bluuebunny/crossref_metadata_2025 huggingface dataset:
A Nonparametric Pharmacokinetic Approach to Determine the Optimal Dosing Regimen for 30-Minute and 3-Hour Meropenem Infusions in Critically Ill Patients
Authors: Mathew Sumith K. , Mathew Binu S. , Neely Michael N. , Naik Girish S. , Prabha Ratna , Jacob Gijoe G. , K Subramani , Fleming Denise H.
Published: July 2016

Background:

Pharmacokinetics of meropenem differ widely in the critically ill population. It is imperative to maintain meropenem concentrations above the inhibitory concentrations for most of the interdose interval. A population pharmacokinetic/pharmacodynamic model was developed to determine the probability of target attainment for 3-hour and 30-minute infusion regimens in this population.

Methods:

This study was performed in an intensive care setting among adult patients who were initiated on meropenem at a dose of 1000 mg. Multiple blood specimens were collected at predetermined time points during the interdose period, and meropenem concentrations were measured using high performance liquid chromatography. Using Pmetrics, a pharmacokinetic/pharmacodynamic model was developed and validated. Monte Carlo simulation was performed, and probability of target attainment (100% T > minimum inhibitory concentration (MIC), with a probability >0.9) for doubling MICs was determined for different regimens of meropenem.

Results:

A 2-compartment multiplicative gamma error model best described the population parameters from 34 patients. The pharmacokinetic parameters used in the final model were Ke (elimination rate constant from the central compartment), Vc (volume of distribution of central compartment), KCP and KPC (intercompartmental rate constants), and IC2 (the fitted amount of meropenem in the peripheral compartment). Inclusion of creatinine clearance (CLcreat) and body weight as covariates improved the model prediction (Ke = Ke0 ×

JOURNAL/thdm/04.03/00007691-201610000-00006/inline-formula1/v/2023-08-14T200353Z/r/image-tiff

, Vc = Vc0 × Weight0.5). The Ke and Vc [geometric mean (range)] of the individuals were 0.54 (0.01–2.61)/h and 9.36 (4.35–21.62) L, respectively. The probability of attaining the target, T > MIC of 100%, was higher for 3-hour infusion regimens compared with 30-minute infusion regimens for all ranges of CLcreat.

Conclusions:

This study emphasizes that extended regimens of meropenem are preferable for treating infections caused by bacteria with higher MICs. The nonparametric analysis using body weight and CLcreat as covariate adequately predicted the pharmacokinetics of meropenem in critically ill patients with a wide range of renal function.
Mucormycosis of the Forehead and Sinuses in a Trauma Patient
Authors: Kumbla Pallavi A. , Lee Nathan , Kimbrough Mary K.
Published: July 2016

Mucormycosis is a rare fungal infection in immunocompetent patients. It is not commonly seen in trauma patients who sustain multisystem injuries and are often exposed to numerous infectious sources. A multidisciplinary approach between medical and surgical specialties is crucial to ensuring timely diagnosis and treatment as morbidity and mortality can be high once acquired. In addition to antifungal therapy, radical debridement and reconstruction by plastic surgery is often necessary. Review of the literature shows that there is no definitive reconstructive technique for mucormycosis of the forehead and sinuses because the amount of tissue destruction may be varied in location and depth, therefore requiring varying extents of debridement. However, other reconstructive techniques commonly used for oncologic and trauma reconstructions can be used to achieve functionality and a satisfactory cosmetic result. Few facial reconstructions after infection with mucormycosis have been documented in the literature.
Initial Experience Using Closed Incision Negative Pressure Therapy after Immediate Postmastectomy Breast Reconstruction
Authors: Gabriel Allen , Sigalove Steven R. , Maxwell G. Patrick
Published: July 2016

Although immediate postmastectomy breast reconstruction is favored over delayed reconstruction, it remains associated with high complication rates. Potential complications include seroma formation, dehiscence, infection, and tissue necrosis along incision edges. Closed incision negative pressure therapy (ciNPT; Prevena Incision Management System, KCI, an Acelity company, San Antonio, Tex.) has been reported to help hold incision edges together, protect incisions from external contamination, and remove fluid and infectious material. We investigated outcomes of applying ciNPT with a customizable dressing over closed incisions in 13 patients (25 breasts) who received immediate postmastectomy reconstruction as part of 2-stage expander/implant breast reconstruction. Nipple-sparing mastectomy was performed on 14 breasts, reduction-pattern mastectomy on 6 breasts, and skin-sparing mastectomy on 5 breasts. All breasts had ciNPT with a customizable dressing applied over the entire clean closed incision immediately after surgery at −125 mmHg for an average of 4.3 days. At 3-month follow-up, 24 of the 25 (96%) breasts had achieved healing. Delayed hematoma occurred on postoperative day 13 in 1 breast in the nipple-sparing mastectomy group and resolved. In the reduction-pattern mastectomy group, superficial dehiscence occurred on 3 breasts and resolved with local wound care. One breast in that group developed flap necrosis requiring surgical revision. Less drainage was observed in attached closed-suction drains, so time to drain removal was reduced from an estimated average of 12–14 days to 8.2 days. Based on the initial experience in this study, larger studies are warranted to evaluate the use of ciNPT with customizable or peel-and-place dressings after immediate postmastectomy breast reconstruction.
Meal frequency and timing: impact on metabolic disease risk
Authors: Varady Krista A.
Published: July 2016

