bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction of the Lymphedema Action Plan (LeAP): Clinical Advancement in Proactive Lymphedema Care
Authors: Beaman Renata
Published: October 2018

Background:

Breast cancer–related lymphedema (BCRL) is a disease secondary to the removal of, or damage to, lymph nodes that can increase emotional and physical burden, shoulder impairment, and functional disability in those affected by breast cancer. The multifactorial impact of lymphedema may also negatively affect quality of life.

Purpose:

Although research supports the role of early lymphedema education including the identification of lymphedema risk factors and early professional intervention, we do not yet have a risk management tool that directly links this information to self-directed treatment. The Lymphedema Action Plan (LeAP) was designed to fill this gap.

Design:

The LeAP is divided into 3 categories (green light, yellow light, and red light) that serve to link recognized risk reduction strategies and early signs and symptoms of lymphedema to established actions that can improve lymphedema outcomes. It was designed to empower those at risk for BCRL by educating patients and caregivers about (1) recognized risk factors and proactive behavior modification, (2) early signs and symptoms of lymphedema, (3) actions that can be taken to control an exacerbation, and (4) when to see a medical provider, with the ultimate goal of optimizing control of this incurable disease.
Identifying and Treating Opioid Side Effects
Authors: Moss Jonathan
Published: October 2018

Methylnaltrexone Reverses Chronic Opioid-induced Constipation: A Randomized, Controlled Trial. By Yuan CS, Foss JF, O’Connor M, Osinski J, Karrison T, Moss J, Roizen MF. JAMA 2000; 130:142–8. Reprinted with permission.

Context

Constipation is the most common chronic adverse effect of opioid pain medications in patients who require long-term opioid administration, such as patients with advanced cancer, but conventional measures for ameliorating constipation often are insufficient.

Objective

To evaluate the efficacy of methylnaltrexone, the first peripheral opioid receptor antagonist, in treating chronic methadone-induced constipation.

Design

Double-blind, randomized, placebo-controlled trial conducted between May 1997 and December 1998.

Setting

Clinical research center of a university hospital.

Participants

Twenty-two subjects (9 men and 13 women; mean [SD] age, 43.2 [5.5] years) enrolled in a methadone maintenance program and having methadone-induced constipation.

Main Outcome Measures

Laxation response, oral-cecal transit time, and central opioid withdrawal symptoms were compared between the 2 groups.

Results

The 11 subjects in the placebo group showed no laxation response, and all 11 subjects in the intervention group had laxation response after intravenous methylnaltrexone administration (P<.001). The oral-cecal transit times at baseline for subjects in the methylnaltrexone and placebo groups averaged 132.3 and 126.8 minutes, respectively. The average (SD) change in the methylnaltrexone-treated group was −77.7 (37.2) minutes, significantly greater than the average change in the placebo group (−1.4 [12.0] minutes; P<.001). No opioid withdrawal was observed in any subject, and no significant adverse effects were reported by the subjects during the study.

Conclusions

Our data demonstrate that intravenous methylnaltrexone can induce laxation and reverse slowing of oral cecal-transit time in subjects taking high opioid dosages. Low-dosage methylnaltrexone may have clinical utility in managing opioid-induced constipation.
Gait Analysis After Intertrochanteric Hip Fracture: Does Shortening Result in Gait Impairment?
Authors: Gausden Elizabeth B. , Sin Danielle , Levack Ashley E. , Wessel Lauren E. , Moloney Gele , Lane Joseph M. , Lorich Dean G.
Published: October 2018

Objective:

To determine the association between fracture collapse with altered gait after intertrochanteric (IT) fracture using the trochanteric fixation nail (TFN) and helical blade.

Design:

Prospective cohort study.

Setting:

Academic Level I trauma center.

Patients:

Seventy-two patients with IT hip fractures (OTA/AO 31) treated between 2012 and 2016. The average age was 79.7 years (range, 51–94 years); there were 59 women and 13 men.

Intervention:

All patients were treated with cephalomedullary nailing using the TFN (DePuy-Synthes, West Chester, PA) with a helical blade.

Main Outcome Measures:

At follow-up appointments, temporospatial gait parameters were measured and recorded. Radiographs were analyzed at the time of surgery and at each follow-up visit. Amount of radiographic femoral neck shortening was measured radiographically. Patients completed the Harris Hip Score, visual analog scale for pain, Short Form-36 Physical Component Score, and Short Form-36 Mental Component Score.

Results:

The mean length of follow-up between the surgery and the gait analysis was 8.6 months (±0.7 months). The mean amount of shortening was 4.7 mm (±0.6 mm). Out of the 72 patients analyzed, there were 15 patients (20.8%) who shortened more than 8 mm, 7 patients (9.7%) who shortened 10 mm or more, and 2 patients (2.8%) who shortened more than 20 mm. Mean shortening was 3.0 mm for stable OTA/AO 31-A1 fractures, whereas the unstable patterns (OTA/AO 31-A2, 31-A3) demonstrated a mean shortening of 5.9 mm (P = 0.02). There was significant correlation between increased shortening and decreased cadence (P = 0.008), increased double support time (P < 0.001), decreased step length (P = 0.001), and increased single support asymmetry (P = 0.04) during gait analysis. The threshold of 8 mm of shortening predicted decreased cadence (P = 0.008), increased double support time (P < 0.001), and decreased step length (P = 0.006). Analysis of patient-reported outcome scores, including the Harris Hip Score, visual analog scale, SF-36 Physical Component Score, and SF-36 Mental Component Score, revealed no significant association with shortening.

