bluuebunny/crossref_metadata_2025 huggingface dataset:
Mission Accomplished
Authors: O'Driscoll Cian
Published: November 2019

The penultimate problem that just war theorists find with victory pertains to the contingencies of modern warfare. Insofar as today’s wars are configured in such a way that they are fundamentally ‘unwinnable’, it would be anachronistic to address them in the idiom of victory. This chapter assesses this contention. It confirms that, to the degree that victory is understood through the prism of so-called ‘decisive battles’, which is the standard way it has historically been conceived, there is a sound historical basis for declaiming victory as an obsolete concept. While this is true, it is not, however, the entire story. It overlooks the moral weight that this idealized vision of victory carries today, and indeed has always carried. Reflecting on this insight, this chapter concludes that what the examination of the relevance of victory to modern war reveals is the dated conception of war that underpins just war thinking.
Birth and Natality in Feminist Philosophy
Authors: Stone Alison
Published: November 2019

This chapter sets out the views on birth and being born of Irigaray, Cavarero, and Jantzen. Irigaray’s feminism of sexual difference and her attention to the maternal body lead her to consider birth. She argues that we have psychological difficulties around birth, difficulties that have found expression in canonical works of philosophy. For Irigaray, these expressions help us to piece together what is in fact involved in being born, and to remember our debts to the mothers from whom we are born. The chapter also looks at Cavarero’s understanding of natality, which is informed by Arendt as well as Irigaray, and at how Irigaray, Cavarero, and Jantzen criticize Western culture for being preoccupied with death and mortality while neglecting birth and natality.
Birth Anxieties
Authors: Stone Alison
Published: November 2019

This chapter looks at some forms and sources of birth anxiety. Our beginnings are mysterious to us, and because of infantile amnesia we can remember neither being born nor our formative years, which leaves much of our own personalities and motivations opaque to us. The chapter incorporates psychoanalytic insights into birth anxiety provided by Rank and Freud, and interprets separation anxiety as an anxiety that we suffer because of our natality. It also shows that Sartre’s and Kierkegaard’s existentialist views of anxiety leave room for certain kinds of birth anxiety. One is anxiety that we cannot honour all the obligations that come from the attachments we have inherited from birth; another is anxiety to be caught up in the wrongs of the society around us where, having been born, we are deeply shaped by these wrongs and cannot readily extricate ourselves from them.
States
Authors: Nicholson Rowan
Published: November 2019

This chapter concerns the general rules about statehood. The debate about statehood is traditionally conducted between adherents of the ‘declaratory’ theory, who say that it depends on criteria of effectiveness such as government, population, territory, and independence, and adherents of the ‘constitutive’ theory’, who argue that it depends on recognition by other states. The chapter raises doubts about both these approaches in their pure forms. It argues instead that there are two coexisting, alternative rules about statehood. An entity that meets effectiveness criteria is generally a state (the effectiveness norm). Equally, an entity that is recognized by other states, even if not effective, generally has the attributes of a state relative to recognizing states (the recognition norm). If an ineffective entity is recognized by some but not all other states, it may be described as a ‘state-in-context’; but if the entity is recognized universally, for legal purposes it may be considered a state without qualification.
States
Authors: Nicholson Rowan
Published: November 2019

The purpose of this chapter is to identify exceptions to the general rules discussed in the previous chapter (the effectiveness and recognition norms). Among the exceptions that are identified is an exception to the recognition norm that partly aligns it with the effectiveness norm: a unilateral secessionist entity cannot be recognized in derogation from an existing state’s territorial integrity. There are other exceptions based on the principle that no law arises from unlawfulness (ex iniuria ius non oritur). The chapter also discusses the role of self-determination and postulates an exception to the exceptions: a right to external self-determination may enable states to emerge in circumstances that would otherwise render their creation invalid.
Hypertonic external medium represses cellular respiration and promotes Warburg/Crabtree effect
Authors: Hamraz Minoo , Abolhassani Raymond , Andriamihaja Mireille , Ransy Céline , Lenoir Véronique , Schwartz Laurent , Bouillaud Frédéric
Published: November 2019

Hyperosmotic conditions are associated to several pathological states. In this article, we evaluate the consequence of hyperosmotic medium on cellular energy metabolism. We demonstrate that exposure of cells to hyperosmotic conditions immediately reduces the mitochondrial oxidative phosphorylation rate. This causes an increase in glycolysis, which represses further respiration. This is known as the Warburg or Crabtree effect. In addition to aerobic glycolysis, we observed two other cellular responses that would help to preserve cellular ATP level and viability: A reduction in the cellular ATP turnover rate and a partial mitochondrial uncoupling which is expected to enhance ATP production by Krebs cycle. The latter is likely to constitute another metabolic adaptation to compensate for deficient oxidative phosphorylation that, importantly, is not dependent on glucose.
TRPV4 receptor as a functional sensory molecule in bladder urothelium: Stretch‐independent, tissue‐specific actions and pathological implications
Authors: Roberts Max W. G. , Sui Guiping , Wu Rui , Rong Weifang , Wildman Scott , Montgomery Bruce , Ali Ahmed , Langley Steve , Ruggieri Michael R. , Wu Changhao
Published: November 2019

