patients with heart failure: Results of the UMIPIC healthcare programme.

OBJECTIVES: Heart failure (HF) is a disease with high morbidity and mortality. We evaluated the usefulness of the Comprehensive Management Units for Patients with HF (Unidades de Manejo Integral para Pacientes con IC [UMIPIC]) programme. PATIENTS AND METHOD: We analysed the patient data from the UMIPIC programme, which was recorded in the HF registry (RICA) of the Spanish Society of Internal Medicine. We compared emergency department visits and hospitalisations for any cause and for HF during the year prior to inclusion in the programme against those that occurred during the subsequent follow-up year, using the chi-squared test. RESULTS: A total of 258 patients (mean age, 80years; 51.9% women) were included in the study. During the previous year, there were 693 hospitalisations for all causes and 174 hospitalisations during the follow-up (75% reduction, P<.001). There were 613 hospitalisations for HF during the previous year and 92 during the follow-up (85% reduction, P<.001); 655 vs. 302 in terms of emergency department visits for any cause (53.9% reduction, P<.001); and 440 vs. 120 for emergency department visits for HF (72% reduction, P<.001). There were no significant differences in the number of hospitalisations or emergency department visits for causes other than HF. CONCLUSIONS: The UMIPIC programme based on the comprehensive care of elderly patients with HF and comorbidity reduces the rate of hospital readmissions and emergency department visits during the first year of follow-up.

Grammatical constraints on phonological encoding in speech production.

To better understand the influence of grammatical encoding on the retrieval and encoding of phonological word-form information during speech production, we examine how grammatical class constraints influence the activation of phonological neighbors (words phonologically related to the target--e.g., MOON, TWO for target TUNE). Specifically, we compare how neighbors that share a target's grammatical category (here, nouns) influence its planning and retrieval, assessed by picture naming latencies, and phonetic encoding, assessed by word productions in picture names, when grammatical constraints are strong (in sentence contexts) versus weak (bare naming). Within-category (noun) neighbors influenced planning time and phonetic encoding more strongly in sentence contexts. This suggests that grammatical encoding constrains phonological processing; the influence of phonological neighbors is grammatically dependent. Moreover, effects on planning times could not fully account for phonetic effects, suggesting that phonological interaction affects articulation after speech onset. These results support production theories integrating grammatical, phonological, and phonetic processes.

Synthesis and evaluation of the antiparasitic activity of bis-(arylmethylidene) cycloalkanones.

A series of bis-(arylmethylidene)-cycloalkanones was synthesized by cross-aldol condensation. The activity of the compounds was evaluated against amastigotes forms of Trypanosoma cruzi and promastigotes forms of Leishmania amazonensis. The cytotoxicity of the active compounds on uninfected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their antiparasitic effects. Six compounds displayed trypanocidal activity against amastigotes intracellular forms of T. cruzi with IC50 values ranging from 7.0 to 249 µM. Besides these six compounds, eight other molecules exhibited significant leishmanicidal activity (IC50 values ranging from 0.6 to 110.4 µM). Two compounds can be considered as promising antiparasitic lead molecules because they showed IC50 values in the low-micromolar range (≤1.2 µM) with an adequate SI (≥19.9). To understand the mechanism of action of these compounds, two possible molecular targets were investigated: trypanothione reductase (TR) and cruzain.

The Computer Book of the Internal Medicine Resident: competence acquisition and achievement of learning objectives.

BACKGROUND: The Computer Book of the Internal Medicine resident (CBIMR) is a computer program that was validated to analyze the acquisition of competences in teams of Internal Medicine residents. OBJECTIVES: To analyze the characteristics of the rotations during the Internal Medicine residency and to identify the variables associated with the acquisition of clinical and communication skills, the achievement of learning objectives and resident satisfaction. METHODS: All residents of our service (n=20) participated in the study during a period of 40 months. The CBIMR consisted of 22 self-assessment questionnaires specific for each rotation, with items on services (clinical workload, disease protocolization, resident responsibilities, learning environment, service organization and teamwork) and items on educational outcomes (acquisition of clinical and communication skills, achievement of learning objectives, overall satisfaction). Associations between services features and learning outcomes were analyzed using bivariate and multivariate analysis. RESULTS: An intense clinical workload, high resident responsibilities and disease protocolization were associated with the acquisition of clinical skills. High clinical competence and teamwork were both associated with better communication skills. Finally, an adequate learning environment was associated with increased clinical competence, the achievement of educational goals and resident satisfaction. CONCLUSIONS: Potentially modifiable variables related with the operation of clinical services had a significant impact on the acquisition of clinical and communication skills, the achievement of educational goals, and resident satisfaction during the specialized training in Internal Medicine.

