bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Use Cognitively Diagnostic Assessments of Student Performance as a Method for Monitoring and Managing the Instructional Quality in Undergraduate Medical Education
Authors: Bangeranye Catherine , Lim Youn Seon
Published: August 2019

Purpose

Course evaluations by students are a standard tool that U.S. universities use to monitor the quality of their product. Here, the authors examine an alternative method of monitoring instructional quality that differs from traditional approaches in that it does not rely on students’ ratings. The authors sought to glean relevant diagnostic information about course effectiveness from in-class exams used to assess students’ learning progress (i.e., cognitively diagnostic assessments that explicitly target instructional content).

Method

The authors used data from an end-of-course, cumulative exam given in 2015 and in 2016 to 200 first-year medical students. They mapped the exam questions to 4 attributes and analyzed the students’ overall mastery of the content tested and the percentage of students mastering each attribute.

Results

Analyses of the cognitively diagnostic assessment data revealed the percentage of the cohort who achieved/failed to achieve mastery of each of the attributes, discreet mastery profiles that distinguish among students with similar scores, and the percentage of the cohort within each of the 16 attribute mastery profiles. Analysis allowed the authors to evaluate how well the course content was delivered.

Conclusions

Cognitively diagnostic assessments enable in-class tests to appraise which skills specified in the curriculum have/have not been mastered by the students and how many students have mastered/failed to master which particular skills. Hence, if the learning goals have been well defined at the beginning of a course, then cognitively diagnostic assessments can show to what degree the instructional objectives have actually been accomplished.
The Covenant
Authors: Ofri Danielle
Published: August 2019

Burnout among doctors appears to be at epidemic proportions these days, with concomitant gushing prescriptions for wellness and resilience. But in reality, most doctors are not burned out in the traditional sense of the word: Most love taking care of patients and want nothing more than to be able to do just that. The source of the agony is the profession—or rather the corporatization of the profession—that has so impinged upon doctors’ ability to practice medicine. Doctors placed their trust in the medical profession, but that trust has been roundly trounced. So, rather than prescribe Pilates classes for overstressed doctors, it is time for the medical profession—and the health care industry that has subsumed it—to get a checkup.
Pharmacodynamic Interaction of Remifentanil and Dexmedetomidine on Depth of Sedation and Tolerance of Laryngoscopy
Authors: Weerink Maud A. S. , Barends Clemens R. M. , Muskiet Ernesto R. R. , Reyntjens Koen M. E. M. , Knotnerus Froukje H. , Oostra Martine , van Bocxlaer Jan F. P. , Struys Michel M. R. F. , Colin Pieter J.
Published: August 2019

Background

Dexmedetomidine is a sedative with modest analgesic efficacy, whereas remifentanil is an opioid analgesic with modest sedative potency. Synergy is often observed when sedative–hypnotics are combined with opioid analgesics in anesthetic practice. A three-phase crossover trial was conducted to study the pharmacodynamic interaction between remifentanil and dexmedetomidine.

Methods

After institutional review board approval, 30 age- and sex- stratified healthy volunteers were studied. The subjects received consecutive stepwise increasing target-controlled infusions of dexmedetomidine, remifentanil, and remifentanil with a fixed dexmedetomidine background concentration. Drug effects were measured using binary (yes or no) endpoints: no response to calling the subject by name, tolerance of shaking the patient while shouting the name (“shake and shout”), tolerance of deep trapezius squeeze, and tolerance of laryngoscopy. The drug effect was measured using the electroencephalogram-derived “Patient State Index.” Pharmacokinetic–pharmacodynamic modeling related the administered dexmedetomidine and remifentanil concentration to these observed effects.

Results

The binary endpoints were correlated with dexmedetomidine concentrations, with increasing concentrations required for increasing stimulus intensity. Estimated model parameters for the dexmedetomidine EC50 were 2.1 [90% CI, 1.6 to 2.8], 9.2 [6.8 to 13], 24 [16 to 35], and 35 [23 to 56] ng/ml, respectively. Age was inversely correlated with dexmedetomidine EC50 for all four stimuli. Adding remifentanil did not increase the probability of tolerance of any of the stimuli. The cerebral drug effect as measured by the Patient State Index was best described by the Hierarchical interaction model with an estimated dexmedetomidine EC50 of 0.49 [0.20 to 0.99] ng/ml and remifentanil EC50 of 1.6 [0.87 to 2.7] ng/ml.

Conclusions

Low dexmedetomidine concentrations (EC50 of 0.49 ng/ml) are required to induce sedation as measured by the Patient State Index. Sensitivity to dexmedetomidine increases with age. Despite falling asleep, the majority of subjects remained arousable by calling the subject’s name, “shake and shout,” or a trapezius squeeze, even when reaching supraclinical concentrations. Adding remifentanil does not alter the likelihood of response to graded stimuli.
Cortical Oscillations and Connectivity During Postoperative Recovery
Authors: Zierau Mackenzie , Li Duan , Lapointe Andrew P. , Ip Ka I. , McKinney Amy M. , Thompson Aleda , Puglia Michael P. , Vlisides Phillip E.
Published: August 2019

Background:

The objective of this study was to test whether postoperative electroencephalographic (EEG) biomarkers, parietal alpha power and frontal-parietal connectivity, were associated with measures of clinical recovery in adult surgical patients.