The newly recognized sensory role of bladder urothelium has generated intense interest in identifying its novel sensory molecules. Sensory receptor TRPV4 may serve such function. However, specific and physiologically relevant tissue actions of TRPV4, stretch‐independent responses, and underlying mechanisms are unknown and its role in human conditions has not been examined. Here we showed TRPV4 expression in guinea‐pig urothelium, suburothelium, and bladder smooth muscle, with urothelial predominance. Selective TRPV4 activation without stretch evoked significant ATP release—key urothelial sensory process, from live mucosa tissue, full‐thickness bladder but not smooth muscle, and sustained muscle contractions. ATP release was mediated by Ca2+‐dependent, pannexin/connexin‐conductive pathway involving protein tyrosine kinase, but independent from vesicular transport and chloride channels. TRPV4 activation generated greater Ca2+ rise than purinergic activation in urothelial cells. There was intrinsic TRPV4 activity without exogeneous stimulus, causing ATP release. TRPV4 contributed to 50% stretch‐induced ATP release. TRPV4 activation also triggered superoxide release. TRPV4 expression was increased with aging. Human bladder mucosa presented similarities to guinea pigs. Overactive bladders exhibited greater TRPV4‐induced ATP release with age dependence. These data provide the first evidence in humans for the key functional role of TRPV4 in urothelium with specific mechanisms and identify TRPV4 up‐regulation in aging and overactive bladders.
Consensus and Controversies Between Pain and Addiction Experts on the Prevention, Diagnosis, and Management of Prescription Opioid Use Disorder
Authors: Kraus Mark , Lintzeris Nicholas , Bhaskar Arun , Alho Hannu , Alon Eli , Bouhassira Didier , Haro Gonzalo , D’Agnone Oscar , Dematteis Maurice , Kern Kai-Uwe , Maremmani Icro , Perrot Serge , Sittl Reinhard , Pellicano Kaitlin
Published: November 2019

Objectives:

Prescription opioid use disorder (POUD) is an established public health crisis in many countries, and current evidence indicates it is a growing problem in Europe. Many specialists play a role, including pain and addiction medicine specialists, in the diagnosis and management of POUD, but neither group can fully address these patients’ needs alone. The purpose of this consensus process was to bring together experts from pain and addiction medicine to examine the positions of both specialties.

Methods:

In all, 13 international pain medicine, addiction medicine, and addiction psychiatry experts convened a meeting to formulate a set of consensus statements on the diagnosis and management of POUD. The statements were further refined by a wider group of 22 European expert clinicians. At a second meeting of all 35 participants, a set of controversy statements was also developed to recognize some of the key areas of divergent opinion.

Results/conclusions:

There was a high level of agreement between pain and addiction specialists. Key themes that emerged were the need to strengthen interdisciplinary communication, a desire for greater education and training for clinicians in both specialties, and mutual acknowledgment of the importance of multidisciplinary management of POUD. The blurred line between poorly managed pain and POUD was also a subject of much discussion, reflecting the difficulties in defining and diagnosing this complex condition.
Vital Signs Monitoring with Wearable Sensors in High-risk Surgical Patients
Authors: Breteler Martine J. M. , KleinJan Eline J. , Dohmen Daan A. J. , Leenen Luke P. H. , van Hillegersberg Richard , Ruurda Jelle P. , van Loon Kim , Blokhuis Taco J. , Kalkman Cor J.
Published: November 2019

Background

Vital signs are usually recorded once every 8 h in patients at the hospital ward. Early signs of deterioration may therefore be missed. Wireless sensors have been developed that may capture patient deterioration earlier. The objective of this study was to determine whether two wearable patch sensors (SensiumVitals [Sensium Healthcare Ltd., United Kingdom] and HealthPatch [VitalConnect, USA]), a bed-based system (EarlySense [EarlySense Ltd., Israel]), and a patient-worn monitor (Masimo Radius-7 [Masimo Corporation, USA]) can reliably measure heart rate (HR) and respiratory rate (RR) continuously in patients recovering from major surgery.

Methods

In an observational method comparison study, HR and RR of high-risk surgical patients admitted to a step-down unit were simultaneously recorded with the devices under test and compared with an intensive care unit–grade monitoring system (XPREZZON [Spacelabs Healthcare, USA]) until transition to the ward. Outcome measures were 95% limits of agreement and bias. Clarke Error Grid analysis was performed to assess the ability to assist with correct treatment decisions. In addition, data loss and duration of data gaps were analyzed.

Results

Twenty-five high-risk surgical patients were included. More than 700 h of data were available for analysis. For HR, bias and limits of agreement were 1.0 (–6.3, 8.4), 1.3 (–0.5, 3.3), –1.4 (–5.1, 2.3), and –0.4 (–4.0, 3.1) for SensiumVitals, HealthPatch, EarlySense, and Masimo, respectively. For RR, these values were –0.8 (–7.4, 5.6), 0.4 (–3.9, 4.7), and 0.2 (–4.7, 4.4) respectively. HealthPatch overestimated RR, with a bias of 4.4 (limits: –4.4 to 13.3) breaths/minute. Data loss from wireless transmission varied from 13% (83 of 633 h) to 34% (122 of 360 h) for RR and 6% (47 of 727 h) to 27% (182 of 664 h) for HR.

