bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale, Methodological Quality, and Reporting of Cluster-Randomized Controlled Trials in Critical Care Medicine: A Systematic Review
Authors: Cook David J. , Rutherford William B. , Scales Damon C. , Adhikari Neill K. J. , Cuthbertson Brian H. 
Published: February 2021

OBJECTIVE:
Compared with individual-patient randomized controlled trials, cluster randomized controlled trials have unique methodological and ethical considerations. We evaluated the rationale, methodological quality, and reporting of cluster randomized controlled trials in critical care studies.

DATA SOURCES:
Systematic searches of Medline, Embase, and Cochrane Central Register were performed.

STUDY SELECTION:
We included all cluster randomized controlled trials conducted in adult, pediatric, or neonatal critical care units from January 2005 to September 2019.

DATA EXTRACTION:
Two reviewers independently screened citations, reviewed full texts, protocols, and supplements of potentially eligible studies, abstracted data, and assessed methodology of included studies.

DATA SYNTHESIS:
From 1,902 citations, 59 cluster randomized controlled trials met criteria. Most focused on quality improvement (24, 41%), antimicrobial therapy (9, 15%), or infection control (9, 15%) interventions. Designs included parallel-group (25, 42%), crossover (21, 36%), and stepped-wedge (13, 22%). Concealment of allocation was reported in 21 studies (36%). Thirteen studies (22%) reported at least one method of blinding. The median total sample size was 1,660 patients (interquartile range, 813–4,295); the median number of clusters was 12 (interquartile range, 5–24); and the median patients per cluster was 141 (interquartile range, 54–452). Sample size calculations were reported in 90% of trials, but only 54% met Consolidated Standards of Reporting Trials guidance for sample size reporting. Twenty-seven of the studies (46%) identified a fixed number of available clusters prior to trial commencement, and only nine (15%) prespecified both the number of clusters and patients required to detect the expected effect size. Overall, 36 trials (68%) achieved the total prespecified sample size. When analyzing data, 44 studies (75%) appropriately adjusted for clustering when analyzing the primary outcome. Only 12 (20%) reported an intracluster coefficient (median 0.047 [interquartile range, 0.01–0.13]).

CONCLUSIONS:
Cluster randomized controlled trials in critical care typically involve a small and fixed number of relatively large clusters. The reporting of key methodological aspects of these trials is often inadequate.
Lambert–Eaton Myasthenic Syndrome and Dermatomyositis With Anti–TIF1-gamma Autoantibody: A Unique Association of Autoimmune Neuromuscular Conditions Without Malignancy
Authors: Isfort Michael , Mnatsakanova Diana , Oddis Chester , Lacomis David 
Published: February 2021

Abstract
Lambert–Eaton myasthenic syndrome (LEMS) is a presynaptic neuromuscular junction disorder, and dermatomyositis (DM) is an idiopathic inflammatory myopathy. LEMS and DM are uncommon conditions that can present similarly and are often associated with autoantibodies. Concomitant LEMS and DM have only been reported a few times, and most of those cases were paraneoplastic. We present the first reported case of a patient with antivoltage gated calcium channel antibody positive LEMS who subsequently developed DM with antitranscription intermediary factor 1-gamma (anti–TIF1-γ) antibodies. Interestingly, both conditions occurred without evidence of malignancy. This diagnosis of LEMS and DM with characteristic clinical, electrodiagnostic, and histopathological evidence led to a beneficial modification of the patient's therapeutic regimen. Due to the fact that overlapping concurrent neuromuscular conditions are rare, a high clinical suspicion is needed to identify, evaluate (including appropriate cancer screenings), and appropriately treat these patients.
Machine Learning for Causal Inference: On the Use of Cross-fit Estimators
Authors: Zivich Paul N. , Breskin Alexander 
Published: February 2021

Background:
Modern causal inference methods allow machine learning to be used to weaken parametric modeling assumptions. However, the use of machine learning may result in complications for inference. Doubly robust cross-fit estimators have been proposed to yield better statistical properties.