Methods:

This is a secondary analysis of a prospective cohort study that analyzed intraoperative connectivity patterns in adult surgical patients (N=53). Wireless, whole-scalp EEG data were collected in the postanesthesia care unit and assessed for relevance to clinical and neurocognitive recovery. Parietal alpha power and frontal-parietal connectivity (estimated by weighted phase lag index) were tested for associations with postanesthesia care unit discharge readiness and University of Michigan Sedation Scale scores upon postoperative admission. Bivariable correlation and regression models were constructed to test for unadjusted associations, then multivariable regression models were constructed to adjust for confounding.

Results:

Postoperative EEG patterns were characterized by a predominance of alpha parietal power and frontal-parietal connectivity. Neither relative parietal alpha power (% alpha, −0.25; 95% confidence interval [CI], −1.41 to 0.90; P=0.657) nor alpha frontal-parietal connectivity (weighted phase lag index, −82; 95% CI, −237 to 73; P=0.287) were associated with time until postanesthesia discharge criteria were met. Furthermore, neither alpha power (−0.03; 95% CI, −0.07 to 0.01; P=0.206) nor alpha frontal-parietal connectivity (−4.2; 95% CI, −11 to 2.6; P=0.226) were associated with sedation scores upon initial assessment.

Conclusions:

In a pragmatic study investigating clinically relevant endpoints of postoperative recovery, we found no correlation with surrogate measures of brain neurodynamics. These data contribute to the overall impetus of developing anesthetic-invariant and generalizable markers of brain recovery.
Calcaneal Avulsion Fractures: A Multicenter Analysis of Soft-Tissue Compromise and Early Fixation Failure
Authors: Mitchell Phillip M. , O'Neill David E. , Branch Eric , Mir Hassan R. , Sanders Roy W. , Collinge Cory A.
Published: August 2019

Objective:

To characterize the presentation and outcomes of calcaneal avulsion fractures.

Design:

Case series.

Setting:

Two ACS Level I trauma centers.

Patients/Participants:

Forty-seven calcaneal avulsion fractures isolated from a cohort of 1365 calcaneus fractures treated over a 17-year period.

Main Outcome Measurements:

We collected instances of soft-tissue compromise at presentation, evidence of implant failure or fracture displacement after fixation, and reoperation.

Results:

Forty-one patients were treated operatively, and 6 were treated without surgery. Twenty-one patients (44.7%) had either soft-tissue compromise or an open fracture necessitating urgent treatment at the time of presentation. Of those patients treated operatively with 3-month follow-up (n = 39), 28.2% of patients (11/39) had evidence of implant failure or fracture displacement. Age was the only predictor of catastrophic fixation failure (P = 0.01). The use of washer(s), suture anchor(s), or addition of soft-tissue procedures (eg, Strayer) did not have a significant effect on failure rate. Neither the number of screws used nor size of screw impacted the failure rate. Fourteen patients (35.9%) underwent a secondary operation.

Discussion:

Avulsion fractures of the calcaneus commonly present with soft-tissue compromise and have a significant rate of treatment failure and reoperation. This injury should be identified early and approached thoughtfully, acknowledging that risks are high.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Interobserver Reliability in Imaging-Based Fracture Union Assessment—Two Systematic Reviews
Authors: Ten Berg Paul W. L. , Kraan Rik B. J. , Jens Sjoerd , Maas Mario
Published: August 2019

Objectives:

(A) To investigate the specialty of observers involved in imaging-based assessment of bone fracture union in recent orthopaedic trials and (B) to provide a general overview of observer differences (in terms of interobserver reliability) in radiologic fracture union assessment that have been reported between surgeons and radiologists.

Data Sources:

Two separate systematic reviews (A, B) of English-, German-, and French-language articles in MEDLINE and Embase databases using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were done, with the following time frames: (A) January 2016–August 2017 and (B) through November 2017.

Study Selection:

(A) Clinical trials of surgical fracture treatment evaluating radiologic (non) union. (B) Interobserver studies reporting kappa-values or intraclass correlation coefficients as reliability coefficient for radiologic fracture union assessment. Inclusion criteria for both reviews were fractures of the appendicular skeleton and the use of radiographs or computed tomography.

Data Extraction:

Data were independently retrieved by 2 reviewers.

Data Synthesis:

Descriptive statistics and percentages were reported.

Results:

(A) Forty-eight trials were included, whereof 33 (68%) did not report the observer's specialty. Six trials (13%) reported surgeon observers only, and 6 (13%) reported radiologist observers only. The median number of observers is 1 (interquartile range, 1–2). (B) Thirty-one interobserver studies were included, whereof 11 (35%) included at least 1 surgeon and 1 radiologist. Interobserver reliability varied considerably across the various fracture types studied and outcome scale used and was often unsatisfactory (kappa or intraclass correlation coefficients of <0.7).

Conclusions:

In most trials providing observer's characteristics, radiologic fracture union was either rated by 1 surgeon or 1 radiologist. As interobserver reliability can be unsatisfactory, we recommend surgeons and radiologists to further intensify collaboration and trials to include at least 2 observers and associated reliability statistics.
Does Implant Choice Affect the Episode Cost of Pertrochanteric Hip Fracture for US Veterans?
Authors: Patterson Joseph T. , Takemoto Steven K. , Shearer David W. , Kuo Alfred C.
Published: August 2019

Objective:

To investigate an association between a surgeon's choice of a cephalomedullary nail (CMN) or sliding hip screw (SHS) with the cost of treating a pertrochanteric hip fracture.

Design:

Multicenter retrospective cohort study.

Setting:

US Veterans Health Administration Sierra Pacific Network.

Patients/Participants:

Two hundred ninety-four consecutive US veterans admitted for a principal diagnosis of an OTA/AO 31A-type pertrochanteric hip fracture of a native hip from 2000 to 2015.