Purpose of review

The purpose of this article is to provide an overview of the most recent human intervention trials that have examined the impact of meal frequency or meal timing on metabolic disease risk factors.

Recent findings

Findings from intervention studies published over the past 12 months indicate that weight loss may be more pronounced with decreased meal frequency (two meals per day) versus increased meal frequency (six meals per day) under hypocaloric conditions. However, under isocaloric conditions, no effect on body weight was noted. Plasma lipid concentrations and glucoregulatory factors (fasting glucose, insulin, and insulin sensitivity) were not affected by alterations in meal frequency. As for meal timing, delaying the lunchtime meal by 3.5 h (from 1.30 p.m. to 4.30 p.m.) has no impact on body weight, but may impair glucose tolerance in young healthy adults.

In sum, altering meal frequency has little impact on body weight, plasma lipids, or glucoregulatory factors, whereas eating the majority of calories later in the day may be detrimental for glycemic control. These preliminary findings, however, still require confirmation by longer term, larger scale controlled trials.
Comparison of patency and cost-effectiveness of self-expandable metal and plastic stents used for malignant biliary strictures: a Polish single-center study
Authors: Budzyńska Agnieszka , Nowakowska-Duława Ewa , Marek Tomasz , Hartleb Marek
Published: July 2016

Introduction

Most patients with malignant biliary obstruction are suited only for palliation by endoscopic drainage with plastic stents (PS) or self-expandable metal stents (SEMS).

Objective

To compare the clinical outcome and costs of biliary stenting with SEMS and PS in patients with malignant biliary strictures.

Patients and methods

A total of 114 patients with malignant jaundice who underwent 376 endoscopic retrograde biliary drainage (ERBD) were studied.

Results

ERBD with the placement of PS was performed in 80 patients, with one-step SEMS in 20 patients and two-step SEMS in 14 patients. Significantly fewer ERBD interventions were performed in patients with one-step SEMS than PS or the two-step SEMS technique (2.0±1.12 vs. 3.1±1.7 or 5.7±2.1, respectively, P<0.0001). The median hospitalization duration per procedure was similar for the three groups of patients. The patients’ survival time was the longest in the two-step SEMS group in comparison with the one-step SEMS and PS groups (596±270 vs. 276±141 or 208±219 days, P<0.001). Overall median time to recurrent biliary obstruction was 89.3±159 days for PS and 120.6±101 days for SEMS (P=0.01). The total cost of hospitalization with ERBD was higher for two-step SEMS than for one-step SEMS or PS (1448±312, 1152±135 and 977±156€, P<0.0001). However, the estimated annual cost of medical care for one-step SEMS was higher than that for the two-step SEMS or PS groups (4618, 4079, and 3995€, respectively).

Conclusion

Biliary decompression by SEMS is associated with longer patency and reduced number of auxiliary procedures; however, repeated PS insertions still remain the most cost-effective strategy.
No difference in mortality between terlipressin and somatostatin treatments in cirrhotic patients with esophageal variceal bleeding and renal functional impairment
Authors: Hung Tsung-Hsing , Tsai Chen-Chi , Tseng Chih-Wei , Tseng Kuo-Chih , Hsieh Yu-Hsi , Tsai Chih-Chun
Published: July 2016

Objective

To study the differences in mortality between terlipressin and somatostatin treatments in cirrhotic patients with esophageal variceal bleeding (EVB) and renal functional impairment (RFI).

Methods

The National Health Insurance Database, part of the Taiwan National Health Insurance Program, was used to enroll cirrhotic patients who had received endoscopic variceal ligation plus somatostatin or terlipressin for EVB and who were hospitalized between 1 January 2007 and 31 December 2010. The differences in mortality between the two vasoactive agents were compared and the risk factors for 30-day mortality because of EVB were identified.