Methods:
We conducted a simulation study to assess the performance of several different estimators for the average causal effect. The data generating mechanisms for the simulated treatment and outcome included log-transforms, polynomial terms, and discontinuities. We compared singly robust estimators (g-computation, inverse probability weighting) and doubly robust estimators (augmented inverse probability weighting, targeted maximum likelihood estimation). We estimated nuisance functions with parametric models and ensemble machine learning separately. We further assessed doubly robust cross-fit estimators.

Results:
With correctly specified parametric models, all of the estimators were unbiased and confidence intervals achieved nominal coverage. When used with machine learning, the doubly robust cross-fit estimators substantially outperformed all of the other estimators in terms of bias, variance, and confidence interval coverage.

Conclusions:
Due to the difficulty of properly specifying parametric models in high-dimensional data, doubly robust estimators with ensemble learning and cross-fitting may be the preferred approach for estimation of the average causal effect in most epidemiologic studies. However, these approaches may require larger sample sizes to avoid finite-sample issues.
Partial Ear Reconstruction with a Prelaminated Induced Expanded Radial Artery Flap
Authors: Flaherty Federico , Militelli Federico , Vizcay Macarena 
Published: February 2021

Summary:
A 76-year-old man underwent an extensive resection for squamous cell carcinoma 2 years before, resulting in the loss of the superior half of the right ear, without any attempt at reconstruction. The decision was to reconstruct with a combined suprafascial tissue expansion, an alloplastic framework fabricated with porous polyethylene, and a radial artery free flap. At 1-year follow-up, the patient was satisfied with the result. We believe this represents a novel approach to be considered for partial ear reconstruction.
Physician Burnout: Solutions for Individuals and Organizations
Authors: Carrau Diana , Janis Jeffrey E. 
Published: February 2021

Summary:
Burnout in medicine has become a national epidemic, affecting greater than one third of physicians, and yet physicians, departments, and institutions remain ill equipped to address it. Burnout is a syndrome characterized by emotional exhaustion, depersonalization, and a reduced sense of accomplishment that occurs as a response to one’s environment. We have a moral and ethical imperative to address physician burnout, as it has immense implications within healthcare. Solutions have historically focused on changing the behavior of the individual, but research has demonstrated that long-lasting change is brought about by intervening at the organizational level, which requires that leadership champion these efforts. Departmental and hospital leadership play a critical role in addressing the drivers of burnout. Here, we outline evidence-based strategies to combat physician burnout at both the individual and organizational levels and review what has been explored within the field of plastic surgery.
Legislation, Market Size, and Access to Gender-affirming Genital Surgery in the United States
Authors: Dagi Alexander F. , Boskey Elizabeth R. , Nuzzi Laura C. , Kang Christine O. , Ganor Oren , Labow Brian I. , Taghinia Amir H. 
Published: February 2021

Background:
The value of gender-affirming genital surgery (GAGS) has been established for certain transgender or gender non-conforming patients. This study aimed to determine the availability of GAGS by state and region in the United States, and to query possible associations of access to care with healthcare legislation and local market size.

Methods:
This was a cross-sectional study reporting on the distribution of hospitals and private practices offering GAGS in the United States. A list of prospective gender surgeons was compiled from 18 online databases. All surgeons were individually verified and were excluded if they did not perform phalloplasty, metoidioplasty, or vaginoplasty. Pertinent legislative and transgender or gender non-conforming population data were derived from the Movement Advancement Project and the Williams Institute.

Results:
Seventy-one practices in the United States offered GAGS in 2019. Forty-seven percent of states did not have a practice offering GAGS. A large prospective transgender or gender non-conforming market size increased the odds of GAGS availability in a state more than did local healthcare legislation supporting insurance coverage for gender-affirming care in 2019.

Conclusions:
Access to gender-affirming genital surgery was highly disparate in 2019. Factors that predicted access to care, including state healthcare legislation and prospective market sizes, may indicate strategies for overcoming disparities.
Post-Cesarean Section Pyoderma Gangrenosum Presenting with Vasopressor-dependent Shock: Long-term Follow-up after Delayed Primary Closure
Authors: Zolper Elizabeth G. , Harbour Patrick W. , Dekker Paige K. , Schwitzer Jonathan A. , Viramontes Ariel , Evans Karen K. 
Published: February 2021

