bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutaneous drug hypersensitivity: developments and controversies
Authors: Brockow Knut , Pfützner Wolfgang 
Published: May 2019

Purpose of reviewCutaneous drug hypersensitivity reactions (CDHRs) are a complicated area with multiple clinical manifestations and differential diagnoses, requiring differentiated diagnostic measurements and optimized therapeutic management.Recent findingsDisseminated CDHRs to classical drugs can be classified by a simple algorithm, whereas chemotherapeuticals or biopharmaceuticals may show drug-specific and atypical clinical presentations. Controversies in drug hypersensitivity diagnosis exist about the benefit and accuracy of in-vitro tests. Although skin tests are the best means of detecting sensitization to drugs, methods have not been sufficiently standardized. The necessity for skin tests before performing drug provocation test (DPT) and of prolonged DPTs is discussed in selected patients. If a suspicion has been documented, β-lactam allergy should be excluded. The standard allergy diagnosis is done by an allergist. In case of urgent need because of an infection and low risk according to history, faster delabeling pathways have been developed. There is weak evidence that patients with mastocytosis may have a slightly increased risk of developing immediate-type drug hypersensitivity; however, if considerations are taken, drugs do not have to be withheld for this patient group. There is particular need for improved diagnostic measurements in patients with drug-induced severe cutaneous adverse reactions (SCARs), both identifying the offending drug and detecting individuals at risk. Further challenges encompass appropriate treatments during the acute as well as chronic phase of SCARs.SummaryRecent literature has contributed to our understanding of clinical manifestations and existing controversies and future needs in this area.
Building Provider–Caregiver Partnerships: Curricula for Medical Students and Residents
Authors: Blackie Michael , Baughman Kristin R. , Palmisano Barbara , Sanders Margaret , Sperling David , Scott Erin , Radwany Steven , Drost Jennifer , Thomas Jon 
Published: May 2019

Problem
A disconnect exists between caregivers and health care providers, resulting in fragmented communication, which increases caregiver stress and compromises patient care. Although providers have a responsibility to recognize caregiver burden, they receive scant training on issues important to caregivers.

Approach
From 2014 to 2017, as part of the Building Caregiver Partnerships Through Interprofessional Education project—a collaborative effort between Northeast Ohio Medical University and Summa Health—the authors developed curricula to foster effective partnerships between health care providers and caregivers by exposing medical students and residents to highly personal caregiving narratives. The curricula center on a short film featuring 4 families representing diverse caregiving experiences. The authors crafted several discussion guides, case-based learning exercises, structured clinical encounters, team-based simulations, and clinical cases as companion educational tools for the film.

Outcomes
Medical students reported the educational tools piloted to be valuable in broadening their understanding of caregivers’ needs, while residents reported the educational tools piloted to also be valuable in improving their communication and building partnerships with caregivers. Undergraduate and graduate faculty reported finding the pilots valuable.

Next Steps
Future goals include conducting an outcome evaluation, based on ACGME milestones, to identify and examine clinical outcomes to determine whether communication increases and quality of care improves as a result of the project. The authors would also like to include caregivers in the evaluation. Finally, because caregiving is best addressed from a team approach, the authors plan to pilot the project at other health professions programs.
The dark side of Sjögren's syndrome: the possible pathogenic role of infections
Authors: Bartoloni Elena , Alunno Alessia , Gerli Roberto 
Published: May 2019

Purpose of review
To highlight recent findings on pathogenic mechanisms and clinical associations which characterize the role of infectious agents as triggers for Sjögren's syndrome development.

Recent findings
Several candidate infectious agents have been identified to induce the autoimmune and inflammatory pathways leading to Sjögren's syndrome clinical appearance in the setting of a genetic background. This is reinforced by the demonstration that Sjögren's syndrome patients are characterized by higher prevalence of seropositivity to virus and bacterial agents in comparison with general population. Moreover, these agents may infect salivary gland epithelial cells. Stronger evidence confirmed the role of some viruses, like Epstein–Barr, as triggers of the disease and different mechanisms have been demonstrated to interplay. Recent experimental and clinical studies supported the adjunctive role of an altered buccal and intestinal microbial composition and chronic inflammatory response to Helicobacter pylori in disease induction. Finally, latent viral infections and immune system chronic stimulation induced by persistent infections may participate in disease lymphoproliferative evolution.