Results

A total of 2324 cirrhotic patients with EVB were enrolled. The 30-day mortality data showed no significant differences between the somatostatin and the terlipressin groups (P=0.232). The risk of 30-day mortality was significantly higher in male patients [hazard ratio (HR): 1.50, P=0.002] and patients with hepatic encephalopathy (HR: 1.82, P<0.001), ascites (HR: 1.32, P=0.008), bacterial infections (HR: 2.10, P<0.001), hepatocellular carcinoma (HR: 2.09, P<0.001), and RFI (HR: 3.89, P<0.001). A subgroup analysis of cirrhotic patients with RFI was carried out. The overall 30-day mortality was higher in patients treated with somatostatin than in those treated with terlipressin (52.6 vs. 42.3%), but the difference failed to reach significance (adjust HR: 1.49, 95% confidence interval: 0.94–2.37, P=0.091).

Conclusion

RFI was the most important risk factor for 30-day mortality in EVB patients. Terlipressin and somatostatin had similar effects on 30-day mortality in cirrhotic patients with EVB and RFI.
The 4-hour standard is a meaningful quality indicator: correlation of performance with emergency department crowding
Authors: Higginson Ian , Kehoe Anthony , Whyatt Justin , Smith Jason E.
Published: July 2016

Background

The 4-h standard performance is a controversial quality indicator. Crowding in emergency departments (EDs) causes increased patient morbidity and mortality. The aim of this study was to investigate the relationship between 4-h standard performance and ED crowding as measured by occupancy.

Methods

A retrospective observational study was carried out using the computerized Emergency Department Information System. Daily occupancy was considered in three ways: as minutes per day spent at occupancy thresholds of 70, 80, 90 and 100%; as the peak occupancy of resuscitation and majors beds at any point in the day; and as a percentage of the total potential ED bed minutes used during the day.

Results

An inverse relationship was observed between occupancy and 4-h standard performance using each method. Performance could be sustained at 70% occupancy, but deteriorated in a linear manner at a progressively increasing rate at 80, 90 and 100% occupancy (all P<0.01). A stepwise decrease in the mean performance was observed with increasing peak occupancy (P<0.001). A similar decrease in performance was observed with increasing 24-h overall occupancy (P<0.001).

Conclusion

This study has identified a clear and consistent correlation between ED crowding and performance against the 4-h standard. Because crowding is associated with harm, the 4-h standard is a meaningful quality metric for UK hospitals. Systematic measurement of ED crowding using occupancy may play a role in improving the quality of care delivered within the urgent care system.
Red blood cell alloimmunization: new findings at the bench and new recommendations for the bedside
Authors: Hendrickson Jeanne E. , Eisenbarth Stephanie C. , Tormey Christopher A.
Published: July 2016

Purpose of review

To summarize recent discoveries from clinical studies and animal models that contribute to understanding the alloimmune response to non-ABO blood group antigens.

Recent findings

Several studies have confirmed high rates of alloimmunization among patients requiring chronic red blood cell (RBC) transfusion. Moreover, ‘triggers’ for alloantibody development in the transfusion setting have been identified, with a number of investigations linking recipient inflammation to a higher likelihood of alloimmunization. Additional associations between human leukocyte antigen expression and CD4+ T-cell markers in ‘responder’ or ‘nonresponder’ humans have been revealed. Recent animal studies have described novel mechanistic properties by which the alloimmune response is governed, including the critical role played by dendritic cells in transfusion-associated alloimmunization. New light has also been shed on the properties of alloantibodies developed as a result of pregnancy, as well as mechanisms through which such alloimmunization may be prevented.

Many of the clinical/biological factors that contribute to the RBC alloimmune response have been further elucidated. This knowledge will be applied to identify individuals most likely to mount an immune response to RBC antigens, such that appropriate resources and strategies for preventing alloimmunization (or mitigating its harmful effects) can be implemented.
Minimizing free flap donor-site morbidity
Authors: Harris Brianna N. , Bewley Arnaud F.
Published: July 2016

Purpose of review

Fasciocutaneous and osteocutaneous free flap reconstruction has significantly changed the way surgeons reconstruct defects following ablation of head and neck tumors. Over time, success rates of free flaps have approached 98%, allowing surgeons to shift their focus to minimizing morbidities associated with the donor sites. The radial forearm, anterolateral thigh, and fibula free flaps are the three most commonly used flaps in head and neck reconstruction, and therefore each of their advantages and associated morbidities are of particular interest. The present article aims to review the morbidities associated with each of the commonly used head and neck free flaps and techniques to minimize them that are described in the most recent literature.