Conclusions

All sensors were highly accurate for HR. For RR, the EarlySense, SensiumVitals sensor, and Masimo Radius-7 were reasonably accurate for RR. The accuracy for RR of the HealthPatch sensor was outside acceptable limits. Trend monitoring with wearable sensors could be valuable to timely detect patient deterioration.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Electrocardiographic Effects of Propofol versus Etomidate in Patients with Brugada Syndrome
Authors: Flamée Panagiotis , Varnavas Varnavas , Dewals Wendy , Carvalho Hugo , Cools Wilfried , Bhutia Jigme Tshering , Beckers Stefan , Umbrain Vincent , Verborgh Christian , Forget Patrice , Chierchia Gian-Battista , Brugada Pedro , Poelaert Jan , de Asmundis Carlo
Published: November 2019

Background

Brugada Syndrome is an inherited arrhythmogenic disease, characterized by the typical coved type ST-segment elevation in the right precordial leads from V1 through V3. The BrugadaDrugs.org Advisory Board recommends avoiding administration of propofol in patients with Brugada Syndrome. Since prospective studies are lacking, it was the purpose of this study to assess the electrocardiographic effects of propofol and etomidate on the ST- and QRS-segments. In this trial, it was hypothesized that administration of propofol or etomidate in bolus for induction of anesthesia, in patients with Brugada Syndrome, do not clinically affect the ST- and QRS-segments and do not induce arrhythmias.

Methods

In this prospective, double-blinded trial, 98 patients with established Brugada syndrome were randomized to receive propofol (2 to 3 mg/kg-1) or etomidate (0.2 to 0.3 mg/kg-1) for induction of anesthesia. The primary endpoints were the changes of the ST- and QRS-segment, and the occurrence of new arrhythmias upon induction of anesthesia.

Results

The analysis included 80 patients: 43 were administered propofol and 37 etomidate. None of the patients had a ST elevation greater than or equal to 0.2 mV, one in each group had a ST elevation of 0.15 mV. An ST depression up to −0.15mV was observed eleven times with propofol and five with etomidate. A QRS-prolongation of 25% upon induction was seen in one patient with propofol and three with etomidate. This trial failed to establish any evidence to suggest that changes in either group differed, with most percentiles being zero (median [25th, 75th], 0 [0, 0] vs. 0 [0, 0]). Finally, no new arrhythmias occurred perioperatively in both groups.

Conclusions

In this trial, there does not appear to be a significant difference in electrocardiographic changes in patients with Brugada syndrome when propofol versus etomidate were administered for induction of anesthesia. This study did not investigate electrocardiographic changes related to propofol used as an infusion for maintenance of anesthesia, so future studies would be warranted before conclusions about safety of propofol infusions in patients with Brugada syndrome can be determined.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Spinal fusion in children with osteogenesis imperfecta: A nationwide retrospective comparative cohort study over a 12-year period
Authors: Belyea Christopher M. , Knox Jeffrey B.
Published: November 2019

Background:

Osteogenesis imperfecta (OI) is an uncommon disorder frequently associated with spinal deformity. Relatively little is known about the effect this disorder has on the outcomes of spinal fusion for spinal deformity. The purpose of this study was to evaluate the differences in treatment and outcomes of this unique patient population.

Methods:

The nationwide HCUP Kids’ Inpatient Database (KID) from 2000 to 2012 was queried to identify patients with OI who underwent spinal fusion surgery for treatment of scoliosis. Demographic variables were obtained along with length of stay, mortality, length of fusion, transfusion rates, and hospital charges. Control data consisting of pediatric patients who underwent spinal fusion for adolescent idiopathic scoliosis (AIS) were acquired and compared.

Results:

A total of 60 patients (average age of 13.2 yr) with OI underwent spinal fusion during the study period. Of the patients who underwent fusions, 63.3% had involvement of nine or more vertebrae, which was significantly higher than patients with AIS (35.7%: P<0.001). Patients with OI also had a higher average length of stay (8.1 vs. 5.7 days: P<0.001). Nearly half of the patients with OI required blood transfusions, which was significantly more than patients with AIS (43.3% vs. 30.4%; P=0.029). Patients with OI also experienced significantly higher hospital charges versus controls ($173,652 vs. $46,953; P<0.0001).

Conclusions:

Spinal deformity surgery in patients with OI is a technically demanding procedure with high morbidity and high cost. In this nationwide series, a higher rate of blood transfusions, longer hospital stays, and significantly higher hospital charges were identified compared to patients with AIS.

Level of Evidence:

Level III, Retrospective comparative cohort study
Venous thromboembolism following foot and ankle surgery: A case series of two tertiary medical centers and a review of the literature
Authors: Arafah Orfan , Aldawsari Khalifah , Alsubaie Mohammed , Alshehri Khaled , Sayed Albaraa
Published: November 2019

Venous thromboembolism (VTE) is a serious medical concern after surgical interventions. The overall incidence of clinically symptomatic VTE after foot and ankle surgery is considered to be low. However, there are limited data on the actual incidence of symptomatic VTE after foot and ankle surgery especially in our region. The purpose of this study was to determine the incidence of clinically symptomatic VTE after foot and ankle surgery in two tertiary medical centers and to review the most recent literature on VTE incidence, risk factors, and prophylaxis after foot and ankle surgery. This study is divided into two parts: a retrospective case series and a review of the literature from 2017 to 2018. A retrospective review was performed of patients who underwent foot or ankle surgery in two tertiary medical centers in Riyadh, Saudi Arabia for 3 consecutive years. Patients 18 yr of age and older were included. The patients’ demographic data (age, gender, body mass index [BMI]), medical comorbidities (diabetes mellitus [DM] and hypertension [HTN]), type of procedure, and the use of prophylaxis were obtained from the medical records. The incidence of clinically symptomatic VTE was determined based on the 90-days follow-up and/or the radiographic report. All of the information was then confirmed by calling patients on the phone. Data were entered and analyzed. Out of 125 patients, 69 (55.2%) were female and 56 (44.8%) were male. Patients had a mean age of 38.7 yr and a BMI of 28.11 kg/m2. The incidence of clinically symptomatic VTE was 0.8% (one out of 125), diagnosed in a 39-year-old male who was medically cleared and not on prophylaxis. Symptomatic deep vein thrombosis was confirmed by the radiographic report. The incidence of symptomatic VTE after foot and ankle surgery appeared to be low (less than 1%). The decision to prescribe thromboprophylaxis should be based on individual factors and characteristics.