Conclusions:

Results from this study indicate that shortening after cephallomedullary nailing of IT hip fractures using the TFN with a helical blade is associated with altered gait, specifically decreased cadence, increased double support time, decreased step length, and increased single support time asymmetry.

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Surgical Fixation of Geriatric Sacral U-Type Insufficiency Fractures: A Retrospective Analysis
Authors: Pulley Benjamin R. , Cotman Steven B. , Fowler T. Ty
Published: October 2018

Objectives:

To define the incidence of sacral U-type insufficiency fracture and describe management of a consecutive series of patients with this injury.

Design:

Retrospective analysis.

Setting:

Single Level II trauma center.

Patients/Participants:

Sixteen adult patients with sacral U-type insufficiency fractures treated over a 36-month period.

Intervention:

Patients were indicated for percutaneous screw fixation of the posterior pelvis if they had posterior pelvic pain that prohibited mobilization.

Main Outcome Measurements:

Visual analog scale for pain, distance ambulated on postoperative day 1, and change in sacral kyphosis.

Results:

The sacral U-type insufficiency fracture incidence was 16.7% (19/114); average patient age was 75 years. Delayed surgery was performed after primary nonoperative treatment had failed in 62.5% (10/16) at an average 83 days postinjury. Acute surgery was performed in 37.5% (6/16) at an average 5 days postinjury. Distance ambulated on postoperative day 1 was 114.4 feet [95% confidence interval (CI) (50.6, 178.2)] and 88.7 feet [95% CI (2.8, 174.6)] in the delayed and acute surgery groups, respectively, P = 0.18. Change in visual analog scale for pain was −3.2 [95% CI (−5.0, −1.4)] and −3.7 [95% CI (−7.0, −0.4)] in the delayed and acute surgery groups, respectively, P = 0.15. Change in sacral kyphosis from presentation to surgery was 12.3 degrees [95% CI (6.7, 17.9)] and 0.3 degrees [95% CI (−0.2, 0.9)] in the delayed and acute surgery groups, respectively, P < 0.01. Minimum follow-up was 12 months.

Conclusions:

Treatment of sacral U-type insufficiency fractures by percutaneous screw fixation permits early mobilization, provides rapid pain relief, and prevents progressive deformity.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Interfacility Transfer Is a Risk Factor for Venous Thromboembolism in Lower Extremity Fracture Patients
Authors: Boyd Evan , Crespo Alexander , Hutzler Lorraine , Konda Sanjit , Egol Kenneth
Published: October 2018

Objective:

To compare the incidence of venous thromboembolism (VTE) among patients with pelvic and/or lower extremity fractures directly admitted to our institution versus those transferred from an outside hospital for definitive management.

Design:

Retrospective cohort.

Setting:

Tertiary care orthopaedic hospital.

Patients:

Six hundred ninety patients who received definitive care for a lower extremity fracture at our institution between 2010 and 2017.

Intervention:

Interfacility transfer for definitive management of pelvic or lower extremity fracture.

Main Outcome Measurements:

VTE incidence and time to surgery.

Results:

The interfacility transfer (TR) group comprised 126 patients, and the direct admission (DA) group comprised 564 patients. TR patients had a significantly higher incidence of VTE compared with the DA group: 9.5% versus 0.7%, respectively (P < 0.001). Time to surgery was also longer in the TR group compared with the DA group: 3.05 ± 3.00 days versus 2.16 ± 2.42 days, respectively (P = 0.005). Demographics for TR and DA did not significantly differ with regard to age, sex, length of stay, or American Society of Anesthesiologist score. In the TR group, no complete and explicit documentation regarding thromboprophylaxis administration while at the outside facility was found.

Conclusions:

Patients undergoing interfacility transfer for definitive management of pelvic and lower extremity fractures are at a significantly increased risk of the development of VTE.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Biomechanical Analysis of Superior and Anterior Precontoured Plate Fixation Techniques for Neer Type II-A Clavicle Fractures
Authors: Worhacz Kellen , Nayak Aniruddh N. , Boudreaux Robert L. , Pavan Beatrice , Wipf Dipl-Ing Felix , Jacofsky Marc C. , Araghi Arash
Published: October 2018

Objective:

There are limited biomechanical data supporting the use of anterior or superior-lateral precontoured clavicle plates for the treatment of displaced Neer type II-A clavicle fractures. The objectives of this study were as follows: (a) compare noncontoured versus precontoured superior plating; (b) compare use of locking versus nonlocking screws in the lateral fragment for superior precontoured plates; and (c) compare superior versus anterior precontoured plates with locking lateral fragment screws.

Methods:

The following constructs were tested on a synthetic clavicle model simulating a Neer type II-A fracture: (a) superior precontoured plate with locking (SUP-L, n = 6); (b) superior precontoured plate with nonlocking (SUP-NL, n = 8); (c) anterior precontoured plate with locking (ANT-L, n = 7); and (d) superior noncontoured locking compression plate (SUP-LCP, n = 6). Constructs were subjected to cyclical cantilever loads. Construct stiffness and survival (cycles to failure) were documented. Mann–Whitney U tests were performed for group-wise statistical comparison (α = 0.05) of data.