Recent findings

New techniques such as negative-pressure wound therapy, full thickness grafts, and rotational flaps have been developed recently that minimize these morbidities.

The techniques described in the current review may improve long-term patient outcomes both esthetically and functionally.
What Do Ovarian Cancer Patients Expect From Treatment?
Authors: Simacek Kristina , Raja Priya , Chiauzzi Emil , Eek Daniel , Halling Katarina
Published: July 2016

Background:

Advances in ovarian cancer treatment have improved outcomes. However, the gap between patients’ hopes and expectations and their actual outcomes remains an understudied aspect of treatment decision making. This gap has been noted to be a predictor of poorer health-related quality of life. Incorporating patient hopes and expectations for treatment into clinical care may improve patient experiences.

Objectives:

The aim of this study is to describe the hopes and expectations of ovarian cancer patients at diagnosis and throughout treatment transitions.

Methods:

This study sampled from an online community of patients with ovarian cancer. Thirty members completed an online qualitative survey about their diagnostic and treatment journey, including hopes and expectations around treatment.

Results:

Initially, ovarian cancer patients hoped for a complete cure or removal of cancer. As they progressed through treatment, hopes and expectations centered on issues related to living with ovarian cancer. A subset of patients emphasized a lack of information about treatment side effects.

Conclusions:

The shift in expectations from survival to living with ovarian cancer may demonstrate an enhanced understanding of ovarian cancer prognosis as patients learn more about their condition. Patients underscored that a more involved discussion of side effect profiles with clinicians would enhance their treatment decision making and expectation setting process.

Implications for Practice:

Expectation setting may be improved by contextualizing treatment in terms of the transitions ovarian cancer patients experience. Providing relevant information that aligns with patient needs, desires, and concerns at critical transitions may improve clinical care and decision making.
Examining the Relationship Between Clinical Judgment and Nursing Actions in Prelicensure Students
Authors: Stuedemann Fedko Andrea , Thomas Dreifuerst Kristina
Published: July 2016

Faculty frequently use the Lasater Clinical Judgment Rubric (LCJR) to identify students’ clinical judgment; however, it is unclear whether LCJR scores relate to appropriate nursing action. In a pilot study consisting of senior-level nursing students (N = 22), participants were scored on the LCJR and anticipated nursing actions, and results were analyzed using simple linear regression. There was a statistically significant correlation (r = 0.364) between clinical judgment and nursing action. Results suggest that total LCJR scores may be an indicator of the completion of indicated nursing action.
Appreciative Advising in Nursing Education
Authors: Read Aggie , Hicks Jennifer , Christenbery Tom
Published: July 2016

The 6-phase Appreciative Advising framework for academic advising has been incorporated into a nursing program in the southeast United States, with promising initial results. Historical perspectives of academic advising, an overview of Appreciative Advising, and implementation of the framework are presented.
Predictors of Outcome in the Phenotypic Spectrum of Polymorphous Low-grade Adenocarcinoma (PLGA) and Cribriform Adenocarcinoma of Salivary Gland (CASG)
Authors: Xu Bin , Aneja Amandeep , Ghossein Ronald , Katabi Nora
Published: July 2016

Polymorphous low-grade adenocarcinoma (PLGA) shows histologic diversity with fascicular and targetoid features while cribriform adenocarcinoma of salivary gland (CASG) demonstrates predominant cribriform and solid patterns with glomeruloid appearance and optical clear nuclei. The current study is designed to identify pathologic features that may predict clinical outcome in 69 PLGA/CASG. Seven patients had recurrences or distant metastasis, including 3 local recurrences, 2 nodal metastases, and 2 distant metastases. The following histologic factors predicted disease-free survival on univariate analysis: tumor size, bone invasion, lymphovascular invasion, tumor necrosis, ≥10% papillary pattern, and ≥30% cribriform pattern. On multivariate analysis, 10% of papillary pattern and 30% cribriform pattern were independent prognostic factors of disease-free survival. Histologic classification of the 69 tumors (based on the prior reported definition of CASG) showed 21 CASGs (30%), 23 PLGAs (33%), and 22 (32%) with indeterminate features of PLGA and CASG. In addition, 3 (4%) tumors demonstrated a predominant papillary pattern (≥50%). Interestingly, not all CASGs were located in the minor salivary gland and 2 tumors were identified in the parotid. One patient died from her disease and she harbored a CASG with >30% cribriform pattern. In conclusion, tumor size, bone invasion, and lymphovascular invasion are significant parameters that can predict adverse clinical behaviors in PLGA/CASG on univariate analysis. Using the prior reported definition, an overlapping histology between PLGA and CASG was noted in over a third of the cases. Regardless of tumor subclassification, the percentage of cribriform and papillary patterns seems to be prognostically relevant and should be documented.
OsmoPrep-associated Gastritis
Authors: Matsukuma Karen , Gui Dorina , Olson Kristin A. , Tejaswi Sooraj , Clayton Erica F. , Thai Anne
Published: July 2016