Level of Evidence:

Level IV.
Acute Implant-related Complications in Pediatric Cervical Spine Fusion
Authors: O’Neill Nora P. , Hresko Michael T. , Emans John B. , Glotzbecker Michael P. , Verhofste Bram P. , Karlin Lawrence I. , Proctor Mark R. , Hedequist Daniel J.
Published: November 2019

Background:

The use of modern rigid instrumentation in pediatric cervical fusions decreases the risk of implant-related complications, both acute and long term. However, previous studies have indicated that acute implant-related issues still occur in the adult population. Reports of pediatric acute implant complications, occurring within 3 months of surgery, are under-represented in the literature. The purpose of this study is to document the prevalence of acute implant-related complications in a pediatric cervical fusion population.

Methods:

A retrospective review of instrumented cervical fusions from August 2002 to December 2018 was conducted. Acute implant-related complications were defined as malposition, fracture, or disengagement of cervical instrumentation, including screws, rods, and plates, within 90 days of surgery.

Results:

A total of 166 cases were included (55% male individuals) with an average age at surgery of 12.5 years (SD, ±5.28). Acute implant-related complications occurred in 5 patients (3%). All 5 patients had a syndromic diagnosis: Loeys-Dietz (n=1), osteopetrosis (n=1), neurofibromatosis (n=1), trisomy 20 (n=1), and achondroplasia (n=1). One case involved asymptomatic screw protrusion, 1 case lateral mass screw pull-out, 2 more had screw-rod disengagement, and the last experienced dislodgement of the anterior plate. The median time until the presentation was 25 days (range, 1 to 79 d). All patients (n=5) required surgical revision.

Conclusions:

This case series suggests that the overall incidence of acute cervical implant failure is low. However, failure is more likely to occur in patients with underlying syndromes compared with patients with different etiologies. Intraoperative use of 3-dimensional computed tomography imaging is recommended to evaluate the screw position and potentially avoid later surgery.
Evaluation of Risk Factors for Cerebrospinal Leakage in Pediatric Patients With Cerebral Palsy Treated With Intrathecal Baclofen
Authors: Imerci Ahmet , Rogers Kenneth J. , Miller Freeman , Sees Julieanne P.
Published: November 2019

Background:

Insertion of an intrathecal baclofen (ITB) pump can provide significant benefits in patients with cerebral palsy (CP). However, there are little data describing the risk of complications. Specifically, there is a lack of data describing the incidence of cerebrospinal fluid (CSF) leakage and risk factors following ITB placement. The purpose of our study was to describe risk factors for developing CSF leak in pediatric patients with CP treated with ITB and to report the treatment and outcome of CSF leaks.

Methods:

Following institutional review board approval, 720 ITB procedures in 341 children with CP were identified retrospectively over a 15-year study period. Patients’ demographic characteristics, medical comorbidities, muscle tone patterns, feeding tube status, seizure history, inpatient events, ITB-related CSF leak and headache complaints and their management, and other complications were evaluated.

Results:

Eighty-five (24.9%) patients experienced 90 CSF leak episodes over a follow-up time of 6.3±3.9 years. There were 72 episodes of headache as a result of CSF leakage in 61 (71.7%) of these 85 patients. There was a positive correlation between the risk of CSF leak and preoperative comorbidities such as epilepsy/seizure history, feeding tube, mixed type CP, and dystonic type CP. The risk of CSF leak after primary ITB administration was 5.8% (20/341), and the risk after secondary ITB procedures due to complications was 24.2% (32/132). There was no significant relationship between CSF leak and primary ITB (P=0.21), but the risk of CSF leak was positively correlated to the secondary ITB due to complications (P<0.05).

Conclusions:

CSF leak was fairly common (25% incidence), and it correlated with epilepsy/seizure history, feeding tube, mixed type CP, and dystonic type CP. Recurrent ITB procedures were a risk factor for CSF leak. Half of these patients had self-limited symptoms that improved with conservative medical treatment, and the epidural blood patch was successful in resistant cases. Successful treatment of CSF leakage complications allows patients to continue ITB.