Results:

The SUP-L construct was significantly stiffer than both SUP-LCP and ANT-L constructs (P < 0.02). The SUP-NL construct was stiffer than the SUP-L (P = 0.03) construct. Both SUP-L and ANT-L precontoured constructs survived longer than the noncontoured SUP-LCP construct (P < 0.022). The SUP-L construct survived longer than the SUP-NL (P = 0.013) and the ANT-L (P = 0.008) constructs.

Conclusions:

Superior precontoured plates yielded biomechanically superior constructs compared with anterior precontoured and superior noncontoured plates. Using locking screws in the lateral fragment over nonlocking screws may improve overall superior precontoured plate construct survivability. However, our results were limited to a synthetic biomechanical model and require further investigation to establish a clinical correlation.
Decreased Reoperations and Improved Outcomes With Reverse Total Shoulder Arthroplasty in Comparison to Hemiarthroplasty for Geriatric Proximal Humerus Fractures: A Systematic Review and Meta-Analysis
Authors: Austin Daniel C. , Torchia Michael T. , Cozzolino Niki H. , Jacobowitz Lauren E. , Bell John-Erik
Published: October 2018

Objectives:

We sought to compare range of motion, clinical outcome scores, and complications after reverse total shoulder arthroplasty (RSA) and hemiarthroplasty (HA) in geriatric patients with acute proximal humerus fractures.

Data Sources:

We searched MEDLINE (1946–2017), EMBASE (1947–2017), the Cochrane Central Register of Controlled Trials (1898–2017) and ClinicalTrials.gov in October 2017. No limits were used in the database search. We also manually reviewed reference lists of included studies. We did not restrict studies based on language.

Study Selection:

We included all randomized controlled trials and cohort studies in which the study population had a mean age of 65 years or older, received RSA or HA to treat an acute proximal humerus fracture, and had a minimum follow-up of 6 months.

Data Extraction:

Two independent reviewers used a standardized data collection form to extract relevant information from included studies. Discrepancies were resolved by a consensus or a third party if consensus could not be reached. Study authors were contacted for missing or incomplete data.

Data Synthesis:

Using a random effects model, we calculated mean differences (MD) and standardized mean differences (SMD) for continuous outcomes; we calculated relative risk for dichotomous outcomes.

Results:

Fifteen studies were included in the meta-analysis, including 421 patients treated with RSA and 492 treated with HA for a total of 913 patients. Compared with HA, the RSA group had significantly improved pain scores (SMD = 0.74, P < 0.001), outcome scores (SMD = 0.63, P < 0.001), and forward flexion (MD = 24.3 degrees, P < 0.001). Compared with RSA, the HA group had a significantly increased risk of reoperation (relative risk = 2.8, P = 0.02). There were no differences between the groups with regard to external rotation (P = 0.31) or deep infection (P = 0.90).

Conclusions:

Aggregating available research suggests that RSA results in improved range of motion, clinical outcome scores, and rates of all-cause reoperation with no difference in infection rates. Using RSA for the treatment of acute proximal humerus fractures in the elderly population may result in improved short- and medium-term outcomes compared with HA. Future work should evaluate long-term outcomes to see if the benefits of RSA persist.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Risk Factors for Conversion to Total Hip Arthroplasty After Acetabular Fractures Involving the Posterior Wall
Authors: Firoozabadi Reza , Hamilton Benjamin , Toogood Paul , Routt Milton “Chip” , Shearer Dave
Published: October 2018

Objectives:

Identify risk factors for early conversion to total hip arthroplasty (THA) in an effort to aid in counseling patients and selecting the optimal treatment for patients who sustain a fracture involving the posterior wall of the acetabulum.

Design:

Retrospective cohort analysis.

Setting:

Level I trauma center.

Patients:

Patients with acetabular fractures involving the posterior wall managed with open reduction internal fixation at least 4 years out from surgery.

Intervention:

Preoperative and postoperative computed tomography scans were reviewed for injury characteristics and reduction quality. Participants were contacted by telephone to document reoperations and functional outcomes including the SF-8 and modified Merle d'Aubigne Hip Scale.

Main Outcome Measure:

Conversion to THA.

Results:

The overall rate of conversion to THA was 5% at 2 years, 14% at 5 years, and 17% at 9 years. Presence of 5 specific radiographic features was associated with a 50% rate of conversion to THA in contrast to 11% if 4 or less features were present. Among cases with less than 1 mm of diastasis/step-off on postoperative computed tomography scan, there were no THA conversions, 10% conversion for 1–4 mm, and 54% if 4 mm or more of malreduction. There was no difference in SF-8 or modified Merle d'Aubigne scores comparing patients who underwent THA and those who did not.

Conclusions:

Acetabular fractures with posterior wall involvement are associated with a significantly higher rate of conversion to THA if reduction is not near-anatomic. A combination of clinical/radiographic findings is associated with poorer reductions and higher rate of conversion to THA.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Clinical Outcomes and Complications of the Surgical Implant Generation Network (SIGN) Intramedullary Nail: A Systematic Review and Meta-Analysis
Authors: Usoro Andrew O. , Bhashyam Abhiram , Mohamadi Amin , Dyer George S. , Zirkle Lewis , von Keudell Arvind
Published: October 2018

Objectives:

This study is a systematic review and meta-analysis of the clinical outcomes and pooled complication rate of femoral, tibial, and humeral fracture fixation using SIGN nails. We aimed at comparing the pooled rate of adverse events based on the country of study origin, acute versus delayed fracture fixation, and length of follow-up.