We have identified 8 cases of gastritis characterized by the presence of purple to black granular deposits in the superficial mucosa associated with marked reactive epithelial changes. In each case, the patient had taken OsmoPrep, a tablet form of sodium phosphate used for bowel preparation just before upper endoscopy and had undergone concurrent colonoscopy. Endoscopic findings ranged from normal gastric mucosa to severe inflammation, congestion, and friability. No other gastrointestinal sites were noted to contain the deposits or show similar mucosal injury. On initial histologic review, the deposits raised the differential diagnosis of elemental iron and mucosal calcinosis. However, none of the patients was noted to be taking iron supplements, and none had a history of renal disease or other cause of calcium dysmetabolism. Histochemical stains revealed the deposits were negative on Perls’ iron stain (8/8 cases), positive on von Kossa stain (7/8 cases), and negative on Alizarin Red stain (8/8 cases)—a histochemical profile compatible with sodium phosphate but inconsistent with mucosal calcium. A crushed OsmoPrep tablet was subjected to processing and demonstrated similar histologic features and histochemical profile. In addition, biopsies of 20 consecutive patients who did not take OsmoPrep and who underwent concurrent endoscopy and colonoscopy were reviewed, and no deposits with similar histochemical profile were identified. In summary, we have characterized a unique form of gastritis associated with OsmoPrep use. Attention to clinical history and use of a select panel of histochemical stains allow for accurate diagnosis.
Ciliated Muconodular Papillary Tumors of the Lung Can Occur in Western Patients and Show Mutations in BRAF and AKT1
Authors: Liu Liping , Aesif Scott W. , Kipp Benjamin R. , Voss Jesse S. , Daniel Silver , Aubry Marie Christine , Boland Jennifer M.
Published: July 2016

Ciliated muconodular papillary tumors (CMPTs) are rare peripheral lung lesions, characterized by papillary architecture and ciliated columnar cells admixed with mucinous cells and basal cells. They often have prominent surrounding intra-alveolar mucin, which can lead to diagnostic confusion with mucinous adenocarcinoma. Recognition of the ciliated component is the key to diagnosis of CMPT. The literature contains few reported cases to date, all occurring in East-Asian patients. Although follow-up data are limited, CMPT seems to be an indolent tumor with very good prognosis, leading some to question whether it is a reactive or hamartomatous lesion. However, a very recent molecular study has identified BRAF (40%) and EGFR (30%) alterations in CMPT, supporting a truly neoplastic process. Here for the first time, we report 4 cases of morphologically typical CMPT in western patients, occurring in 1 man (60 y) and 3 women (71 to 83 y). Interestingly, 1 case occurred in background of pronounced small airway disease with necrotizing bronchiolitis and multiple carcinoid tumorlets. We further analyzed 1 tumor using a 50 gene next-generation sequencing oncology panel that identified 2 pathogenic mutations (BRAF V600E and AKT1 E17K). Our study is the first to describe that CMPT can occur in western (non-Asian) patients. Our data confirm BRAF V600E mutation as a probable driver in a subset of these tumors, along with AKT1 mutation, which further supports that CMPT are indolent pulmonary neoplasms.
Solitary Pulmonary Capillary Hemangioma of Adult Cases
Authors: Hashimoto Hirotsugu , Kurata Atsushi , Fujiwara Masachika , Hara Kei , Matsumoto Jun , Kusakabe Masashi , Tachibana Keisei , Nashiro Tamaki , Terado Yuichi , Akahane Masaaki , Usui Kazuhiro , Suzuki Yoshio , Kondo Haruhiko , Kamma Hiroshi , Kuroda Masahiko , Horiuchi Hajime
Published: July 2016