Summary:
A 28-year-old woman with poor wound healing and surgical site pain presented 5 days post-cesarean section (post-CS) with vasopressor-dependent shock and was eventually diagnosed with postoperative pyoderma gangrenosum (PG). A worsening clinical picture consistent with presumed necrotizing infection necessitated surgical debridement. The patient was ultimately taken to the operating room 4 times with transient improvement after the operations when she received perioperative corticosteroids. We were unable to identify an infectious source and cultures revealed no microorganisms. Dermatopathology revealed neutrophilic infiltrate and focal necrosis without microorganisms. The biopsy site began to concurrently exhibit pathergic changes, leading to a diagnosis of PG. Twelve weeks later, she underwent DPC of her abdominal wound while maintained on an immunosuppressive regimen of cyclosporine and prednisone. Incisional negative pressure wound therapy with a small window was used in the immediate postoperative period to allow for direct visualization of the closed incision. She healed without issue and her immunosuppressive regimen was ultimately discontinued. Postoperative PG is an uncommon diagnosis with high risk of morbidity. It is often mistaken for necrotizing infection. We report a unique case of post-CS PG presenting as vasopressor-dependent shock that was successfully closed with incisional negative pressure wound therapy with a small window.
Immediate Lymphatic Reconstruction: Technical Points and Literature Review
Authors: Coriddi Michelle , Mehrara Babak , Skoracki Roman , Singhal Dhruv , Dayan Joseph H. 
Published: February 2021

Summary:
Recent studies have provided evidence that lymphovenous bypass—microsurgical re-routing of divided lymphatics to an adjacent vein—performed at the time of lymph node dissection decreases the rate of lymphedema development. Immediate lymphatic reconstruction in this setting is technically demanding, and there is a paucity of literature describing the details of the surgical procedure. In this report, we review the literature supporting immediate lymphatic reconstruction and provide technical details to demystify the operation for surgeons who wish to provide this option to their patients.
Targeted Muscle Reinnervation to Expendable Motor Nerves for the Treatment of Refractory Symptomatic Neuromas in Nonamputees
Authors: Chang Brian L. , Harbour Patrick , Mondshine Josh , Kleiber Grant M. 
Published: February 2021

Summary:
Symptomatic neuromas can cause debilitating pain, significantly impairing patients’ quality of life. There are numerous medical and surgical options for management. Targeted muscle reinnervation (TMR) is a nerve transfer procedure that is now commonly used to prevent or treat symptomatic neuromas or phantom limb pain in amputees. There are a few reports in the current literature about performing TMR in the nonamputee, but no cohort studies to date that report pain outcomes. This study evaluates TMR to treat symptomatic neuromas in nonamputee patients. This is a retrospective cohort study of all patients with symptomatic neuromas treated with TMR over a 1-year period from January 1,2019, to January 1, 2020, at MedStar Georgetown University Hospital. The neuromas are excised to healthy nerve fascicles, and a redundant donor motor fascicle is selected for nerve transfer. Patients were asked in clinic or via telephone about their preoperative and postoperative pain, function, and quality of life, and postoperative clinic notes were reviewed for complications and motor deficits. Fifteen patients were included in this study. Patients had symptomatic neuromas involving the upper extremity, lower extremity, and trunk. Pain frequency decreased from 6.7 times per week to 3.9 (P < 0.01) and from 9.1 times per day to 5.1 (P < 0.01). Pain severity decreased from an average of 7.9/10 to 4.3/10 (P < 0.01). Overall physical function increased from 3.7/10 to 5.8/10 (P = 0.01), and overall quality of life increased from 4.9/10 to 7.0/10 (P < 0.01). No patients had demonstrable weakness of the motor function of the donor nerve. Targeted muscle reinnervation is a viable surgical option for the treatment of symptomatic neuromas, particularly in those patients who have previously failed prior neuroma excisions.
SURGICAL OUTCOMES OF VITREOMACULAR TRACTION TREATED WITH FOVEAL-SPARING PEELING OF THE INTERNAL LIMITING MEMBRANE
Authors: Morescalchi Francesco , Russo Andrea , Semeraro Francesco 
Published: February 2021

Purpose:
To compare sensitivity of the retina after complete internal limiting membrane (ILM) peeling versus foveal-sparing ILM peeling in vitrectomy for vitreomacular traction syndrome.