Methods:

We searched PubMed/MEDLINE/Cochrane databases from 2000 to 2016 for English language studies. There was substantial heterogeneity among included studies. Therefore, we used subgroup analysis of varying adverse events and removal of potential outlier studies based on the “remove one” sensitivity analysis to address the heterogeneity across studies. A funnel plot was drawn and inspected visually to assess publication bias. We reported pooled complication rates for each adverse event with 95% prediction interval.

Results:

There were 14 studies with 47,169 cases across 58 different low- and middle-income countries. The average age was 33 ± 14 years, with 83% men and 17% women. Sixty percent of SIGN nails used in these 14 studies were used in femur fracture fixation, 38% in tibial shaft fractures, and the remaining 2% for humeral shaft fractures. Approximately 23% of patients had follow-up data recorded. All studies that measured clinical outcome indicated that >90% achieved full weight-bearing status, favorable range of motion (knee range of motion >90 degrees according to the SIGN database), and radiographic or clinical union depending on the specific variable(s) measured in each study. The overall complication rate was 5.2% (4.4%–6.4%). Malalignment (>5 degrees of angulation in any plane) was the most common complication (7.6%), followed by delayed/nonunion (6.9%), infection (5.9%), and hardware failure, (3.2%).

Conclusions:

Overall, the use of SIGN nails in fixing femoral, tibial, and humeral shaft fractures demonstrates good results with a high rate of return to full weight-bearing and radiographic/clinical union. The most common complications when using the SIGN nail are malalignment, delayed/nonunion, infection, and hardware failure.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Impact of Direct Oral Anticoagulants in Patients With Hip Fractures
Authors: Bruckbauer Martin , Prexl Oliver , Voelckel Wolfgang , Ziegler Bernhard , Grottke Oliver , Maegele Marc , Schöchl Herbert
Published: October 2018

Objective:

To assess the impact of direct oral anticoagulant (DOAC) intake compared with Coumadin (COU) in patients suffering hip fractures (HFs).

Design:

Retrospective cohort analysis.

Setting:

Level 1 Trauma Center.

Intervention:

Timing of surgical hip fixation.

Patients:

Three-hundred twenty patients 65 years of age or older with isolated HF were enrolled into the study: 207 (64.7%) without any antithrombotic therapy (no-ATT), 59 (18.4%) on COU, and 54 (16.9%) on DOACs.

Main Outcome Measurements:

Time to surgery, blood loss, mortality, hospital length of stay, red blood cell transfusion, use of reversal agents, and Charlson Comorbidity Index.

Results:

Patients on COU and DOACs had a higher Charlson Comorbidity Index compared with the no-ATT group (P < 0.0001). Despite the fact that significantly more patients received reversal agents in the COU group compared with DOAC medication (P < 0.0001), percentage of transfused patients were similar (54.2% vs. 53.7%). Time to surgery was significantly shorter in the no-ATT group when compared with DOAC patients (12–29.5 hours, respectively). No difference in postoperative hemorrhage, intensive care unit length of stay, and mortality was observed between groups.

Conclusions:

DOAC medication in HF patients caused long elapse time until surgical repair. We found no evidence of higher bleeding rates in HF patients on DOACs compared with COUs. Earlier HF fixation might be indicated in DOAC patients.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Self-Reported Recovery Likelihood Predicts Higher Physician Ratings: A Survey of Patients After Orthopaedic Surgery
Authors: Rascoe Alexander S. , Treiman Scott , Gunasekar Ashwath , Vallier Heather A.
Published: October 2018

Objectives:

What are the differences between elective and trauma patient satisfaction and do patient and diagnosis factors predict physician scores?

Design:

Prospective cohort study.

Setting:

Urban Level 1 Trauma center.

Patients/Participants:

Three hundred twenty-three trauma patients and 433 elective orthopaedic patients treated at our center by the same surgeons.

Intervention:

Trauma patients treated surgery for one or more fractures; elective patients treated with hip, knee, or shoulder arthroplasty, or rotator cuff repair.

Main Outcome Measurements:

Telephone survey regarding patient experience and satisfaction with their care. The survey included questions from Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys, and responses were rated on a 1–5 point Likert scale (5 best).

Results:

Elective surgery patients had mean age of 56.4 years, and trauma patients were mean 50.3 years of age. Trauma patients rated their likelihood to make a full recovery lower than elective patients (median, interquartile range), 5.0 (1.0) versus 4.0 (2.0) (P < 0.001). After multivariate binary logistic regression, patients who rated the hospital higher (≥4 vs. ≤3) were more likely (odds ratio = 10.0, 95% confidence interval, 6.4–15.8) to score physicians better. Similarly, patients who scored their overall likelihood of recovering ≥4 compared with ≤3 were more likely (odds ratio = 3.6, 95% confidence interval, 2.9–5.6) to rate their physicians more positively.