Solitary pulmonary capillary hemangioma (SPCH) is a rare disease, first described about autopsy cases in 2000 and about surgically resected cases in 2006. To date, only 9 surgically resected cases have been published in English. Here, we report 7 original cases with surgery (median age, 54 y; 4 females, 2 never-smokers). All patients were asymptomatic, and all nodules were detected by computed tomography (CT). The median (range) size of nodule was 11 (8 to 16) mm. Six of 7 cases showed the part-solid nodule appearance and 1 showed pure ground-glass nodule appearance in CT findings. The growth speed was very slow. No abnormal uptake of fluorine-18 fluorodeoxyglucose was observed in systemic positron-emission CT in all 3 cases we examined. No patients died from SPCH. Histologically, SPCH manifested as a solitary lesion composed of densely proliferating and dilated capillaries without cytologic atypia within the alveolar septa. In addition, capillaries of SPCH spread into the vascular lumen and involved the walls of bronchioles with protrusion into the lumen. Immunohistochemically, capillaries of SPCH uniformly expressed endothelial markers, such as CD31, CD34, and Factor VIII; and α-smooth muscle actin positive cells were also observed. To be accurately diagnosed, especially in intraoperative frozen sections, SPCH should be conceived as an entity that presents as a solitary nodule in CT. We propose that SPCH is an unrecognized benign capillary proliferative disease.
Protocolized Treatment Is Associated With Decreased Organ Dysfunction in Pediatric Severe Sepsis*
Authors: Balamuth Fran , Weiss Scott L. , Fitzgerald Julie C. , Hayes Katie , Centkowski Sierra , Chilutti Marianne , Grundmeier Robert W. , Lavelle Jane , Alpern Elizabeth R.
Published: July 2016

Objectives:

To determine whether treatment with a protocolized sepsis guideline in the emergency department was associated with a lower burden of organ dysfunction by hospital day 2 compared to nonprotocolized usual care in pediatric patients with severe sepsis.

Design:

Retrospective cohort study.

Setting:

Tertiary care children’s hospital from January 1, 2012, to March 31, 2014.

Subjects:

Patients older than 56 days old and younger than 18 years old with international consensus defined severe sepsis and who required PICU admission within 24 hours of emergency department arrival were included.

Measurements and Main Results:

The exposure was the use of a protocolized emergency department sepsis guideline. The primary outcome was complete resolution of organ dysfunction by hospital day 2. One hundred eighty nine subjects were identified during the study period. Of these, 121 (64%) were treated with the protocolized emergency department guideline and 68 were not. There were no significant differences between the groups in age, sex, race, number of comorbid conditions, emergency department triage level, or organ dysfunction on arrival to the emergency department. Patients treated with protocolized emergency department care were more likely to be free of organ dysfunction on hospital day 2 after controlling for sex, comorbid condition, indwelling central venous catheter, Pediatric Index of Mortality-2 score, and timing of antibiotics and IV fluids (adjusted odds ratio, 4.2; 95% CI, 1.7–10.4).

Conclusions:

Use of a protocolized emergency department sepsis guideline was independently associated with resolution of organ dysfunction by hospital day 2 compared to nonprotocolized usual care. These data indicate that morbidity outcomes in children can be improved with the use of protocolized care.
Disaster Preparedness Medical School Elective
Authors: Patel Vishnu M. , Dahl-Grove Deanna
Published: July 2016

Objective

Eager medical students may not be prepared for unanticipated complexities of disaster response. This study aimed to answer 2 questions: does an online disaster preparedness curriculum create a convenient method to educate medical students and motivate them to be better prepared to volunteer?

Methods

An online disaster preparedness elective was created for medical students. Four modules were created using Softchalk and hosted on the Blackboard Learning Management System. Students completed embedded pre-elective, post-lesson, and post-elective surveys.

Results

Fifty-five students completed the elective. When posed with the statement, “I feel prepared for an emergency at the University or the immediate area,” 70% stated that they disagreed or strongly disagreed before the elective. Subsequently, only 11% claimed to disagree after the elective. At the conclusion of the elective, 13% of students had prepared a personal emergency kit and 28% had prepared a family communication plan for reunification. Students were surveyed on the statement “I would like to be involved in a community disaster response while continuing my medical training.” Ninety-four percent claimed to agree or strongly agree before the elective, and 93% stated the same after elective completion.

Conclusions

This disaster preparedness elective was envisioned to be a resource for students. Advantages of online availability are ease of student access and minimal demand on faculty resources. A voluntary, self-paced online elective in disaster preparedness has shown to create a stronger interest in disaster participation in medical students. Student readiness to volunteer improved; however, willingness remained stagnant.
Capnography Use During Intubation and Cardiopulmonary Resuscitation in the Pediatric Emergency Department
Authors: Bullock Adam , Dodington James M. , Donoghue Aaron J. , Langhan Melissa L.
Published: July 2016

Objective

Capnography is indicated as a guide to assess and monitor both endotracheal intubation and cardiopulmonary resuscitation (CPR). Our primary objective was to determine the effect of the 2010 American Heart Association (AHA) guidelines on the frequency of capnography use during critical events in children in the emergency department (ED). Our secondary objective was to examine associations between patient characteristics and capnography use among these patients.