Intervention:

Internal fixation using a CMN or an SHS.

Main Outcome Measurements:

Veterans Administration Health Economic Resource Center average national cost estimate of combined acute and postacute care episode cost, excluding implant cost, normalized to 2015 US dollars by the Consumer Price Index.

Results:

Median episode cost was $8223 lower with a CMN than an SHS (95% confidence interval, $5700–$10,746, P < 0.001) after matching on a propensity score for treatment with a CMN based on age, sex, body mass index, Charlson Comorbidity Index, fracture characteristics, study site, and admission year. A subgroup propensity-matched analysis excluding reverse obliquity pertrochanteric fractures was not sufficiently powered to detect a difference in episode cost (β = 0.76, P = 0.311).

Conclusions:

Implant choice significantly affected the episode cost of care of hip fracture at Veterans Health Administration facilities.

Level of Evidence:

Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Incidence, Predictors, and Fracture Mapping of (Occult) Posterior Malleolar Fractures Associated With Tibial Shaft Fractures
Authors: Hendrickx Laurent A.M. , Cain Megan E. , Sierevelt Inger N. , Jadav Bhavin , Kerkhoffs Gino M.M.J. , Jaarsma Ruurd L. , Doornberg Job N.
Published: August 2019

Objectives:

To (1) evaluate the incidence of posterior malleolar fractures (PMFs) in patients with tibial shaft fractures (TSFs) using advanced imaging; (2) identify predictors for patients at risk of an (occult) PMF; and (3) describe PMF characteristics to guide “malleolus-first” fixation.

Design:

Retrospective diagnostic imaging study.

Setting:

Level-I trauma center.

Patients:

One hundred sixty-four patients treated with intramedullary nailing for TSFs who underwent low-dose postoperative computed tomography (CT) scans to assess (mal)rotational alignment.

Intervention:

Analysis of advanced imaging for the presence of PMFs. Univariate and multivariate analyses to identify predictors. Qualitative analysis of PMFs by fracture mapping.

Main Outcome Measures:

(1) Incidence of PMFs in patients with TSFs as diagnosed on post-op CT scans; (2) independent predictors for the presence of PMFs; and (3) PMF patterns.

Results:

One in five patients with a TSF has an associated PMF (22%), increasing to one-in-two in patients with simple spiral fractures (56%). In 25% of patients, these fractures were occult. Univariate analysis identified simple spiral and distal third TSFs, proximal third and spiral fibula fractures, and low-energy trauma as predictors for PMFs. Multivariate analysis demonstrated that distal third and simple spiral TSFs were the only independent predictors. Haraguchi type I is the pattern specific to PMFs associated with TSF.

Conclusions:

Half of patients presenting with a simple spiral TSF have an associated PMF. In one in four patients, these are occult. Additional preoperative CT scan imaging may be considered in patients presenting with simple spiral distal third TSFs, despite negative lateral radiographs, so that PMFs can be identified and managed with “malleolus-first” fixation.

Level of Evidence:

Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Sirtuin 3, Endothelial Metabolic Reprogramming, and Heart Failure With Preserved Ejection Fraction
Authors: Zeng Heng , Chen Jian-Xiong
Published: August 2019

The incidences of heart failure with preserved ejection fraction (HFpEF) are increased in aged populations as well as diabetes and hypertension. Coronary microvascular dysfunction has contributed to the development of HFpEF. Endothelial cells (ECs) depend on glycolysis rather than oxidative phosphorylation for generating adenosine triphosphate to maintain vascular homeostasis. Glycolytic metabolism has a critical role in the process of angiogenesis, because ECs rely on the energy produced predominantly from glycolysis for migration and proliferation. Sirtuin 3 (SIRT3) is found predominantly in mitochondria and its expression declines progressively with aging, diabetes, obesity, and hypertension. Emerging evidence indicates that endothelial SIRT3 regulates a metabolic switch between glycolysis and mitochondrial respiration. SIRT3 deficiency in EC resulted in a significant decrease in glycolysis, whereas, it exhibited higher mitochondrial respiration and more prominent production of reactive oxygen species. SIRT3 deficiency also displayed striking increases in acetylation of p53, EC apoptosis, and senescence. Impairment of SIRT3-mediated EC metabolism may lead to a disruption of EC/pericyte/cardiomyocyte communications and coronary microvascular rarefaction, which promotes cardiomyocyte hypoxia, Titin-based cardiomyocyte stiffness, and myocardial fibrosis, thus leading to a diastolic dysfunction and HFpEF. This review summarizes current knowledge of SIRT3 in EC metabolic reprograming, EC/pericyte interactions, coronary microvascular dysfunction, and HFpEF.
Cardioprotective Effects of Atorvastatin Are Mediated Through PPARγ in Paraquat-Exposed Rats
Authors: Malekinejad Mojtaba , Masoumi Verki Masoumeh , Khoramjouy Mona , Alenabi Aylar , Hallaj-Salahipour Mahsa , Malekinejad Hassan
Published: August 2019

Background:

Paraquat poisoning is one of leading intoxication worldwide without an effective antidote and treatment protocol. Among the other organs, cardiotoxicity of paraquat has been frequently reported.

Aim:

The protective effects of atorvastatin (STN) on paraquat-induced cardiotoxicity and the role of peroxisome proliferator–activated receptors γ in the mediation of STN effects were investigated.

Methods:

Forty-two male Wistar rats were aliquoted into control or test groups. The animals in test groups in addition of paraquat received saline normal (PQ), pioglitazone (PGT), atorvastatin (STN), PGT + STN, PGT + GW9662, and/or STN + GW9662 for 14 days.