Conclusions:

Patient perceptions including their likelihood to make a full recovery and their overall impression of the hospital predicted higher physician scores. We conclude that these physician scores are subject to patient perception biases and are not independent of the overall care experience. We recommend HCAHPS and physician ratings' web sites include internal controls, such as the patient perception of overall likelihood to recover, to aid in interpreting survey results.
Intraoperative Assessment of Coronal Alignment in Distal Femur Fracture Fixation: Technical Trick
Authors: Scott Brandon R. , Wright Raymond D. , Moghadamian Eric S.
Published: October 2018

Supracondylar femur fractures represent a challenging and common injury treated by many orthopedic surgeons. An array of surgical fixation options has been developed to help the treating surgeon restore normal anatomic alignment of these fractures, and lateral precontoured condylar femoral locking plates have become a common implant for most surgeons in treating these fractures. Although these precontoured plates provide significant benefit to the treating physician in regards to gaining appropriate bony fixation, common technical errors that may lead to malalignment when using these plates have been described. Avoiding these errors will help improve patient outcomes. Here, we describe a novel, inexpensive, and universally available technique that may aid the treating surgeon in restoring coronal alignment when treating distal femur fractures.
Reverse Shoulder Arthroplasty in Acute Fractures of the Proximal Humerus: Does Tuberosity Healing Improve Clinical Outcomes?
Authors: Reuther Falk , Petermann Martin , Stangl Richard
Published: October 2018

Objective:

To evaluate the clinical outcomes of reverse shoulder arthroplasty (RSA) in elderly patients with proximal humeral fractures and assess the role of tuberosity healing on the outcome.

Design:

Case series.

Setting:

Multicenter clinical study of Level-2 trauma centers.

Patients/Participants:

We included 81 patients with a mean age of 78.5 ± 6.5 years (range, 58.5–90.9 years) and a nonreconstructable proximal humeral fracture.

Intervention:

Modular reverse fracture shoulder arthroplasty.

Main Outcome Measurements:

We determined range of motion, constant score, and the American Shoulder and Elbow Surgeons Shoulder Score as clinical outcomes and evaluated tuberosity healing at 6 weeks, 6 months, 1 year, and 2 years.

Results:

Tuberosities healed in most patients; 37 patients had completely healed tuberosities, and 33 patients had partially healed tuberosities, whereas 11 patients had unhealed tuberosities. However, no significant differences were found in the functional outcomes among the 3 groups (P > 0.05).

Conclusions:

Our results with a modular reverse prosthesis confirmed similar constant scores, American Shoulder and Elbow Surgeons Shoulder Scores, and tuberosity healing rates as reported in the current clinical evidence for RSA. We could not confirm that tuberosity healing improved functional outcomes; however, it should be noted that tuberosity healing was assessed using standard radiographs. Nevertheless, our study strengthens the consensus that RSA can be recommended for well-selected elderly patients with complex displaced proximal humeral fractures.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
The Effects of Storage Age of Blood in Massively Transfused Burn Patients: A Secondary Analysis of the Randomized Transfusion Requirement in Burn Care Evaluation Study
Authors: Cartotto Robert , Taylor Sandra L. , Holmes James H. , Peck Michael , Cochran Amalia , King Booker T. , Bhavsar Daval , Tredget Edward E. , Mozingo David , Greenhalgh David , Pollock Brad H. , Palmieri Tina L.
Published: October 2018

Objectives:

Major trials examining storage age of blood transfused to critically ill patients administered relatively few blood transfusions. We sought to determine if the storage age of blood affects outcomes when very large amounts of blood are transfused.

Design:

A secondary analysis of the multicenter randomized Transfusion Requirement in Burn Care Evaluation study which compared restrictive and liberal transfusion strategies.

Setting:

Eighteen tertiary-care burn centers.

Patients:

Transfusion Requirement in Burn Care Evaluation evaluated 345 adults with burns greater than or equal to 20% of the body surface area. We included only the 303 patients that received blood transfusions.

Interventions:

The storage ages of all transfused red cell units were collected during Transfusion Requirement in Burn Care Evaluation. A priori measures of storage age were the the mean storage age of all transfused blood and the proportion of all transfused blood considered very old (stored ≥ 35 d).

Measurements and Main Results:

The primary outcome was the severity of multiple organ dysfunction. Secondary outcomes included time to wound healing, the duration of mechanical ventilation, and in-hospital mortality. There were 6,786 red cell transfusions with a mean (± sd) storage age of 25.6 ± 10.2 days. Participants received a mean of 23.4 ± 31.2 blood transfusions (range, 1–219) and a mean of 5.3 ± 10.7 units of very old blood. Neither mean storage age nor proportion of very old blood had any influence on multiple organ dysfunction severity, time to wound healing, or mortality. Duration of ventilation was significantly predicted by both mean blood storage age and the proportion of very old blood, but this was of questionable clinical relevance given extreme variability in duration of ventilation (adjusted r
2 ≤ 0.01).

Conclusions:

Despite massive blood transfusion, including very old blood, the duration of red cell storage did not influence outcome in burn patients. Provision of the oldest blood first by Blood Banks is rational, even for massive transfusion.
Incidence and Prevalence of Delirium Subtypes in an Adult ICU: A Systematic Review and Meta-Analysis*
Authors: Krewulak Karla D. , Stelfox Henry T. , Leigh Jeanna Parsons , Ely E. Wesley , Fiest Kirsten M.
Published: October 2018

Objectives:

Use systematic review and meta-analytic methodology to estimate the pooled incidence, prevalence, and proportion of delirium cases for each delirium subtype (hypoactive, hyperactive, and mixed) in an adult ICU population.

Data Sources:

We conducted a search of the MEDLINE, EMBASE, CINAHL, SCOPUS, Web of Science, and PsycINFO databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards from database inception until October 22, 2017, with no restrictions.

Study Selection:

We included original research conducted in adults admitted to any medical, surgical, or speciality ICU that reported incidence or prevalence estimates of delirium according to delirium subtype.

Data Extraction:

Data were extracted on sample size, population demographics, condition information, and reported delirium estimates.