Summary
Different viral and bacterial agents have been identified as triggers in Sjögren's syndrome induction and contributors to the chronic immune system stimulation underlying lymphoproliferative complication. Deeper knowledge of involved microbial agents and pathogenic mechanisms linking Sjögren's syndrome and infections may help the identification of preventive therapeutic strategy.
A Systematic Review and Standardized Comparison of Available Evidence for Outcome Measures Used to Evaluate Proximal Humerus Fracture Patients
Authors: Nowak Lauren L. , Davis Aileen M. , Mamdani Muhammad , Beaton Dorcas , Kennedy Carol , Schemitsch Emil H. 
Published: May 2019

Objectives:
To summarize and appraise any patient-reported or clinician-measured outcome measures based on their measurement properties in proximal humerus fracture patients.

Data Sources and Study Selection:
MEDLINE, EMBASE, and CINAHL were searched from January 2000 to August 2018 to identify all studies of proximal humerus fracture patients that reported a measurement property evaluation of an outcome measure.

Data Extraction and Synthesis:
Quality appraisal of each measure was completed using the Evaluating the Measurement of Patient-Reported Outcomes (EMPRO) tool. The EMPRO takes into account all studies of each measure, and the overall score is transformed linearly to a range of 0 (lowest) to 100 (best).

Results:
Eleven instruments were identified. Intended concepts of the instruments included clinician-measured shoulder function, patient-reported function or disability, and patient-reported general health state. Only the Disabilities of the Arm, Shoulder and Hand (DASH), Oxford Shoulder Score, Constant Score, University of California, Los Angeles Shoulder Score, and EuroQol 5 Dimension (EQ5D) were evaluated in more than 1 study. The Shoulder Function Index (SFINX), DASH, and EQ5D had the highest EMPRO scores (80, 66, and 58, respectively). The SFINX and DASH consistently scored among the top 3 instruments for each attribute.

Conclusions:
Evidence on the measurement properties of outcome measures for proximal humerus fracture patients is limited. With the available evidence, the SFINX is recommended as a clinician-measured functional outcome measure, the DASH as a patient-reported functional outcome measure, and the EQ5D as a general health status measure.
Ligamentous Lisfranc Injury: A Biomechanical Comparison of Dorsal Plate Fixation and Transarticular Screws
Authors: Bansal Ankit , Carlson Daniel A. , Owen John R. , Cheatham Seth A. , Williams D. S. Blaise , Kates Stephen L. , Wayne Jennifer S. 
Published: May 2019

Objectives:
Optimal fixation technique after purely ligamentous Lisfranc injury remains controversial. This biomechanical study compares dorsal plate versus transarticular screw fixation by measuring dorsal and plantar joint diastasis. A unique protocol was developed, using reflective triad markers and positional cameras.

Methods:
Eleven cadaveric matched pairs were assigned to either transarticular screw or dorsal plate fixation. Two reflective triad markers were placed into the medial cuneiform (C1) and second metatarsal base (MT2). Three cameras recorded the 3-dimensional location of triads to quantify C1-MT2 diastasis in the following states: intact Lisfranc ligament (INTACT), cut ligament (CUT), fixed (SCREW or PLATE) joint, and fixed joint after 10,000 loaded cycles. On completion, the plantar Lisfranc ligament insertions were identified, and plantar diastasis was determined using additional reflective triads. Statistical post hoc pairwise comparisons assessed differences in diastasis.

Results:
C1-MT2 diastasis in the CUT state increased relative to INTACT (P < 0.001). SCREW fixation reduced C1-MT2 diastasis relative to CUT at dorsal (P < 0.007) and plantar (P = 0.015) locations after cycling. PLATE fixation significantly reduced dorsal diastasis relative to CUT (P < 0.001) but not for plantar diastasis (P > 0.99). PLATE plantar diastasis was numerically higher than INTACT but not significantly (P > 0.39). PLATE plantar diastasis tended to be greater than SCREW before cycling (P = 0.068) and after cycling (P = 0.080).