[The Computer Book of the Internal Medicine resident: validity and reliability of a questionnaire for self-assessment of competences in internal medicine residents]. / El Libro Informático del residente de Medicina Interna: validez y fiabilidad de un cuestionario para la autoevalución de competencias en residentes de Medicina Interna.

BACKGROUND: There are no simple and validated instruments for evaluating the training of specialists. OBJECTIVES: To analyze the reliability and validity of a computerized self-assessment method to quantify the acquisition of medical competences during the Internal Medicine residency program. METHODS: All residents of our department participated in the study during a period of 28 months. Twenty-two questionnaires specific for each rotation (the Computer-Book of the Internal Medicine Resident) were constructed with items (questions) corresponding to three competence domains: clinical skills competence, communication skills and teamwork. Reliability was analyzed by measuring the internal consistency of items in each competence domain using Cronbach's alpha index. Validation was performed by comparing mean scores in each competence domain between senior and junior residents. Cut-off levels of competence scores were established in order to identify the strengths and weaknesses of our training program. Finally, self-assessment values were correlated with the evaluations of the medical staff. RESULTS: There was a high internal consistency of the items of clinical skills competences, communication skills and teamwork. Higher scores of clinical skills competence and communication skills, but not in those of teamwork were observed in senior residents than in junior residents. The Computer-Book of the Internal Medicine Resident identified the strengths and weaknesses of our training program. We did not observe any correlation between the results of the self- evaluations and the evaluations made by staff physicians. CONCLUSIONS: The items of Computer-Book of the Internal Medicine Resident showed high internal consistency and made it possible to measure the acquisition of medical competences in a team of Internal Medicine residents. This self-assessment method should be complemented with other evaluation methods in order to assess the acquisition of medical competences by an individual resident.

The role of plasmapheresis in critical illness.

In this article, the authors review the current recommendations from the American Society for Apheresis regarding the use of plasmapheresis in many of the diseases that intensivists commonly encounter in critically ill patients. Recent experience indicates that therapeutic plasma exchange may be useful in a wide spectrum of illnesses characterized by microvascular thrombosis, the presence of autoantibodies, immune activation with dysregulation of immune response, and some infections.

Synergy against drug-resistant HIV-1 with the microbicide antiretrovirals, dapivirine and tenofovir, in combination.

OBJECTIVE: To evaluate the candidate antiretroviral microbicide compounds, dapivirine (DAP) and tenofovir (TFV), alone and in combination against the transmission of wild-type and nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 from different subtypes. DESIGN AND METHODS: We determined single-drug efficacy of the RTIs, DAP and TFV, against subtype B and non-B wild-type and NNRTI-resistant HIV-1 in vitro. To assess breadth of activity, compounds were tested alone and in combination against wild-type and NNRTI-resistant subtype C primary HIV-1 isolates and complimentary clonal HIV-1 from subtypes B, C and CRF02_AG to control for viral variation. Early infection was quantified by counting light units emitted from TZM-bl cells less than 48-h postinfection. Combination ratios were based on drug inhibitory concentrations (IC(50)s) and combined effects were determined by calculating combination indices. RESULTS: Both candidate microbicide antiretrovirals demonstrated potent anti-NNRTI-resistant HIV-1 activity in vitro, albeit the combination protected better than the single-drug treatments. Of particular interest, the DAP with TFV combination exhibited synergy (50% combination index, CI(50) = 0.567) against subtype C NNRTI-resistant HIV-1, whereas additivity (CI(50) = 0.987) was observed against the wild-type counterpart from the same patient. The effect was not compounded by the presence of subdominant viral fractions, as experiments using complimentary clonal subtype C wild-type (CI(50) = 0.968) and NNRTI-resistant (CI(50) = 0.672) HIV-1, in lieu of the patient quasispecies, gave similar results. CONCLUSION: This study supports the notion that antiretroviral drug combinations may retain antiviral activity against some drug-resistant HIV-1 despite subtype classification and quasispecies diversity.

Analysis of temporal artery biopsies in an 18-year period at a community hospital.