Data Synthesis:

Forty-eight studies (27,342 patients; 4,550 with delirium) with an overall pooled prevalence of 31% (95% CI, 24–41; I

2
= 99%) met inclusion criteria. The pooled incidence (n = 18 studies) of delirium subtypes were hyperactive (4% [95% CI, 2–6]; I
2 = 92%]), hypoactive (11% [95% CI, 8–17; I
2 = 97%]), and mixed (7% [95% CI, 4–11; I
2 = 97%]). The pooled prevalence (n = 31 studies) of delirium subtypes were hyperactive (4% [95% CI, 3–6; I
2 = 94%]), hypoactive (17% [95% CI, 13–22; I
2 = 97%]), and mixed (10% [95% CI, 6–16; I
2 = 99%]). The pooled prevalence of hypoactive delirium in study populations with a similarly high severity of illness or mechanically ventilated was higher (severity of illness: 29% [95% CI, 18–46%; I

2
= 95%], 100% mechanically ventilated: 35% [95% CI, 23–55%; I

2
= 93%]) compared with the pooled prevalence of hypoactive delirium.

Conclusions:

Despite significant heterogeneity between studies, these data show the majority of delirious ICU patients to have hypoactive delirium, a finding with potential monitoring, management, and prognostic implications. The prevalence of hypoactive delirium varies between-study populations and is higher in patients with greater severity of illness.
Renal Klotho is Reduced in Septic Patients and Pretreatment With Recombinant Klotho Attenuates Organ Injury in Lipopolysaccharide-Challenged Mice
Authors: Jou-Valencia Daniela , Molema Grietje , Popa Eliane , Aslan Adnan , van Dijk Fransien , Mencke Rik , Hillebrands Jan-Luuk , Heeringa Peter , Hoenderop Joost G. , Zijlstra Jan G. , van Meurs Matijs , Moser Jill
Published: October 2018

Objectives:

To determine the applicability of recombinant Klotho to prevent inflammation and organ injury in sepsis in man and mice.

Design:

Prospective, clinical laboratory study using “warm” human postmortem sepsis-acute kidney injury biopsies. Laboratory study using a mouse model of endotoxemia.

Setting:

Research laboratory at a university teaching hospital.

Subjects:

Adult patients who died of sepsis in the ICU and control patients undergoing total nephrectomy secondary to renal cancer; male C57BL/6 and Klotho haploinsufficient mice.

Interventions:

Lipopolysaccharide (0.05 mg/kg) injection and kill after 4, 8, and 24 hours. Mice received recombinant Klotho (0.05 mg/kg) 30 minutes prior to lipopolysaccharide (1 mg/kg) injection. Mice treated with saline were included as controls.

Measurements and Main Results:

Quantitative reverse transcription polymerase chain reaction and immunohistochemical staining were used to quantify Klotho messenger RNA and protein expression in the kidney of sepsis-acute kidney injury patients and the kidney and brain of mice. The messenger RNA and protein expression of damage markers, inflammatory cytokine, chemokines, and endothelial adhesion molecules were also determined in mice. Renal neutrophil influx was quantified. We found significantly lower renal Klotho messenger RNA and protein levels in sepsis-acute kidney injury biopsies than in control subjects. These findings were recapitulated in the kidney and brain of lipopolysaccharide-challenged mice. Decreased Klotho expression paralleled an increase in kidney damage markers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Administration of recombinant Klotho prior to lipopolysaccharide injection attenuated organ damage, inflammation and endothelial activation in the kidney and brain of mice. Furthermore, less neutrophils infiltrated into the kidneys of recombinant Klotho mice compared with lipopolysaccharide only treated mice.

Conclusions:

Renal Klotho expression in human sepsis-acute kidney injury and in mouse models of sepsis was significantly decreased and correlated with renal damage. Recombinant Klotho intervention diminished organ damage, inflammation, and endothelial activation in the kidney and brain of lipopolysaccharide-challenged mice. Systemic Klotho replacement may potentially be an organ-protective therapy for septic patients to halt acute, inflammatory organ injury.
Meaning of Intracranial Pressure-to-Blood Pressure Fisher-Transformed Pearson Correlation–Derived Optimal Cerebral Perfusion Pressure: Testing Empiric Utility in a Mechanistic Model
Authors: Akhondi-Asl Alireza , Vonberg Frederick W. , Au Cheuk C. , Tasker Robert C.
Published: October 2018

Objectives:

Time-averaged intracranial pressure-to-blood pressure Fisher-transformed Pearson correlation (PRx) is used to assess cerebral autoregulation and derive optimal cerebral perfusion pressure. Empirically, impaired cerebral autoregulation is considered present when PRx is positive; greater difference between time series median cerebral perfusion pressure and optimal cerebral perfusion pressure (Δ
CPP) is associated with worse outcomes. Our aims are to better understand: 1) the potential strategies for targeting optimal cerebral perfusion pressure; 2) the relationship between cerebral autoregulation and PRx; and 3) the determinants of greater Δ
CPP.

Design:

Mechanistic simulation using a lumped compartmental model of blood pressure, intracranial pressure, cerebral autoregulation, cerebral blood volume, Paco
2, and cerebral blood flow.

Setting:

University critical care integrative modeling and precision physiology research group.

Subjects:

None, in silico studies.

Interventions:

Simulations in blood pressure, intracranial pressure, Paco
2, and impairment of cerebral autoregulation, with examination of “output” cerebral perfusion pressure versus PRx-plots, optimal cerebral perfusion pressure, and Δ
CPP.