Methods

A retrospective chart review was performed on children aged 0 to 21 years who were intubated or received CPR in 2 academic children's hospital EDs between January 2009 and December 2012. Age, sex, time of arrival, medical or traumatic cause, length of CPR, return of spontaneous circulation (ROSC), documented use of capnography and colorimetry, capnography values, and adverse events were recorded.

Results

Two hundred ninety-two patients were identified and analyzed. Intubation occurred in 95% of cases and CPR in 30% of cases. Capnography was documented in only 38% of intubated patients and 13% of patients requiring CPR. There was an overall decrease in capnography use after publication of the 2010 AHA recommendations (P = 0.05). Capnography use was associated with a longer duration of CPR and return of spontaneous circulation.

Conclusions

Despite the 2010 AHA recommendations, a minority of critically ill children are being monitored with capnography and an unexpected decrease in documented use occurred among our sample. Further education and implementation of capnography should take place to improve the use of this monitoring device for critically ill pediatric patients in the ED.
Topographies of Cortical and Subcortical Volume Loss in HIV and Aging in the cART Era
Authors: Guha Anika , Brier Matthew R. , Ortega Mario , Westerhaus Elizabeth , Nelson Brittany , Ances Beau M.
Published: July 2016

Objectives:

Studies of HIV-associated brain atrophy often focus on a priori brain regions of interest, which can introduce bias. A data-driven, minimally biased approach was used to analyze changes in brain volumetrics associated with HIV and their relationship to aging, viral factors, combination antiretroviral therapy (cART), and gender, and smoking.

Design:

A cross-sectional study of 51 HIV-uninfected (HIV−) and 146 HIV-infected (HIV+) participants.

Methods:

Structural MRI of participants was analyzed using principal component analysis (PCA) to reduce dimensionality and determine topographies of volumetric changes. Neuropsychological (NP) assessment was examined using global and domain-specific scores. The effects of HIV disease factors (eg, viral load, CD4, etc.) on brain volumes and neuropsychological were investigated using penalized regression (LASSO).

Results:

Two components of interest were visualized using principal component analysis. An aging effect predominated for both components. The first component, a cortically weighted topography, accounted for a majority of variance across participants (43.5% of variance) and showed independent effects of HIV and smoking. A secondary, subcortically weighted topography (4.6%) showed HIV-status accentuated age-related volume loss. In HIV+ patients, the cortical topography correlated with global neuropsychological scores and nadir CD4, whereas subcortical volume loss was associated with recent viral load.

Conclusions:

Cortical regions showed the most prominent volumetric changes because of aging and HIV. Within HIV+ participants, cortical volumes were associated with immune history, whereas subcortical changes correlated with current immune function. Cognitive function was primarily associated with cortical volume changes. Observed volumetric changes in chronic HIV+ patients may reflect both past infection history and current viral status.
Implementation and Operational Research: Evolution of Couples' Voluntary Counseling and Testing for HIV in Rwanda: From Research to Public Health Practice
Authors: Karita Etienne , Nsanzimana Sabin , Ndagije Felix , Wall Kristin M. , Mukamuyango Jeannine , Mugwaneza Placidie , Remera Eric , Raghunathan Pratima L. , Bayingana Roger , Kayitenkore Kayitesi , Bekan-Homawoo Brigitte , Tichacek Amanda , Allen Susan
Published: July 2016

Background:

Couples' voluntary HIV counseling and testing (CVCT) is a WHO-recommended intervention for prevention of heterosexual HIV transmission which very few African couples have received. We report the successful nationwide implementation of CVCT in Rwanda.

Methods:

From 1988 to 1994 in Rwanda, pregnant and postpartum women were tested for HIV and requested testing for their husbands. Partner testing was associated with more condom use and lower HIV and sexually transmitted infection rates, particularly among HIV-discordant couples. After the 1994 genocide, the research team continued to refine CVCT procedures in Zambia. These were reintroduced to Rwanda in 2001 and continually tested and improved. In 2003, the Government of Rwanda (GoR) established targets for partner testing among pregnant women, with the proportion rising from 16% in 2003 to 84% in 2008 as the prevention of mother-to-child transmission program expanded to >400 clinics. In 2009, the GoR adopted joint posttest counseling procedures, and in 2010 a quarterly follow-up program for discordant couples was established in government clinics with training and technical assistance. An estimated 80%–90% of Rwandan couples have now been jointly counseled and tested resulting in prevention of >70% of new HIV infections.