Conclusions:
Transection of the Lisfranc ligament complex yielded C1-MT2 diastasis. Both SCREW and PLATE fixation successfully reduced dorsal diastasis. However, upon load, the PLATE resulted in greater plantar diastasis, nearly statistically different relative to the SCREW. Cyclic loading at 343 N did not worsen diastasis.
Degenerative Disc Disease
Authors: Battié Michele C. , Joshi Anand B. , Gibbons Laura E. 
Published: May 2019

Study Design.
A systematic search and review

Objective.
The aim of this study was to investigate the term, degenerative disc disease, to elucidate its current usage and inform clinical, research, and policy recommendations.

Summary of Background Data.

Degenerative disc disease has long been a dominant concept in common, painful spinal disorders. Yet, despite its pervasiveness and important clinical consequences and controversies, there has not been a systematic examination of its use and meaning in the scientific literature.

Methods.
We conducted a systematic search of publications using the term degenerative disc disease from 2007 through 2016 in Ovid MEDLINE (R), Embase, CINAHL, and Scopus. Two investigators independently reviewed all publications in the primary sample. Publication and author identifiers, and qualitative study descriptors were extracted. Finally, the definition of degenerative disc disease was placed in one of eight categories. Data were summarized using descriptive statistics.

Results.

Degenerative disc disease appeared in the titles of 402 publications in the primary sample and increased in frequency by 189% from the first to the last 3 years of the decade. No single definition was used in the majority of publications, and most frequently, the term was used without any definition provided (30.1%). In other cases, degenerative disc disease specifically included radiculopathy or myelopathy (14.4%), or only back or neck pain (5.5%), or was equated with disc degeneration regardless of the presence of symptoms (15.4%), or with discogenic pain or disc degeneration as a presumed cause of axial pain (12.7%). Another 7.2% comprised a mix of broad ranging findings and diagnoses. The most notable differences in definitions occurred between surgeons and other disciplines, and when applied to cervical versus lumbar regions.

Conclusion.
Despite longstanding use and important consequences, degenerative disc disease represents an underdeveloped concept, with greatly varying, disparate definitions documented. Such inconsistencies challenge clear, accurate communication in medicine and science, create confusion and misconceptions among clinicians, patients and others, and hinder the advancement of related knowledge.

Level of Evidence: 4
Typologies of Decision-Makers in the ICU: A Qualitative Study of Patients With Acute Respiratory Distress Syndrome and Sepsis and Their Surrogates
Authors: Lava Michael S. , Dickert Neal W. , Frew Paula M. , Martin Gregory S. , Sevransky Jonathan E. 
Published: May 2019

Objectives:
To develop hypotheses of patient and surrogate’s rationale for decision-making.

Design:
We pursued a qualitative study of patients with acute respiratory distress syndrome or sepsis and their surrogates. Fourteen patients and 28 surrogates were given semistructured interviews while in the ICU and again 30 days later. The interviews focused on goal outcomes for the ICU stay and why a patient or surrogate would want a specific intervention (e.g., intubation and cardiopulmonary resuscitation).

Setting:
ICU of tertiary care academic hospital.

Patients:
Fourteen acute respiratory distress syndrome or sepsis patients and 28 of their surrogates.

Interventions:
None.

Measurements and Main Results:
Interviews were analyzed using grounded theory and the constant comparative method on NVivo 10.0 (QSR International, Melbourne, Australia). We identified the following four typologies of decision-making rationale: 1) “Timers”—determined decisions based on the length of time on life support; 2) “Natural Livers”—rejected interventions using a “machine”; 3) “Deferrers”—relied on physician for decision-making and prognosis; and 4) “Believers”—relied on a higher power for guidance.