Measurements and Main Results:

In regard to targeting optimal cerebral perfusion pressure, a shift in mean blood pressure or mean intracranial pressure with no change in mean blood pressure, with intact cerebral autoregulation, impacts optimal cerebral perfusion pressure. Second, a positive PRx occurs even with intact cerebral autoregulation. In relation to Δ
CPP, for a given input blood pressure profile, with constant intracranial pressure, altering the degree of impairment in cerebral autoregulation or the level of Paco
2 maintains differences to within ±5 mm Hg. Change in intracranial pressure due to either an intermittently prolonged pattern of raised intracranial pressure or terminal escalation shows Δ
CPP greater than 10 mm Hg and less than –10 mm Hg, respectively.

Conclusions:

These mechanistic simulations provide insight into the empiric basis of optimal cerebral perfusion pressure and the significance of PRx and Δ
CPP. PRx and optimal cerebral perfusion pressure deviations do not directly reflect changes in cerebral autoregulation but are, in general, related to the presence of complex states involving well-described clinical progressions with raised intracranial pressure.
Minimal Impact of Implemented Early Warning Score and Best Practice Alert for Patient Deterioration*
Authors: Bedoya Armando D. , Clement Meredith E. , Phelan Matthew , Steorts Rebecca C. , O’Brien Cara , Goldstein Benjamin A.
Published: October 2018

Objectives:

Previous studies have looked at National Early Warning Score performance in predicting in-hospital deterioration and death, but data are lacking with respect to patient outcomes following implementation of National Early Warning Score. We sought to determine the effectiveness of National Early Warning Score implementation on predicting and preventing patient deterioration in a clinical setting.

Design:

Retrospective cohort study.

Setting:

Tertiary care academic facility and a community hospital.

Patients:

Patients 18 years old or older hospitalized from March 1, 2014, to February 28, 2015, during preimplementation of National Early Warning Score to August 1, 2015, to July 31, 2016, after National Early Warning Score was implemented.

Interventions:

Implementation of National Early Warning Score within the electronic health record and associated best practice alert.

Measurements and Main Results:

In this study of 85,322 patients (42,402 patients pre-National Early Warning Score and 42,920 patients post-National Early Warning Score implementation), the primary outcome of rate of ICU transfer or death did not change after National Early Warning Score implementation, with adjusted hazard ratio of 0.94 (0.84–1.05) and 0.90 (0.77–1.05) at our academic and community hospital, respectively. In total, 175,357 best practice advisories fired during the study period, with the best practice advisory performing better at the community hospital than the academic at predicting an event within 12 hours 7.4% versus 2.2% of the time, respectively. Retraining National Early Warning Score with newly generated hospital-specific coefficients improved model performance.

Conclusions:

At both our academic and community hospital, National Early Warning Score had poor performance characteristics and was generally ignored by frontline nursing staff. As a result, National Early Warning Score implementation had no appreciable impact on defined clinical outcomes. Refitting of the model using site-specific data improved performance and supports validating predictive models on local data.
Combining National Early Warning Score With Soluble Urokinase Plasminogen Activator Receptor (suPAR) Improves Risk Prediction in Acute Medical Patients: A Registry-Based Cohort Study*
Authors: Rasmussen Line J. H. , Ladelund Steen , Haupt Thomas H. , Ellekilde Gertrude E. , Eugen-Olsen Jesper , Andersen Ove
Published: October 2018

Objectives:

Soluble urokinase plasminogen activator receptor is a prognostic biomarker associated with critical illness, disease progression, and risk of mortality. We aimed to evaluate whether soluble urokinase plasminogen activator receptor adds prognostic value to a vital sign-based score for clinical monitoring of patient risk (National Early Warning Score) in acute medical patients.

Design:

Registry-based observational cohort study of consecutively admitted acute medical patients.

Setting:

The Acute Medical Unit, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark.

Patients:

Acute medical patients admitted between November 18, 2013, and September 30, 2015.

Interventions:

None.

Measurements and Main Results:

Of 17,312 included patients, admission National Early Warning Score was available for 16,244 (93.8%). During follow-up, 587 patients (3.4%) died in-hospital, 859 (5.0%) within 30 days, and 1,367 (7.9%) within 90 days. High soluble urokinase plasminogen activator receptor was significantly associated with in-hospital-, 30-day-, and 90-day mortality within all National Early Warning Score groups, in particular in patients with a low National Early Warning Score; for 30-day mortality, mortality rate ratios ranged from 3.45 (95% CI, 2.91–4.10) for patients with National Early Warning Score 0–1, to 1.86 (95% CI, 1.47–2.34) for patients with National Early Warning Score greater than or equal to 9 for every doubling in soluble urokinase plasminogen activator receptor (log2-transformed). Combining National Early Warning Score, age, and sex with soluble urokinase plasminogen activator receptor improved prediction of in-hospital-, 30-day-, and 90-day mortality, increasing the area under the curve (95% CI) for 30-day mortality from 0.86 (0.85–0.87) to 0.90 (0.89–0.91), p value of less than 0.0001, with a negative predictive value of 99.0%.