Results:

PGT and STN lowered lipid peroxidation rate, nitric oxide concentration, and activity of myeloperoxidase and CK/MB in the heart. PGT and STN protected from thiol molecules reduction and PQ-induced histopathological injuries. STN regulated the PQ-induced upregulation of COX-II expression in the heart. All STN-related protective effects were reversed by GW9662 as PPARγ antagonist.

Conclusions:

These data suggest a cardioprotective effect for STN against the PQ-induced inflammation and oxidative stress. The pharmacologic approach of these findings indicates that STN through PPARγ pathway lowered the PQ-induced cardiotoxicity.
Upregulating MicroRNA-203 Alleviates Myocardial Remodeling and Cell Apoptosis Through Downregulating Protein Tyrosine Phosphatase 1B in Rats With Myocardial Infarction
Authors: Zhang Jing , Pan Jianyuan , Yang Mengsi , Jin Xiaoqin , Feng Jun , Wang Ailing , Chen Zhenfei
Published: August 2019

Myocardial infarction (MI) is one of cardiovascular diseases with high incidence and mortality. MicroRNAs, as posttranscriptional regulators of genes, are involved in many diseases, including cardiovascular diseases. The aim of the present study was to determine whether miR-203 was functional in MI therapy and how it worked. Left anterior descending artery ligation and hypoxia/reoxygenation (H/R) treatment were, respectively, performed to obtain MI rats and hypoxia-injured H9c2 cells. Western blot and quantitative real-time polymerase chain reaction were used to determine protein levels and messenger RNA of relevant genes, respectively. Lentivirus-mediated overexpression of miR-203 was performed to study the miR-203 functions on left ventricular remodeling, infarct size, and cardiomyocyte apoptosis. Compared with the sham group, miR-203 levels were significantly decreased in MI and H/R groups. However, overexpressing miR-203 greatly improved the cardiac function, reduced infarct size in rats after MI and weakened infarction-induced apoptosis by increasing Bcl-2 and reducing decreasing Bax, cleaved caspase-3, and cleaved caspase-9. In addition, Protein tyrosine phosphatase 1B (PTP1B) was proved as a target of miR-203 in cardiomyocytes, and it was negatively regulated by miR-203. Further experiments indicated that PTP1B overexpression could remarkably inhibit miR-203-mediated antiapoptosis of cardiomyocytes and alleviate protective effects of miR-203 on mitochondria after H/R treatment. Altogether, miR-203 prevented infarction-induced apoptosis by regulating PTP1B, including reducing proapoptosis proteins, inactivating caspase pathway, and protecting mitochondria. In conclusion, miR-203 had abilities to alleviate MI-caused injury on myocardium tissues and reduce mitochondria-mediated apoptosis, which might be a potential target used for MI therapy.
Synthetic Cathinones and Their Potential Interactions with Prescription Drugs
Authors: Contrucci Ramon R. , Brunt Tibor M. , Inan Funda , Franssen Eric J. F. , Hondebrink Laura
Published: August 2019

Purpose:

Substance use disorder often coexists with other psychiatric disorders, resulting in the simultaneous use of recreational and prescription drugs. The authors aimed to identify potential pharmacokinetic and pharmacodynamic interactions between new psychoactive substances of the cathinone class and specific prescription drugs.

Methods:

The authors performed a systematic literature review on interactions between synthetic cathinones (mephedrone, methylone, methylenedioxypyrovalerone, and alpha-pyrrolidinopentiophenone) and antidepressants (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine), attention deficit hyperactivity disorder (ADHD) medications (atomoxetine, dexamphetamine, methylphenidate, modafinil) or HIV medications.

Results:

Although no pharmacokinetic interactions have been reported in previous literatures, such interactions are likely to occur. Metabolic pathways of cathinones, antidepressants, and ADHD medications have been shown to overlap, including metabolism via cytochrome P450 enzymes and their inhibition. Consistent with this finding, interactions of bupropion (a cathinone) with antidepressants and ADHD medications have been found to increase their serum concentrations and half-lives. Additionally, limited pharmacodynamic interactions have been reported. However, as cathinones, antidepressants, and ADHD medications have been reported to increase the extracellular monoamine concentration by affecting reuptake transporters, interactions among these compounds are likely. Presumably, even higher monoamine concentrations could be observed when cathinones are combined with prescription drugs with a similar mode of action, as has been reported in animals exposed to duloxetine and bupropion. HIV medications have a different mode of action; thus, they have been reported to be less likely to have pharmacodynamic interactions with cathinones.

Conclusions:

Clinicians should be aware of possible interactions between synthetic cathinones and prescription drugs, which may increase the risk of drug toxicity or reduce the therapeutic efficacy of the drugs. Qualitative drug screening for cathinones using mass spectrometry methods may aid the early detection of these agents.
Prednisolone Concentrations in Plasma (Total and Unbound) and Saliva of Adult Kidney Transplant Recipients
Authors: Brooks Emily , Tett Susan E. , Isbel Nicole M. , McWhinney Brett , Staatz Christine E.
Published: August 2019

Background:

Prednisolone displays significant pharmacokinetic variability and exposure–outcome relationships in renal transplant recipients, suggesting a role for drug monitoring in some scenarios. It is highly protein-bound, and the free form is pharmacologically active but cumbersome to measure. Saliva concentrations might reflect free plasma prednisolone and present an alternative measurement. The aim of this study was to examine the correlation between total and free plasma and saliva prednisolone in adult renal transplant recipients.