Conclusions:
Our hypothesized typologies need validation in a prospective observational trial. If validated, they may allow for better clinician communication.
Thrombomodulin, Plasminogen Activator Inhibitor-1 and Protein C Levels, and Organ Dysfunction in Sepsis
Authors: Katayama Shinshu , Koyama Kansuke , Shima Jun , Tonai Ken , Goto Yuya , Koinuma Toshitaka , Nunomiya Shin 
Published: May 2019

Objectives:
Since endothelial function is closely related to organ dysfunction in sepsis and the relationship among endothelial injury, organ dysfunction, and other biomarkers remains unclear, we aimed to evaluate the correlation among endothelial injury, organ dysfunction, and several biomarkers in patients with sepsis.

Design:
This was a retrospective observational study.

Setting:
The study was conducted in a university hospital with 14 mixed ICU beds.

Patients:
ICU patients with sepsis from June 2011 to December 2017 were enrolled in this study.

Interventions:
Endothelial biomarkers (soluble thrombomodulin, plasminogen activator inhibitor-1, and protein C) and markers of inflammation and coagulation were evaluated during the ICU stay. Sequential Organ Failure Assessment scores were assessed for 7 days after ICU admission to determine organ dysfunction. Variables were compared among five stratified groups according to the Sequential Organ Failure Assessment score (0–2, 3–5, 6–8, 9–12, and 13–24). Regression analysis and 95% CIs were used to evaluate trends in biomarkers.

Measurements and Main Results:
The patients were divided into five stratified groups (Sequential Organ Failure Assessment 0–2, n = 159 [20.5%]; Sequential Organ Failure Assessment 3–5, n = 296 [38.2%]; Sequential Organ Failure Assessment 6–8, n = 182 [23.5%]; Sequential Organ Failure Assessment 9–12, n = 75 [9.7%]; Sequential Organ Failure Assessment 13–24, n = 31 [4.0%]). Protein C activity was significantly correlated with the severity of organ dysfunction. It was lower on day 1, increased upon successful treatment, and was significantly higher in groups with lower Sequential Organ Failure Assessment scores.

Conclusions:
Trends and activity of protein C were superior in predicting organ dysfunction compared with other endothelial biomarkers. Monitoring the level of protein C activity is an ideal tool to monitor organ dysfunctions in patients with sepsis.
Low ICU Burnout in a Safety Net Hospital
Authors: LeClaire Michele M. , Poplau Sara , Prasad Kriti , Audi Crystal , Freese Rebecca , Linzer Mark 
Published: May 2019

Objectives:
Burnout tends to be high in ICU settings. Stressors include serious patient illness, round-the-clock acute events, and end-of-life (nonbeneficial) care. We report on an ICU with very low burnout scores. We sought to understand factors that might be responsible for these favorable outcomes.

Design:
We compared ICU scores on burnout and its predictors with scores in non-ICU providers, merging scores in four ICUs (burn, medical, surgical, and pediatrics). Analyses included descriptive statistics, as well as general estimating equations to assess odds of burnout in ICU clinicians versus non-ICU clinicians.

Setting:
Annual wellness survey performed in October 2017 at Hennepin Healthcare System, an integrated system of care that includes an urban safety net hospital in Minneapolis, MN.

Subjects:
Six-hundred seventy-nine providers (physicians and advanced practice providers).

Interventions:
None.

Measurements and Main Results:
Annual surveys are performed using the validated Mini-Z 10 item wellness instrument. The Mini-Z assesses stress, satisfaction, and burnout, as well as known predictors including work control, chaos, teamwork, values alignment, and electronic medical record-related stress. Response rate in ICUs was 70% (64% elsewhere). Ten percentage of ICU clinicians reported burnout versus 37% of other providers (p = 0.015). ICUs were characterized as having lower chaos, less stress, and very high teamwork and values alignment between clinicians and leaders. Odds of burnout were four times lower in ICU clinicians (odds ratio, 0.24; 95% CI, 0.06–0.96; p = 0.043). Of all Hennepin Healthcare System providers, those with values not aligned with leaders had 3.28 times the odds of burnout (95% CI, 1.92–5.59; p < 0.001).