Methods:
This was a randomized, prospective, comparative study. Thirty-four eyes were randomized to undergo peeling with foveal sparing of the ILM (FS group) or complete peeling group. Foveal and perifoveal retinal sensitivity, visual acuity, and central macular thickness were the main outcome measures.

Results:
Parafoveal retinal sensitivity exhibited a significant improvement in both the FS and complete peeling groups (+2.43 ± 0.82 dB and +1.79 ± 0.86 dB, respectively; P = 0.037). Significant improvements were observed in both visual acuity and central macular thickness in both groups. No cases of epiretinal membrane recurrence were observed in the FS group.

Conclusion:
Both the FS and complete peeling surgical techniques are safe and yielded good anatomical and functional results; however, a significant difference in favor of FS was found in relation to the best-corrected visual acuity and perifoveal retinal sensitivity. Preservation of the foveal ILM disc allowed the anatomical restoration of the foveal architecture in most vitreomacular traction syndrome cases without signs of stiffening or ILM fibrosis over a follow-up period of 1 year.
Multidisciplinary Management of Orbital Metastasis and Survival Outcomes
Authors: El-Hadad Christian , Koka Kirthi , Dong Wenli , Do Thai , Haider Maryam , Ursua Jocelyn D. , Ning Jing , Debnam James Matthew , Esmaeli Bita 
Published: February 2021

Purpose:
To study the multidisciplinary management and survival outcomes of orbital metastasis (OM).

Methods:
All patients with a diagnosis of OM treated during 1999–2019 were included. Clinical data were retrospectively collected and analyzed.

Results:
The study included 118 patients, 71 females and 47 males, with a median age of 61 years. The most common primary tumor types were breast carcinoma (43 patients), melanoma (17), and lung (13), thyroid (7), renal cell (6), and neuroendocrine carcinoma (6). Ninety-six patients had a known history of cancer at OM diagnosis. The median time from diagnosis of primary cancer to OM was 31 months (range, 0–304). In 22 patients, OM was the first sign of cancer. In 47 patients, the orbit was the only site of metastasis. The most common presenting features were restricted by extraocular motility (77 patients) and proptosis (61). Eight patients had enophthalmos. OM was diagnosed based on clinical history and imaging studies in 81 patients and orbital biopsy in 37. One hundred nine patients were treated with chemotherapy and immunotherapy, 75 with radiation, and 21 with palliative surgical resection. Eighty-two patients died during follow up. The median overall survival (OS) time after diagnosis of OM was 17 months (95% CI: 12–28). OM from renal cell carcinoma was associated with the best and OM from thyroid cancer with the worst OS. Patients with breast cancer had longer median survival (28 months; 95% CI: 15–60) than patients with lung, melanoma, neuroendocrine, or thyroid cancer.

Conclusion:
In this large series, breast cancer and melanoma were the most common causes of OM. Most patients had a known history of cancer at OM diagnosis and did not require orbital biopsy to confirm the diagnosis. Patients with renal cell carcinoma and breast carcinoma had the best prognosis after diagnosis of OM.
Conjunctival Actinic Granuloma: A Clinicopathological and Immunohistochemical Study With a Review of the Literature and a Differential Diagnosis
Authors: Neerukonda Vamsee , Jakobiec Frederick A. , Barrantes Paula Cortes , Campbell Douglas , Stagner Anna M. 
Published: February 2021

Purpose:
To document a case of actinic granuloma (AG) of the conjunctiva, provide an extensive histopathologic and immunohistochemical description, review previously reported cases, and supply a differential diagnosis.

Methods:
Both a retrospective chart review and comprehensive literature review were performed. The distinctive histopathologic pattern of the current case was defined with histochemical and immunohistochemical stains (CD163, p63, and a Verhoeff–Van Gieson elastic stain). Clinical follow up was obtained.

Results:
A granulomatous process composed of CD163-positive mononuclear epithelioid cells and multinucleated giant cells was characterized by displaced extracellular actinic-related elastic fibers to the base of the lesion. Small elastic fibers were phagocytosed in epithelioid cells. Pseudoepitheliomatous hyperplasia of the overlying squamous epithelium was present; p63 assisted in defining the squamous proliferation and highlighted its noninvasive nature. Conjunctival AGs, according to the literature review, occur almost exclusively in young females, clinically manifest as nodular foci with painless injection over the course of weeks, and histologically featured granulomatous inflammation and elastophagocytosis. The etiology of this entity is likely multifactorial, but its genesis revolves around actinic injury.