Level of Evidence:

Level III.
Effect of miR-196a inhibition on esophageal cancer growth in vitro
Authors: Bai Minghua , Dong Yiping , Zhou Congya , Sun Xiao , Ma Jinlu , Han Suxia
Published: November 2019

Esophageal cancer has recent shown a higher incidence but lower 5-year survival rate after normal clinical treatment in China. The aim of this study was to observe whether the inhibition of miR-196a affects esophageal cancer cell growth by modulating the nuclear factor-κB target gene and to detect the possible cooperative therapeutic effects on esophageal cancer by knocking down miR-196a expression combined with the specific inhibitor of nuclear factor-κB target genes. Thus, anti-miR-196a or sotrastaurin, a protein kinase C (PKC) inhibitor, were used to alter PKC expression. We found that miR-196a knockdown or PKC inhibition by sotrastaurin changed PKC expression which then reduced esophageal cancer cell proliferation and downregulated proliferating cell nuclear antigen expression via the classical B-cell receptor-PKC nuclear factor-κB pathway but not the alternative pathway; in addition, miR-196a inhibition can increase the caspase level and induce esophageal cancer cell apoptosis. Our current results provided the evidence that miR-196a was related to the classical nuclear factor-κB pathway, and these new findings proved the potential therapeutic effect of miR-196a in targeted therapy for clinical esophageal cancer patients.
Neuroprognostication Practices in Postcardiac Arrest Patients: An International Survey of Critical Care Providers
Authors: Maciel Carolina B. , Barden Mary M. , Youn Teddy S. , Dhakar Monica B. , Greer David M.
Published: November 2019

Objectives:

To characterize approaches to neurologic outcome prediction by practitioners who assess prognosis in unconscious cardiac arrest individuals, and assess compliance to available guidelines.

Design:

International cross-sectional study.

Setting:

We administered a web-based survey to members of Neurocritical Care Society, Society of Critical Care Medicine, and American Academy of Neurology who manage unconscious cardiac arrest patients to characterize practitioner demographics and current neuroprognostic practice patterns.

Subjects:

Physicians that are members of aforementioned societies who care for successfully resuscitated cardiac arrest individuals.

Interventions:

Not applicable.

Measurements and Main Results:

A total of 762 physicians from 22 countries responses were obtained. A significant proportion of respondents used absent corneal reflexes (33.5%) and absent pupillary reflexes (36.2%) at 24 hours, which is earlier than the recommended 72 hours in the standard guidelines. Certain components of the neurologic examination may be overvalued, such as absent motor response or extensor posturing, which 87% of respondents considered being very or critically important prognostic indicators. Respondents continue to rely on myoclonic status epilepticus and neuroimaging, which were favored over median nerve somatosensory evoked potentials for prognostication, although the latter has been demonstrated to have a higher predictive value. Regarding definitive recommendations based on poor neurologic prognosis, most physicians seem to wait until the postarrest timepoints proposed by current guidelines, but up to 25% use premature time windows.

Conclusions:

Neuroprognostic approaches to hypoxic-ischemic encephalopathy vary among physicians and are often not consistent with current guidelines. The overall inconsistency in approaches and deviation from evidence-based recommendations are concerning in this disease state where mortality is so integrally related to outcome prediction.
Effect of Best Practice Advisories on Sedation Protocol Compliance and Drug-Related Hazardous Condition Mitigation Among Critical Care Patients*
Authors: Greene Rebecca A. , Zullo Andrew R. , Mailloux Craig M. , Berard-Collins Christine , Levy Mitchell M. , Amass Timothy
Published: November 2019

Objectives:

To determine whether best practice advisories improved sedation protocol compliance and could mitigate potential propofol-related hazardous conditions.

Design:

Retrospective observational cohort study.

Setting:

Two adult ICUs at two academic medical centers that share the same sedation protocol.

Patients:

Adults 18 years old or older admitted to the ICU between January 1, 2016, and January 31, 2018, who received a continuous infusion of propofol.

Interventions:

Two concurrent best practice advisories built in the electronic health record as a clinical decision support tool to enforce protocol compliance with triglyceride and lipase level monitoring and mitigate propofol-related hazardous conditions.

Measurements and Main Results:

The primary outcomes were baseline and day 3 compliance with triglyceride and lipase laboratory monitoring per protocol and time to discontinuation of propofol in the setting of triglyceride and/or lipase levels exceeding protocol cutoffs. A total of 1,394 patients were included in the study cohort (n = 700 in the pre–best practice advisory group; n = 694 in the post–best practice advisory group). In inverse probability weighted regression analyses, implementing the best practice advisory was associated with a 56.6% (95% CI, 52.6–60.9) absolute increase and a 173% relative increase (risk ratio, 2.73; 95% CI, 2.45–3.04) in baseline laboratory monitoring. The best practice advisory was associated with a 34.0% (95% CI, 20.9–47.1) absolute increase and a 74% (95% CI, 1.39–2.19) relative increase in day 3 laboratory monitoring after inverse probability weighted analyses. Among patients with laboratory values exceeding protocol cutoffs, implementation of the best practice advisory resulted in providers discontinuing propofol an average of 16.6 hours (95% CI, 4.8–28.3) sooner than pre–best practice advisory. Findings from alternate analyses using interrupted time series were consistent with the inverse probability weighted analyses.

Conclusions:

Best practice advisories can be effectively used in ICUs to improve sedation protocol compliance and may mitigate potential propofol-related hazardous conditions. Best practice advisories should undergo continuous quality assurance and optimizations to maximize clinical utility and minimize alert fatigue.
Intraepidermal Nerve Fiber Density in Postmortem Skin: A Novel Approach
Authors: Waheed Waqar , Taicher Christopher , Dulaney Eugene , Eckenstein Felix , Hehir Michael , Sprague Julian , Tandan Rup
Published: November 2019

Objective:

To determine the feasibility of examining intraepidermal nerve fiber density (IENFD) in postmortem skin.