Conclusions:
Low burnout can be present in a busy, safety net ICU. Explicitly aligning values between clinicians and leaders may hold promise as a remediable worklife factor for producing these favorable results.
Clinician Perception of a Machine Learning–Based Early Warning System Designed to Predict Severe Sepsis and Septic Shock*
Authors: Ginestra Jennifer C. , Giannini Heather M. , Schweickert William D. , Meadows Laurie , Lynch Michael J. , Pavan Kimberly , Chivers Corey J. , Draugelis Michael , Donnelly Patrick J. , Fuchs Barry D. , Umscheid Craig A. 
Published: May 2019

Objective:
To assess clinician perceptions of a machine learning–based early warning system to predict severe sepsis and septic shock (Early Warning System 2.0).

Design:
Prospective observational study.

Setting:
Tertiary teaching hospital in Philadelphia, PA.

Patients:
Non-ICU admissions November–December 2016.

Interventions:
During a 6-week study period conducted 5 months after Early Warning System 2.0 alert implementation, nurses and providers were surveyed twice about their perceptions of the alert’s helpfulness and impact on care, first within 6 hours of the alert, and again 48 hours after the alert.

Measurements and Main Results:
For the 362 alerts triggered, 180 nurses (50% response rate) and 107 providers (30% response rate) completed the first survey. Of these, 43 nurses (24% response rate) and 44 providers (41% response rate) completed the second survey. Few (24% nurses, 13% providers) identified new clinical findings after responding to the alert. Perceptions of the presence of sepsis at the time of alert were discrepant between nurses (13%) and providers (40%). The majority of clinicians reported no change in perception of the patient’s risk for sepsis (55% nurses, 62% providers). A third of nurses (30%) but few providers (9%) reported the alert changed management. Almost half of nurses (42%) but less than a fifth of providers (16%) found the alert helpful at 6 hours.

Conclusions:
In general, clinical perceptions of Early Warning System 2.0 were poor. Nurses and providers differed in their perceptions of sepsis and alert benefits. These findings highlight the challenges of achieving acceptance of predictive and machine learning–based sepsis alerts.
Glomerular Hyper- and Hypofiltration During Acute Circulatory Failure: Iohexol-Based Gold-Standard Descriptive Study
Authors: Salmon Gandonnière Charlotte , Helms Julie , Le Tilly Olivier , Benz-de Bretagne Isabelle , Bretagnol Anne , Bodet-Contentin Laetitia , Mercier Emmanuelle , Halimi Jean-Michel , Benzékri-Lefèvre Dalila , Meziani Ferhat , Barin-Le Guellec Chantal , Ehrmann Stephan 
Published: May 2019

Objective:To assess glomerular filtration rate in the early phase of acute circulatory failure by measuring iohexol plasma clearance.Design:Interventional prospective multicentric study.Setting:Three French ICUs in tertiary teaching hospitals.Patients:Patients with acute circulatory failure within 12 hours after ICU admission.Interventions:IV administration of a nontoxic 5-mL dose of iohexol. Collection of nine arterial blood samples over 24 hours for iohexol plasma concentration measurements. Iohexol clearance calculation with a population pharmacokinetic model. Iohexol clearance was an estimation of the mean glomerular filtration rate over 24 hours.Measurements and Main Results:Among 99 included patients, we could calculate iohexol clearance for 85. The median iohexol clearance was 31 mL/min (interquartile range, 16–44). According to iohexol clearance, 41 patients (48%) had severe hypofiltration (clearance, < 30 mL/min), 29 (34%) had moderate hypofiltration, and 10 (12%) had mild hypofiltration (clearance, 30–60 and 60–90 mL/min, respectively). Four patients (5%) had normal glomerular filtration rate, and only one (1%) showed hyperfiltration (clearance, > 130 mL/min). Urinary creatinine clearance underestimated renal impairment in one patient out of two; the bias of iohexol clearance toward 24-hour urinary creatinine clearance over the same period was –18.1 mL/min (limits of agreement, –73.5 to 37.4).Conclusions:We demonstrated the feasibility of iohexol clearance measurement in unstable critically ill patients. Normal kidney function is exceptional during the early phase of acute circulatory failure. Glomerular filtration rate estimation by urinary creatinine clearance frequently fails to detect renal impairment. Hyperfiltration is very infrequent.