Methods:

Total and free plasma and saliva prednisolone concentrations were measured in 20 patients receiving oral prednisolone 1–2 months after transplant, between pre-dose and 12 hours post-dose. Prednisolone was determined using high-performance liquid chromatography mass spectrometric detection. The Pearson coefficient was used to assess the association between plasma and salivary prednisolone concentrations and area under the concentration–time curves (AUC0–12).

Results:

When considering all time points, the total and free plasma prednisolone concentrations correlated well (r2 = 0.81), but there was poor correlation between saliva and free (r2 = 0.003) and total (r2 = 0.01) plasma concentrations. When concentrations before the maximum free prednisolone plasma value were excluded, the correlation between free plasma and saliva concentrations improved (r2 = 0.57). There was a moderate correlation between free and total plasma prednisolone AUC0–12 (r2 = 0.62) using all time points, but a poor correlation between free and total plasma prednisolone AUC0–12 and saliva AUC0–12 (r2 = 0.07; r2 = 0.17).

Conclusions:

Total and free plasma prednisolone measurements correlated poorly with saliva measurements; however, correlation improved when concentrations early in the dosing interval were excluded.
Comparison of the Area Under the Curve for Vancomycin Estimated Using Compartmental and Noncompartmental Methods in Adult Patients With Normal Renal Function
Authors: Shingde Rashmi V. , Graham Garry G. , Reuter Stephanie E. , Carland Jane E. , Day Richard O. , Stocker Sophie L.
Published: August 2019

Background:

Vancomycin pharmacokinetics are best described using a 2-compartment model. However, 1-compartment population models are commonly used as the basis for dose prediction software. Therefore, the validity of using a 1-compartment model to guide vancomycin drug dosing was examined.

Methods:

Published plasma concentration–time data from adult subjects (n = 30) with stable renal function administered a single intravenous infusion of vancomycin were extracted from previous studies. The vancomycin area under the curve (AUC0–∞) was calculated for each subject using noncompartmental methods (AUCNCA) and by fitting 1- (AUC1CMT), 2- (AUC2CMT), and 3- (AUC3CMT) compartment infusion models. The optimal model fit was determined using the Akaike information criterion and visual inspection of the residual plots. The individual compartmental AUC0–∞ values from the 1- and 2-compartment models were compared with AUCNCA values using one-way repeated measures analysis of variance.

Results:

The mean (±SD) AUC estimates were similar for the different methods: AUCNCA 180 ± 86 mg·h/L, AUC1CMT 167 ± 79 mg·h/L, and AUC2CMT 183 ± 88 mg·h/L. Despite the overlapping AUC values, AUC2CMT and AUCNCA were significantly greater than AUC1CMT (P < 0.05). The 3-compartment model was excluded from the analysis because of the failure to converge in some instances.

Conclusions:

Dose prediction software using a 1-compartment model as the basis for Bayesian forecasting underestimates drug exposure (estimated as the AUC) by less than 10%. This is unlikely to be clinically significant with respect to dose adjustment. Therefore, a 1-compartment model may be sufficient to guide vancomycin dosing in adult patients with stable renal function.
Monitoring of Thyroid Malfunction and Therapies in Pregnancy and the Postpartum Period: A Systematic Updated Critical Review of the Literature
Authors: Bohnet Heinz G.
Published: August 2019

Purpose:

From the very beginning of pregnancy, the maternal thyroid has to adapt to increased thyroid hormone secretion of up to 50%. This is paralleled by changes in thyroid-stimulating hormone secretion and by the thyroid-topic action of human chorionic gonadotropin. Thus, hypothyroidism and hyperthyroidism may occur. Many women exhibit preexisting thyroid diseases. This review tries to add the most recently published approaches to diagnosing thyroid malfunction in pregnancy to existing guidelines.

Methods:

Different literature-based approaches to diagnosing thyroid malfunction during pregnancy and the postpartum period were applied. To diagnose thyroid malfunction in pregnancy, trimester-specific reference ranges for thyroid-stimulating hormone and T4 are used.

Results:

Definitions of thyroid malfunction are given. Treatment schedules for various thyroid diseases were reviewed and, on the basis of recent findings, were revised where necessary. For a daily clinical workup, this outline not only suggests diagnostic and therapeutic steps but also refers to frequent pitfalls and misinterpretations of laboratory data.

Conclusions:

Although the body of knowledge is increasing rapidly, the authors believe that this review is able to present new ideas concerning diagnostic and therapeutic tools for thyroid malfunction in pregnancy and the postpartum period. Nevertheless, there seems to remain room for individual approaches based on the personal experience of physicians who deal with these issues regularly.
Therapeutic Drug Monitoring of Olanzapine and Cytochrome P450 Genotyping in Nonsmoking Subjects
Authors: Miroshnichenko Igor I. , Pozhidaev Ivan V. , Ivanova Svetlana A. , Baymeeva Natalia V.
Published: August 2019

Background:

The relationship between a daily dose of olanzapine, its serum concentration, and the genotype of young nonsmoking men treated for schizophrenia or schizophreniform disorder was investigated in day-to-day clinical practice. Pharmacogenetics was also examined for the selected patients.

Methods:

A total of 49 participants were recruited as in-patients at the Mental Health Research Center (Moscow, Russia). Inclusion criteria were patients who had been diagnosed with schizophrenia or schizoaffective disorder (following DSM-IV guidelines) and were being treated with OLZ. A prospective, observational, open-study design was implemented. In line with the literature, patients were only included if they attained steady-state OLZ concentrations lasting for at least 8 days. A liquid chromatographic–tandem mass spectrometric method was developed for analyzing OLZ in human serum. The single cytochrome P450 polymorphisms were genotyped using an amplifier real-time polymerase chain reaction system following standard protocols.