Methods:

From 12 subjects, 3-mm skin punch biopsies were collected 1–4 days postmortem from the proximal leg and distal leg, with a mean (range) interval from the death of 37 (15–91) hours. Causes of death varied broadly, including hepatocellular carcinoma, chronic lymphocytic leukemia, generalized atherosclerosis, progressive supranuclear palsy, Parkinson disease, emphysema, and obesity. The mean (range) number of sections evaluated from each biopsy was 5.08 (2–6) from the proximal leg and 5.92 (5–6) from the distal leg. Sections were stained with PGP 9.5 for blinded counting using bright field microscopy. Qualitative and quantitative assessment of feasibility included a comparison of fiber staining with that in healthy subjects and mean IENFD in postmortem samples. Interobserver reliability was assessed among 3 blinded raters by calculating intraclass correlation coefficients and percentage variability of IENFD in at least 4 sections from biopsies in 5 healthy subjects.

Results:

Intraobserver and interobserver correlation coefficients of blinded IENFD counts undertaken by 4 authors were consistently >0.80, and the coefficient of variation was ≤10%. The quality of staining in postmortem samples was comparable with that in healthy subjects and was not substantially affected by time from death to specimen collection of up to nearly 4 days. Mean (range) IENFD from postmortem samples in the proximal and distal leg was 2.73 (0–7.65) and 1.93 (0–4.91) fibers/mm of skin, respectively. Two of 3 patients who had received chemotherapy during life showed a nearly complete absence of intraepidermal nerve fibers.

Conclusions:

IENFD measurement in postmortem skin is feasible and may be used to study the epidemiology of SFN.
Evaluation of Quality of Life in Patients With Chronic Inflammatory Demyelinating Polyneuropathy in Iran
Authors: Okhovat Ali Asghar , Gholamalizadeh Saba , Nafissi Shahriar , Fatehi Farzad
Published: November 2019

Objectives:

In addition to the physical disability in chronic inflammatory demyelinating polyneuropathy (CIDP), various aspects of quality of life (QoL) are affected by the disease. Our goal was to evaluate the QoL in Iranian patients with CIDP and to study the association of clinical and demographic factors with QoL parameters.

Methods:

Twenty-six Iranian patients with CIDP were asked to complete a standardized Persian version of SF-36, and the association of demographic and functional parameters with QoL parameters was assessed.

Results:

Sex, living place, and income had no significant effect on QoL. Mean physical composite score was 37.7 ± 9.4, and mean mental composite score was 37.2 ± 15.2 that was lower than similar studies. There was a positive correlation between QoL and muscle strength of different muscle groups [hand (r = 0.41, P = 0.04); hip (r = 0.44, P = 0.02); and foot (r = 0.41, P = 0.04); total manual muscle testing (r = 0.46, P = 0.02)] and a significant negative correlation between the duration of illness and mean physical composite score (r = −0.61, P = 0.00).

Conclusions:

Our patients achieved low scores in both the physical and mental aspects of QoL compared with other studies. We found a significant correlation between the physical domain of the SF-36 score and muscle strength of the hand, hip, and foot muscle group and with total manual muscle testing, suggesting that physical disability is the most crucial factor affecting QoL. Also, there was a significant negative association between the duration of the disease and the physical domain.
Drug-Drug Interactions Between Antiretrovirals and Carbamazepine/Oxcarbazepine: A Real-Life Investigation
Authors: Cattaneo Dario , Baldelli Sara , Cozzi Valeria , Fusi Marta , Atzori Chiara , Micheli Valeria , Filice Carlo , Gervasoni Cristina
Published: November 2019

Background:

Carbamazepine and oxcarbazepine are potent modulators of metabolic enzymes. Hence, potential drug-drug interactions (DDIs) may occur between these 2 drugs and antiretrovirals. Here, we aimed to assess the relevance of these drug-drug interactions in real-life clinical settings.

Methods:

Patients treated concomitantly with carbamazepine or oxcarbazepine and antiretrovirals for at least 3 months were considered. Data on therapeutic drug monitoring (TDM) of both antiepileptic and antiretrovirals as trough concentrations were collected. HIV-infected patients not concomitantly treated with antiepileptic drugs and who underwent TDM for antiretrovirals in the previous 2 years were considered as controls.

Results:

Eleven HIV-positive patients prescribed carbamazepine or oxcarbazepine were identified. All the TDM evaluations for carbamazepine and oxcarbazepine that resulted were within the therapeutic ranges. TDM results of darunavir measured in these patients were comparable with values usually measured in the control group. Conversely, the trough concentrations for atazanavir and dolutegravir demonstrated significantly lower values when compared with values usually measured in HIV-infected patients not treated with antiepileptic drugs (190 ± 91 versus 546 ± 380 ng/mL; −65%, P < 0.001; 191 ± 78 versus 1096 ± 510 ng/mL; −83%, P < 0.001, respectively).

Conclusions:

Co-administration of carbamazepine or oxcarbazepine with atazanavir or dolutegravir should be avoided owing to the potential risk of virological failure; in case of these 2 drugs, the adoption of TDM is strongly advisable, eventually combining with increased antiretroviral doses.
Use of Essential Oils by Health Care Professionals for Health Maintenance
Authors: Childers Patricia M. , Aleshire Mollie E.
Published: November 2019

This study explores essential oils' use by health care professionals for health maintenance. A qualitative, descriptive design was employed, and a convenience sample of 10 participants was interviewed. Four themes were identified: an essential oils' community, essential oils' use, essential oils' acceptance, and essential oils' benefits and harms.
Intravenous Ketorolac Reduces Pain Score and Opioid Requirement in Orbital Surgery
Authors: Wladis Edward J. , Lee Katherine W. , De Arup
Published: November 2019

Purpose:

Intravenous ketorolac (IVK) is an effective agent to reduce postoperative pain without the risks inherent to opioid analgesics. However, many clinicians avoid using this agent due to concerns regarding hemorrhagic complications. This study was performed to assess the efficacy and safety of IVK in the setting of orbital surgery.