Conclusion:
AGs of the conjunctiva have likely been an underreported entity in the past. The authors’ review underscores the importance of including conjunctival AGs in the differential diagnosis of painless, subacute injected masses of the perilimbal conjunctiva. While it is benign, histopathologically separating AGs from neoplasia and other mimickers such pinguecula, foreign body granulomas, allergic, or rheumatoid nodules is essential for optimal management.
Clinical Pathway for Vaso-Occlusive Pain Reduces Hospital Admissions
Authors: Jones Wallace , Jang Albert , Myers Leann , Dasgupta Aditi , DeBord Jessica 
Published: February 2021

ABSTRACT

Background:
Vaso-occlusive pain leads to high acute care utilization among patients with sickle cell disease (SCD). Data suggest that clinical pathways (CPWs) reduce variation in the management of vaso-occlusive pain and improve clinical outcomes.

Methods:
We implemented and evaluated a CPW for vaso-occlusive pain at our institution using a before and after study design. The primary objective was to decrease acute care utilization among patients with SCD, which was assessed by the primary outcome measures of hospital length of stay (LOS), 30-day readmission rate, and total hospitalizations annually per patient. Secondary outcome measures were packed red blood cell transfusions, and acute chest syndrome incidence. Patient-controlled analgesia use and promethazine use were assessed to estimate CPW use.

Results:
Three hundred fourty-four admissions in 112 patients were analyzed, of which 193 admissions occurred pre-CPW and 151 admissions occurred post-CPW implementation. Post-CPW implementation, we observed a significant decrease in hospital admissions annually per patient, an increase in patient-controlled analgesia use, and a decrease in intravenous promethazine use. We observed trends toward decreased 30-day readmission rate and increased acute chest syndrome incidence, which were not statistically significant. No effect was found on hospital LOS.

Conclusions:
Clinical pathway implementation at our institution reduced variation in management and decreased hospital admissions for vaso-occlusive pain.
A Review of Chronic Comorbidities in Adults Living With HIV: State of the Science
Authors: Webel Allison R. , Schexnayder Julie , Cioe Patricia A. , Zuñiga Julie A. 
Published: February 2021

Abstract
People living with HIV are living longer, high-quality lives; however, as they age, this population is at increased risk for developing chronic comorbidities, including cardiovascular disease, certain types of cancer (e.g., lung, anal, and liver), and diabetes mellitus. The purpose of this state-of-the-science review is to provide an evidence-based summary on common physical comorbidities experienced by people living and aging with HIV. We focus on those chronic conditions that are prevalent and growing and share behavioral risk factors that are common in people living with HIV. We will discuss the current evidence on the epidemiology, physiology, prevention strategies, screening, and treatment options for people living with HIV across resource settings.
Iodine supplementation: is there a need?
Authors: Ley Delphine , Turck Dominique 
Published: February 2021

Purpose of review
To review the recent data on iodine deficiency, the impact of iodine deficiency on health outcomes and the need for iodine supplementation in at-risk populations, that is, pregnant and lactating women, infants and young children.

Recent findings
The 2019 Iodine Global Network Annual Report highlighted that only 23 countries worldwide (including Finland, Germany, and Norway in Europe) were classified as having insufficient iodine intake in 2019, down from 54 in 2003 and 113 in 1993. Even if severe iodine deficiency during pregnancy has a negative impact on cognitive outcomes later in life, the consequences of mild-to-moderate iodine deficiency on child neurodevelopment are controversial. Two 2017 and 2019 Cochrane Systematic Reviews found no evidence that iodine supplementation in women before, during or after pregnancy improved infant and child cognitive development in areas with mild-to-moderate iodine deficiency. Likewise, a 2019 Cochrane systematic review concluded that there was no evidence of a positive impact of iodine supplementation on morbidity, including cognitive impairment, and mortality in preterm infants.

Summary
There is no scientific evidence to support generalized iodine supplementation in mildly to moderately deficient settings not only in pregnant and lactating women but also in infants, either preterm or term, and in young children.