Results:

Evidence indicating that CYP2D6 polymorphism has a significant (P = 0.046) effect on the pharmacokinetics of olanzapine was obtained, confirming the beneficial effects of therapeutic drug monitoring (TDM) for olanzapine.

Conclusions:

TDM should therefore be used as a standard care during olanzapine therapy. TDM is also useful in assessing adherence and may have a role in limiting olanzapine dosage geared at minimizing the risk of long-term toxicity.
EVALUATION OF SURGICAL FACTORS AFFECTING VITREOUS HEMORRHAGE FOLLOWING PORT DELIVERY SYSTEM WITH RANIBIZUMAB IMPLANT INSERTION IN A MINIPIG MODEL
Authors: Bantseev Vladimir , Schuetz Chris , Booler Helen S. , Horvath Joshua , Hovaten Kristof , Erickson Signe , Bentley Ellison , Nork T. Michael , Freeman William R. , Stewart Jay M. , Barteselli Giulio
Published: August 2019

Purpose:

To develop an animal model of vitreous hemorrhage (VH) to explore the impact of surgical parameters on VH associated with insertion of the Port Delivery System with ranibizumab (PDS) implant.

Methods:

Ninety eyes from 45 treatment-naive male Yucatan minipigs received PDS implant insertion or a sham procedure. The effect of prophylactic pars plana hemostasis, scleral incision length, scleral cauterization, surgical blade type/size, and viscoelastic usage on postsurgical VH was investigated.

Results:

Postsurgical VH was detected in 60.0% (54/90) of implanted eyes. A systematic effect on VH was only detected for pars plana hemostasis before the pars plana incision. The percentage of eyes with VH was 96.6% (28/29) among eyes that did not receive prophylactic pars plana hemostasis and 42.4% (24/58) among eyes that did. There was no VH in eyes that received laser ablation of the pars plana using overlapping 1,000-ms spots; pars plana cautery or diathermy was less effective. The majority of all VH cases (83.3% [45/54]) were of mild to moderate severity (involving ≤25% of the fundus).

Conclusion:

In this minipig surgical model of VH, scleral dissection followed by pars plana laser ablation before pars plana incision most effectively mitigated VH secondary to PDS implant insertion.
AN ATYPICAL CASE OF SOLAR MACULOPATHY
Authors: Bloom Steven M. , Singal Inder P.
Published: August 2019

Purpose:

To present a case of atypical solar maculopathy.

Methods:

Case report.

Results:

A 7-year-old boy who viewed an eclipse 17 months earlier had macular findings blending features of solar and laser pointer maculopathies. The right macula clinically had a central 1,000-μm, slightly irregular round area of pigmentary changes and a tiny outer macular optical coherence tomography defect. In addition, the superior fovea had a hyperreflective mound-like retinal pigment epithelial detachment extending into the outer retina. The left macula contained several, more typical solar maculopathy lesions.

Conclusion:

We describe a unique case of solar maculopathy displaying typical optical coherence tomography findings in both eyes along with a unilateral laser pointer-like hyperreflective retinal pigment epithelial detachment.
MULTIMODAL IMAGING AND TREATMENT OF SYPHILITIC CHOROIDAL NEOVASCULARIZATION
Authors: Giuffrè Chiara , Marchese Alessandro , Cicinelli Maria Vittoria , Miserocchi Elisabetta , Querques Giuseppe , Bandello Francesco , Modorati Giulio
Published: August 2019

Purpose:

To report a rare case of choroidal neovascularization (CNV) developed 2 years after successful treatment of ocular syphilis, identified by optical coherence tomography angiography.

Methods:

Case report.

Results:

A 31-year-old man with a history of syphilitic chorioretinitis developed a CNV 2 years after clinical remission of the infection. Structural optical coherence tomography (OCT) and optical coherence tomography angiography were helpful in providing detailed evidence of an extrafoveal CNV in an easy and noninvasive way. In comparison, the identification of CNV on fluorescein angiography was difficult because of the retinal blood barrier breakdown and intense choroidal background fluorescence for diffuse chorioretinal scarring of syphilitic chorioretinitis. The patient underwent 3 intravitreal injections of anti–vascular endothelial growth factor in addition to 25 mg/day of oral prednisone, with the restoration of previous visual acuity.

Conclusion:

Choroidal neovascularization is a rare, but sight-threatening complication of syphilitic chorioretinitis. The combination of different imaging modalities, and in particular optical coherence tomography angiography, allowed reaching a definite diagnosis of CNV. Combined treatment of systemic steroid and intravitreal anti–vascular endothelial growth factor was effective in controlling the CNV and improving the visual outcome.
XEN Gel Stent to Treat ICE Syndrome: 4 Cases
Authors: Lin Michael M. , Morgan William H. , Kolomeyer Natasha N. , Moster Stephen J. , Zheng Cindy X. , Giubilato Antonio , Moster Marlene R.
Published: August 2019

Précis:

This case series reports safe, effective implantation of XEN gel stents to treat iridocorneal endothelial (ICE) syndrome. The stents continue to function well and have not been occluded by membranes or peripheral anterior synechiae, but continued follow-up is necessary.

Purpose:

ICE syndrome-related glaucoma is often refractory to medical treatment, and traditional surgical treatment has lower success rates than typical for other types of glaucoma. We present a series of patients who were treated with XEN gel stent implantation.