Methods:

In a single dose prospective study, patients either received IVK immediately before orbital surgery (n = 50) or acted as controls (n = 50). Postoperative pain was evaluated via a numerical scale (range = 0–10) immediately after surgery, before discharge to home, and on the first postoperative day (POD1). The requirements for opioid analgesic and anti-emetic medications were determined by the nursing staff and recorded. Statistical analyses were performed via a dedicated software package.

Results:

Fifty patients received IVK (24 males, 26 females, mean age = 54 years, SD = 18 years) and 50 patients acted as controls (26 males, 24 females, mean age = 50 years, SD = 19 years) immediately before orbital surgery. Mean pain scores were lower in patients who received IVK than in controls immediately after surgery (3.08 vs. 5.44, p = 0.0001) and on POD1 (1.04 vs. 2.66, respectively, p = 0.0001). Four patients (8%) who received IVK and 12 patients who did not (24%) required opioid analgesics to control pain (p = 0.03). No patient experienced a hemorrhagic complication or required an emergent return to the operating room.

Conclusions:

In the setting of orbital surgery, IVK safely and effectively reduces pain and the requirement for opioid analgesics. Within the limits of the study size, increased risks of bleeding-related complications were not identified.
Optic Nerve Stretch Is Unlikely to Be a Significant Causative Factor in Dysthyroid Optic Neuropathy
Authors: Rose Geoffrey E. , Vahdani Kaveh
Published: November 2019

Purpose:

Although it is a commonly held belief that stretching of the optic nerve is important in dysthyroid optic neuropathy (DON), it is probably mainly due to microvascular ischemia arising from high pressure at the orbital apex. If stretch is important in DON, one would expect longer optic nerves and reduced optic nerve compliance in these patients.

Methods:

Retrospective comparative case series for 75 patients with DON, and for age- and sex-matched control patients with thyroid eye disease (but no DON). Masked assessments of medial wall length, lateral wall length, optic nerve limits (ONLs), globe dimension, and globe projection were made from orbital CT images, and, from these measurements, various derivatives were estimated. The optic nerve shape was also judged as “straight,” “mildly curved,” or “markedly curved.” Estimates of optic nerve compliance were compared in the 2 groups and examined particularly to look for evidence of reduced compliance in orbits with DON.

Results:

Paired right–left comparisons suggested a small systematic bias in the estimates of orbital dimensions, possibly due to software performance; this does not complicate the study, as only ipsilateral orbits were compared in the 2 groups. In 115 paired orbits, there was no difference in the proportions with various optic nerve configuration (p = 1.0), but the mean ONL in DON was 32.9 mm, compared with 31.5 mm in thyroid eye disease without DON (p = 0.011). In 5 patients with bilateral thyroid eye disease but unilateral DON, when corrected for side-to-side bias, the ONL on the DON side was greater than the non-DON side (DON, 36.7 mm; non-DON, 34.7 mm; p = 0.066). Compliance estimates for the 115 paired orbits are almost identical (p = 0.99).

Conclusions:

The almost identical compliance estimates for DON and non-DON orbits suggest that ONL elongation in DON, albeit significant, is not extending optic nerve to its elastic limits and is, therefore, unlikely to be causing metabolic stress to the optic nerve. The 1.4 mm extra ONL in DON orbits probably just represents more retrobulbar tissues—with more advanced disease—and optic nerve stretch is probably not significant in the pathogenesis of DON.
Clinicopathologic Correlation of Kaposi Sarcoma Involving the Ocular Adnexa: Immunophenotyping of Diagnostic and Therapeutic Targets
Authors: Ulloa-Padilla Jan P. , Ghassibi Mark P. , Dubovy Sander R. , Kerr Darcy A.
Published: November 2019

Purpose:

To describe the clinicopathologic characteristics and the expression of diagnostic/treatment targets in ocular adnexal Kaposi Sarcoma.

Methods:

We conducted a clinical-pathologic retrospective case series. Immunohistochemical staining for cluster of differentiation 31 (CD31), human herpesvirus-8 (HHV8), platelet-derived growth factor receptor alpha (PDGFR-A), vascular endothelial growth factor receptor-1 (VEGF), tyrosine-protein kinase Kit (c-Kit), and programmed cell death protein 1 (PD-1) were performed. Percentage of positive tumor cells was recorded for PD-1; staining intensity and distribution (H-score) were determined for the remaining stains. A Friedman non-parametric ANOVA analysis evaluated the staining.

Results:

The study cohort included 13 patients (age 25 to 95 years; mean 46): 7 lesions were in the eyelid, 5 in the conjunctiva, and 1 in the cornea. Nine of 11 lesions (82%) were in human immunodeficiency syndrome-positive patients (human immunodeficiency syndrome status was unknown in 2 cases). Staging included 6 plaques and 7 nodules. The mean H-scores of CD31, HHV8, c-Kit, VEGF, and PDGF-A were 8.00, 8.23, 2.77, 11.54, and 10.31, respectively. Mean PD-1 staining was 6.46%. The Friedman non-parametric ANOVA analysis showed VEGF, PDGF-A, CD31, and HHV8 differed significantly, and all differed significantly from c-Kit. Programmed cell death protein 1 staining was not significant with any clinical variable.