OBJECTIVE: To identify analytical and clinical variables that may improve the effectiveness of temporal artery biopsy (TAB) for the diagnosis of giant cell arteritis (GCA). MATERIALS AND METHODS: A retrospective study of TABs conducted between 1989 and 2007 at the 450-bed Hospital Parc Taulí, Sabadell. Demographic data, clinical manifestations, analytical data prior to the biopsy and final diagnoses were recorded, including only those cases in which these data were reflected in the clinical history. RESULTS: In this period, 278 TABs were conducted in 181 women (65.1%) and 97 men (mean age 74 years). Seventy-nine (28.4%) were positive (GCA+) and 199 (71.5%) negative (TAB-). The most frequent final diagnoses in the TAB- group were: polymyalgia rheumatica (PMR) (18.6%), giant cell arteritis plus negative TAB (GCA-) (13.6%), tension headache (7.5%), infection (7.5%), other vasculitis (7.5%), and neoplasm (6.0%). The GCA+ group was compared with the TAB- group, the GCA- group and the PMR group. In the multivariate analysis only headache (RR 3.6), jaw claudication (RR 2.9) and abnormal temporal artery on palpation (RR 2.5) revealed statistical differences between the GCA+ and TAB- groups. CONCLUSION: One third of the biopsies performed at our centre were positive for GCA. The clinical variables that best predicted a positive TAB in our series were headache, jaw claudication, and abnormal temporal artery on palpation.

Investigating the mechanisms of hoarding from an experimental perspective.

BACKGROUND: Acquiring and discarding objects are routine decision processes for most people. Despite the ubiquitous need to make such decisions, little is known about how they are made and what goes wrong when individuals acquire and fail to discard so many items that many areas of their home become unlivable (i.e., clinical hoarding). We hypothesize that clinical hoarding reflects a normal variation in the tendency to acquire and retain objects, only just at a more extreme level. METHODS: To test this hypothesis, we examined 89 nonclinical, undergraduate students' performance on a novel experimental paradigm that measures decisions about acquiring and discarding everyday objects. To test our hypothesis, and validate our task as a possible research tool for studying hoarding, we related decisions on the task to a variety of measures known to correlate with clinical hoarding. The paradigm was sensitive to individual differences, as subjects varied widely in the quantity of objects they chose to acquire and retain under an increasing pressure to discard. In addition, we replicated expected relationships from the clinical hoarding literature between acquisition and retention tendencies and self-report measures of hoarding, indecisiveness, and obsessive-compulsive behavior. RESULTS: Our data suggest that decisions about objects, even in a nonclinical undergraduate population, vary widely and are influenced by the same variables that influence clinical hoarding, but to a less extreme degree. CONCLUSIONS: Future research with this experimental task can separately investigate the role of acquisition, retention, impulsivity, and sensitivity to constraints in clinical hoarding to inform our understanding of this disorder.

Obsessive-compulsive disorder among African Americans and blacks of Caribbean descent: results from the National Survey of American Life.

BACKGROUND: There is limited research regarding the nature and prevalence of obsessive-compulsive disorder (OCD) among various racial and ethnic subpopulations within the United States, including African Americans and blacks of Caribbean descent. Although heterogeneity within the black population in the United States has largely been ignored, notable differences exist between blacks of Caribbean descent and African Americans with respect to ethnicity, national heritage, and living circumstances. This is the first comprehensive examination of OCD among African Americans and blacks of Caribbean descent. METHODS: Data from the National Survey of American Life, a national household probability sample of African Americans and Caribbean blacks in the United States, were used to examine rates of OCD among these groups. RESULTS: Lifetime and 12-month OCD prevalence estimates were very similar for African Americans and Caribbean blacks. Persistence of OCD and rates of co-occurring psychiatric disorders were very high and also similar between African American and Caribbean black respondents. Both groups had high levels of overall mental illness severity and functional impairment. Use of services was low for both groups, particularly in specialty mental health settings. Use of anti-obsessional medications was also rare, especially among the Caribbean black OCD population. CONCLUSIONS: OCD among African Americans and Caribbean blacks is very persistent, often accompanied by other psychiatric disorders, and is associated with high overall mental illness severity and functional impairment. It is also likely that very few blacks in the United States with OCD are receiving evidence-based treatment and thus considerable effort is needed to bring treatment to these groups.