Patients and Methods:

Retrospective case series of 4 patients with ICE syndrome who underwent XEN with subconjunctival mitomycin C injection.

Results:

Average preoperative intraocular pressure was 28.5 mm Hg on 3.8 glaucoma medications, and average postoperative intraocular pressure was 10.5 mm Hg on 1.0 medication. No patients required return to the operating room for additional procedures over an average of 6.9 months of follow-up. One patient had shallow anterior chamber that resolved with conservative management. Another had shallow anterior chamber that resolved with anterior chamber reformation with viscoelastic and developed nonappositional choroidal effusions that had resolved at most recent follow-up of 7 months after surgery. No XEN implants have been occluded by membrane formation or peripheral anterior synechiae.

Conclusions:

XEN is a safe and effective option for surgical management of ICE syndrome-related glaucoma. Further follow-up surveillance is necessary.
Cell type–specific super-resolution imaging reveals an increase in calcium-permeable AMPA receptors at spinal peptidergic terminals as an anatomical correlate of inflammatory pain
Authors: Woodhams Stephen G. , Markus Robert , Gowler Peter R.W. , Self Timothy J. , Chapman Victoria
Published: August 2019

Spinal hyperexcitability is a key event in the development of persistent pain, and arises partly from alterations in the number and localization of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate receptors. However, determining precisely where these changes occur is challenging due to the requirement for multiplex labelling and nanoscale resolution. The recent development of super-resolution light microscopy provides new tools to address these challenges. Here, we apply combined confocal/direct STochastic Optical Reconstruction Microscopy (dSTORM) to reveal changes in calcium-permeable subunits of AMPA-type glutamate receptors (GluA1) at identified spinal cord dorsal horn (SCDH) peptidergic axon terminals in a model of inflammatory pain. L4/5 lumbar spinal cord was collected from adult male C57BL/6J mice 24 hours after unilateral hind paw injection of saline or 1% carrageenan (n = 6/group). Tissue was immunolabelled for markers of peptidergic axon terminals (substance P; SP), presynaptic active zones (Bassoon), and GluA1. Direct stochastic optical reconstruction microscopy revealed a 59% increase in total GluA1 immunolabelling in the SCDH in the carrageenan group, which was not detected by confocal microscopy. Cell type–specific analyses identified a 10-fold increase in GluA1 localized to SP+ structures, and identified GluA1 nanodomains that scaled with behavioural hypersensitivity, and were associated with synaptic release sites. These findings demonstrate that dSTORM has the sensitivity and power to detect nanoscale anatomical changes in the SCDH, and provides new evidence for synaptic insertion of GluA1+-AMPA-Rs at spinal peptidergic nociceptive terminals in a model of inflammatory pain.
Single nucleotide polymorphism rs11191454 in arsenite methyltransferase is associated with flow in Chinese students: a genetic study on flow experience
Authors: Chen Zhixuan , Liu Chuanxin , An Lin , Zhang Naixin , Ren Decheng , Yuan Fan , Yuan Ruixue , Bi Yan , Sun Qianqian , Ji Lei , Guo Zhenming , Ma Gaini , Xu Fei , Shi Lei , Yang Fengping , Du Li , Zhu Liping , Xu Yifeng , He Lin , Bai Bo , Yu Tao , Li Xingwang , He Guang
Published: August 2019

Flow has been widely studied in the field of positive psychology. However, little is known regarding its biological mechanism. This study aimed to ascertain flow-related gene loci. We investigated the association between flow and five single nucleotide polymorphisms associated with common mental disorders among a sample of 870 healthy 1
st
year students of Jining Medical University, Shandong Province, China. This study was approved by the Ethics Committee of Jining Medical University (approval number: JNMC-2016-KY-001) on June 1, 2016. rs11191454 demonstrated significant statistical association with flow after adjusting for age and gender (
P
= 0.004). The allele carriers achieved higher scores in all 4 dimensions of flow: merging of action and awareness, challenge-skill balance, sense of control, and clear goals. This biological research article indicates that rs11191454 in the arsenite methyltransferase (
AS3MT
) gene might be associated with flow in a Chinese Han population, and that might result from altered arsenic metabolism.
Where are we now? Practice-level utilization of nurse practitioners in comparison with state-level regulations
Authors: Zwilling Jana G. , Fiandt Kathryn
Published: August 2019

Background and purpose:

Full practice authority for nurse practitioners (NPs) is optimal for high-quality, cost-effective health care. However, a complete picture of utilization after states have adopted full practice authority needs to be determined. The purpose of this examination was to review the evidence regarding practice-level utilization (PLU) of NP PLU in comparison to state-level regulations (SLRs).

Methods:

Studies published in English and based on US populations were identified through PubMed, CINAHL, and Scopus (January 1, 1989–December 31, 2018), and bibliographies of retrieved articles. Of the 419 articles identified with these limits, 19 (5%) met all inclusion and exclusion criteria.

Conclusions:

Four categories of PLU were identified: billing practices, level of supervision, privileges, and prescriptive authority. Significant differences were seen between urban versus rural NPs and primary care versus specialty NPs. Thirteen of the 19 studies did not specifically address the SLR of the included sample.

Implications for practice:

No studies described the type of NP certification, practice specialty, and utilization, and compared all to the SLR. There is a need for more evidence concerning PLU of NPs across the tiers of SLR. Only then can health care organizations, political leaders, and other stakeholders have the information needed to proceed with beneficial practice-model changes.
Occipital and Cerebellar Theta Burst Stimulation for Mal De Debarquement Syndrome
Authors: Cha Yoon-Hee , Gleghorn Diamond , Doudican Benjamin
Published: August 2019

Background:

Individuals with Mal de Debarquement syndrome (MdDS) experience persistent oscillating vertigo lasting for months or years. Transcranial magnetic stimulation (TMS) can modulate the motion perception of MdDS.