Conclusions:

Cluster of differentiation 31 and HHV8 are helpful diagnostic adjuncts for ocular adnexal Kaposi Sarcoma. Platelet-derived growth factor receptor alpha and VEGF are promising treatment targets. Programmed cell death protein 1/PD-L1 and c-Kit are targets that are useful in several tumors; their roles in ocular adnexal Kaposi Sarcoma warrant further studies.
Corneal Laceration Associated With Upper Eyelid Blepharoplasty
Authors: Shoji Marissa K. , Tran Ann Q. , Nikpoor Neda , Lee Wendy W.
Published: November 2019

A 64-year-old woman underwent bilateral upper eyelid blepharoplasty and subsequently presented with decreased vision at her first postoperative visit 1 week later. She was found to have an 8-mm partial-thickness corneal laceration of her left eye and underwent immediate surgical laceration repair. The laceration etiology was thought to be related to damage from the initial blepharoplasty incision or Bovie cautery tip–induced laceration. After laceration repair, she had residual astigmatism and corneal scarring leading to poor vision. Corneal injuries, including abrasions and perforations, are rare complications of blepharoplasty, and the case in this study is the first report of corneal laceration following blepharoplasty. Corneal perforations and lacerations can lead to significant damage and vision loss, indicating a need for careful attention to surgical technique and instrument placement intraoperatively, routine use of corneal protectors even during superficial aesthetic procedures such as blepharoplasties, and comprehensive postoperative patient instructions.

A 64-year-old woman who underwent an upper eyelid blepharoplasty sustained a partial-thickness corneal laceration of her OS, which required emergent repair and resulted in persistent vision loss secondary to large corneal scar.
Secondary Acquired Nasolacrimal Duct Obstruction as a Specific Complication of Treatment With Radioactive Iodine (Morphological Study)
Authors: Fedorov Anatoly A. , Atkova Eugenia L. , Yartsev Vasily D.
Published: November 2019

Purpose:

To conduct a morphological study of structural changes in the nasolacrimal duct in secondary acquired nasolacrimal duct obstruction (SALDO) as a result of treatment with radioiodine.

Methods:

Twenty patients (20 cases) were involved: 10 cases with secondary acquired nasolacrimal duct obstruction at Hasner’s valve level due to the treatment with radioiodine (group 1) and 10 cases with primary acquired nasolacrimal duct obstruction (group 2). During surgery, a biopsy of nasolacrimal duct tissue from Hasner’s valve area was taken. A morphological study was performed using semi-fine sections technique.

Results:

Patients of group 1 showed the following: desquamation of columnar epithelium, pinpoint ulceration of nasolacrimal duct wall, collapse of a significant part of the capillary bed, and absence of blood cells in their lumen. State of secretory cells of mucous glands varied from necrobiotic to the different stages of dystrophic, decreased lumens of acini with abundant microvesicles in cell cytoplasm were revealed. A specific sign noted in patients of group 2 was mixed inflammatory infiltration of the mucosa of the nasolacrimal duct. The picture corresponds to the exacerbation of a chronic inflammatory process.

Conclusions:

Changes revealed in patients of group 1 include desquamation of nasolacrimal duct epithelium, mucous gland lesion, and moderate fibrosis that indicate a probable primary character of the lesion. In patients of group 2, fibrotic changes were more significant and were due to a chronic inflammatory process. Thus, secondary acquired nasolacrimal duct obstruction after treatment with radioactive iodine has a specific pathogenesis and should be classified as a separate nosological form.
Submental and Anterior Neck Originated Full-Thickness Skin Grafts for Periocular Procedures
Authors: Ben Artsi Elad , Ullrich Katja , Malhotra Raman
Published: November 2019

Purpose:

The submental and neck regions share cutaneous features with the face and are suitable donor sites for facial full-thickness skin grafts (FTSGs). Age-related laxity and skin redundancy in the cervicomental region may be an additional motivator to use its skin. We aim to describe, raise awareness, and remind surgeons of the utilization of submental and anterior neck as sources of FTSG for the periocular region, particularly when traditional donor sites are unavailable.

Methods:

Retrospective case series of 5 patients who underwent periocular FTSG from anterior neck and submental regions between January 2017 and January 2019. All patients had contraindications to the usually preferred graft donor sites. Main outcome measures were surgical functional results and cosmesis.

Results:

Five patients (all female) received FTSGs using anterior neck and submental regions as donor sites. Two patients required skin grafts due to eyelid retraction and anterior lamella shortening; one due to previous multiple basal cell carcinoma excisions with FTSG reconstructions and the other due to chronic Bell’s palsy. Three patients required skin grafts for Hughes flap reconstruction after excision of lower eyelid basal cell carcinoma. In all patients, conventional skin donor sites were unavailable or unsuitable due to previous skin grafting, actinic changes, postauricular situated hearing aids or patient’s preference. All patients achieved good cosmesis and functional results. None of the patients experienced donor site morbidities.

Conclusions:

Submental and anterior neck regions are useful FTSG donor sites for periocular procedures, particularly in elderly female patients with submental fullness and neck skin redundancy.