Conclusions:

The addition of soluble urokinase plasminogen activator receptor to National Early Warning Score significantly improved risk prediction of both low- and high-risk acute medical patients. Patients with low National Early Warning Score but elevated soluble urokinase plasminogen activator receptor had mortality risks comparable to that of patients with higher National Early Warning Score.
Adenosine Triphosphate Release is Required for Toll-Like Receptor-Induced Monocyte/Macrophage Activation, Inflammasome Signaling, Interleukin-1β Production, and the Host Immune Response to Infection
Authors: Lee Albert H. , Ledderose Carola , Li Xiaoou , Slubowski Christian J. , Sueyoshi Koichiro , Staudenmaier Laura , Bao Yi , Zhang Jingping , Junger Wolfgang G.
Published: October 2018

Objectives:

Monocytes and macrophages produce interleukin-1β by inflammasome activation which involves adenosine triphosphate release, pannexin-1 channels, and P2X7 receptors. However, interleukin-1β can also be produced in an inflammasome-independent fashion. Here we studied if this mechanism also involves adenosine triphosphate signaling and how it contributes to inflammasome activation.

Design:

In vitro studies with human cells and randomized animal experiments.

Setting:

Preclinical academic research laboratory.

Subjects:

Wild-type C57BL/6 and pannexin-1 knockout mice, healthy human subjects for cell isolation.

Interventions:

Human monocytes and U937 macrophages were treated with different inhibitors to study how purinergic signaling contributes to toll-like receptor-induced cell activation and interleukin-1β production. Wild-type and pannexin-1 knockout mice were subjected to cecal ligation and puncture to study the role of purinergic signaling in interleukin-1β production and host immune defense.

Measurements and Main Results:

Toll-like receptor agonists triggered mitochondrial adenosine triphosphate production and adenosine triphosphate release within seconds. Inhibition of mitochondria, adenosine triphosphate release, or P2 receptors blocked p38 mitogen-activated protein kinase and caspase-1 activation and interleukin-1β secretion. Mice lacking pannexin-1 failed to activate monocytes, to produce interleukin-1β, and to effectively clear bacteria following cecal ligation and puncture.

Conclusions:

Purinergic signaling has two separate roles in monocyte/macrophage activation, namely to facilitate the initial detection of danger signals via toll-like receptors and subsequently to regulate nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 inflammasome activation. Further dissection of these mechanisms may reveal novel therapeutic targets for immunomodulation in critical care patients.
Parental Distress and Stress in Association with Health-Related Quality of Life in Youth with Spina Bifida: A Longitudinal Study
Authors: Driscoll Colleen F. Bechtel , Buscemi Joanna , Holmbeck Grayson N.
Published: October 2018

Objective:

This study examined associations between 3 distinct parent factors (parent personal distress, parenting stress, and spina bifida (SB)-specific parenting stress) and youth and parent proxy reports of youth health-related quality of life (HRQOL) over time.

Method:

Participants were recruited as part of a longitudinal study, and data were collected at 3 time points, spaced 2 years apart. Parents and youth completed questionnaires, and youth completed neuropsychological assessment tasks to determine youth intelligence quotient during home visits.

Results:

Analyses revealed that higher levels of maternal SB-specific parenting stress were related to lower levels of youth-reported HRQOL at time 1. Other parent factors were not associated with youth report of HRQOL at the earlier time points, although higher levels of maternal SB-specific parenting stress and paternal parenting stress were associated with lower levels of youth HRQOL at time 3. For mothers and fathers, increased parent personal distress, parenting stress, and SB-specific parenting stress were associated with decreased proxy report of youth HRQOL. Of these three parent factors, SB-specific parenting stress was consistently the most strongly associated with parent proxy-report of youth HRQOL.

Conclusion:

Parenting stress and distress are important targets for interventions, and these interventions may improve youth outcomes, especially as youth age. Future research is needed to identify other factors influencing youth HRQOL over time.
A Young Man with Trisomy 21 and Sudden Behavioral Changes
Authors: Cormier DePorres , Jean Davidson Emily , Young Amy , Augustyn Marilyn
Published: October 2018

CASE:

Grant is a 13-year-old boy with trisomy 21 who presents with his mother for concerns regarding the emergence of several new disruptive behaviors. While he is verbal, he also communicates through an augmentative communication device. He currently attends a residential school. Over the past 2 months, he has begun spitting at the staff, engaging in self-injurious behaviors, placing his hands in his pants, and frequently talking about “pee and poop.” Notably, Grant has undergone several changes to his educational placement and medical health over the past several months. He recently transferred to his current residential school from another placement to be closer to his family, although this has meant that Grant was unable to work with his long-time aide. Additionally, most of the students at Grant's current school are significantly lower functioning than him, such that Grant is one of the few verbal children.

Approximately 3 months ago, Grant underwent significant dental work under anesthesia. Grant had previously taken an alpha-agonist for behavioral management, although he was weaned off this 4 months ago because of increasing somnolence increasing somnolence. Grant's recent behavioral challenges make performing community and home activities more challenging.

Grant's behavioral history is notable for a previous episode of behavioral and emotional challenges 18 months ago. This occurred in the setting of transitioning to a new classroom with higher academic and behavioral expectations and decreased time spent with his family. These behaviors had consisted of self-injurious behaviors and tantrums consisting of crying and social withdrawal. This was managed by increased behavioral and academic supports via trained teachers and aides, medication management, and optimizing his augmentative communication. After these interventions, Grant's behavioral and emotional functioning improved and remained stable until this current episode.

Grant's mother is concerned about what may be causing these emerging behaviors and wondering if any of the recent educational and medical stressors could be contributing. What do you do next?