Materials and Methods:

Twenty-six TMS naive individuals received single administrations of continuous theta burst stimulation (cTBS) over the occipital cortex, cerebellar vermis, and lateral cerebellar hemisphere, in randomized order. A 0–100 point Visual Analogue Scale was used to assess acute changes in oscillating vertigo severity after each session. Repeated treatments were given over the target that led to the most acute reduction in symptoms. All treatments were performed with neuronavigation using the participant's own brain MRI. The Dizziness Handicap Inventory (DHI), MdDS Balance Rating Scale (MBRS), and Hospital Anxiety and Depression Scale (HADS) were assessed weekly at four pretreatment and six posttreatment time points.

Results:

Twenty participants chose either the occipital cortex (11) or cerebellar vermis (9) targets as most effective in reducing the oscillating vertigo; one chose lateral cerebellar hemisphere; five chose none. After 10 to 12 sessions of 1,200 pulses over the target of choice, 19 of 25 treatment completers noted ≥ 25% reduction, 12 of 25 ≥50% reduction, and 8 of 25 ≥75% reduction in oscillating vertigo intensity. A one-way repeated measures ANOVA of DHI, MBRS, and HADS scores before and after treatment showed significant reductions in DHI, MBRS, and the HADS Anxiety subscore immediately after treatment with most improvement lasting through posttreatment week 6. There were no significant Depression subscore changes. Participants who had chosen vermis stimulation had comparatively worse balance at baseline than those who had chosen occipital cortex stimulation.

Conclusion:

cTBS over either the occipital cortex or cerebellar vermis is effective in reducing the oscillating vertigo of MdDS acutely and may confer long-term benefits. Sustained improvement requires more frequent treatments.
Sedation Practices of Neonates Receiving Extracorporeal Membrane Oxygenation
Authors: Franciscovich Christine D. , Monk Heather M. , Brodecki Darcy , Rogers Rachel , Rintoul Natalie E. , Hedrick Holly L. , Ely Elizabeth
Published: August 2019

Neonatal sedation practices during extracorporeal membrane oxygenation (ECMO) are not well described and no universal guidelines exist. Current literature describes types of medications used in adult and pediatric ECMO patients, but to our knowledge no data is published on neonatal specific median daily dose requirements or descriptions of sedation practices. The objective of this study is to examine the types and median doses of sedation utilized and to describe sedation practices for neonatal patients requiring ECMO support. This study was a descriptive, retrospective analysis of sedation practices in a single center newborn/infant intensive care unit (N/IICU) from 2012 to 2016. Subjects included all neonates who required ECMO support in the N/IICU for >24 hours. Data were collected from 87 patients and showed the median daily dose of opioids converted to intravenous morphine equivalents was 1.2, 2.0, and 3.4 mg/kg on ECMO days 1, 7, and 14, respectively. The most commonly used continuous medication infusions included morphine, midazolam, and hydromorphone. Dexmedetomidine was used in eight patients and ketamine in two patients. Doses of opioids and sedatives typically escalated over time. Pain scores did not correlate with sedation or analgesic administrations.
Early Decompressive Laparotomy for Intra-Abdominal Hypertension Following Initiation of Venovenous Extracorporeal Membrane Oxygenation
Authors: Boulos Francesca M. , Pasrija Chetan , DiChiacchio Laura , Rouse Michael , Raithel Maxwell , Mackowick Kristen , Rector Raymond , Mazzeffi Michael A. , Griffith Bartley P. , Diaz Jose J. , Kon Zachary N. , Deatrick Kristopher B.
Published: August 2019

Patients supported with venovenous extracorporeal membrane oxygenation are at risk for intra-abdominal hypertension and abdominal compartment syndrome. Flow through the return cannula may be compromised in these patients, resulting in inadequate support and end-organ malperfusion. Early decompressive laparotomy can mitigate these complications and potentially improve outcomes. Here we review a series of nine patients undergoing early decompressive laparotomy for abdominal compartment syndrome at a single institution and propose an algorithmic approach to the management of these patients.
Nitric Oxide Attenuates the Inflammatory Effects of Air During Extracorporeal Circulation
Authors: Toomasian John M. , Jeakle Mark M.P. , Langley Mark W. , Poling Clinton J. , Lautner Gergely , Lautner-Csorba Orsolya , Meyerhoff Mark M. , Carr Ben jamin D. , Rojas-Pena Alvaro , Haft Jonathan W. , Bartlett Robert H.
Published: August 2019

Cardiopulmonary bypass causes a systemic inflammatory response reaction that may contribute to postoperative complications. One cause relates to the air/blood interface from the extracorporeal circuit. The modulatory effects of blending nitric oxide (NO) gas into the ventilation/sweep gas of the membrane lung was studied in a porcine model of air-induced inflammation in which NO gas was added and compared with controls with or without an air/blood interface. Healthy swine were supported on partial bypass under four different test conditions. Group 1: no air exposure, group 2: air alone, group 3: air plus 50 ppm NO, and group 4: air plus 500 ppm NO. The NO gas was blended into the ventilation/sweep site of the membrane lung. The platelets and leucocytes were activated by air alone. Addition of NO to the sweep gas attenuated the inflammatory response created by the air/blood interface in this model.