Conclusions:

Rwanda is the first African country to have established CVCT as standard of care in antenatal care. More than 20 countries have sent providers to Rwanda for CVCT training. To duplicate Rwanda's success, training and technical assistance must be part of a coordinated effort to set national targets, timelines, indicators, and budgets. Governments, bilateral, and multilateral funding agencies must jointly prioritize CVCT for prevention of new HIV infections.
Hepatitis E: prevention and treatment
Authors: Nelson Kenrad E. , Heaney Christopher D. , Labrique Alain B. , Kmush Brittany L. , Krain Lisa J.
Published: July 2016

Purpose of review

Infection with the hepatitis E virus (HEV) is very common worldwide. The epidemiology, viral genotypes, and transmission routes differ between low-resource countries and economically developed countries. These differences have resulted in the design of diverse prevention and treatment strategies to combat HEV.

Recent findings

The population seroprevalence of HEV immunoglobulin G varies between 5 and 50%. However, the diagnosis of acute hepatitis from HEV has not been common in the United States or Western Europe. Chronic progressive HEV infections have been reported among patients who are immunocompromised. Successful treatment of patients with chronic hepatitis from HEV infection with antiviral agents, such as ribavirin or interferon-α, has been reported. Extrahepatic manifestations of HEV infection are common. Large epidemics of hundreds or thousands of cases continue to be reported among populations in Asia and Africa. A subunit peptide HEV vaccine has been found to be highly efficacious in a large clinical trial. However, the vaccine has not been evaluated in populations of pregnant women or other risk groups and is only available in China.

Although HEV infections are increasingly recognized as a global public health problem, there are few methods for prevention and treatment that are widely available.
Next-generation sequencing approaches for the diagnosis of skeletal muscle disorders
Authors: Nigro Vincenzo , Savarese Marco
Published: July 2016

Purpose of review

The development of next-generation sequencing (NGS) technologies is transforming the practice of medical genetics and revolutionizing the approach to heterogeneous hereditary conditions, including skeletal muscle disorders. Here, we review the different NGS approaches described in the literature so far for the characterization of myopathic patients and the results obtained from the implementation of such approaches in a clinical setting.

Recent findings

The overall diagnostic rate of NGS strategies for patients affected by skeletal muscle disorders is higher than the success rate obtained using the traditional gene-by-gene approach. Moreover, many recent articles have been expanding the clinical phenotypes associated with already known disease genes.

NGS applications will soon be the first-tier test for skeletal muscle disorders. They will improve the diagnosis in myopathic patients, promoting their inclusion into novel therapeutic trials. At the same time, they will improve our knowledge about the molecular mechanisms causing skeletal muscle disorders, favoring the development of novel therapeutic approaches.
Asynchronicity of Organic and Psychiatric Symptoms in a Case of Sertraline Intoxication
Authors: Pitzianti Mariabernarda , Marciano Sara , Minnei Maurizio , Baratta Antonia , Pasini Augusto
Published: July 2016

Sertraline is a selective serotonin reuptake inhibitor used as an antidepressant and antipanic agent in children and adolescents. Sertraline is well tolerated and its safety profile in overdose is favorable. However, sertraline overdose may cause a toxic hyperserotonergic state known as serotonin syndrome (SS). Serotonin syndrome may be misdiagnosed in children because it has been reported mostly in adults. In the present case report, we describe a 16-year-old female patient who ingested 2000 mg of sertraline to attempt suicide. The patient showed symptoms and signs suggestive of SS, characterized by an asynchronicity between organic and psychiatric symptoms. In addition, the patient showed a variability of psychiatric symptoms through time. Thirteen hours after sertraline overdose, she was poorly cooperative with poverty of speech and marked emotional tension, but she was oriented in space and time and was able to remember what happened to her and to reconstruct the dynamics of the fact. Twenty-four hours after sertraline overdose, the patient developed a delusion of reference associated with intense anxiety and depressed mood. In the present case report, we discuss the pathophysiologic mechanisms of the observed clinical manifestations and propose an observation period for sertraline overdose in children and adolescents that is sufficiently long (at least 72 hours) even in the absence of unstable vital signs.
Premenstrual Dysphoric Disorder Without Comorbid Psychiatric Conditions: A Systematic Review of Therapeutic Options
Authors: Sepede Gianna , Sarchione Fabiola , Matarazzo Ilaria , Di Giannantonio Massimo , Salerno Rosa Maria
Published: July 2016

Objectives

Premenstrual dysphoric disorder (PMDD) is a disabling condition affecting approximately 2% to 8% of women during reproductive age. It has been recently included in the mood disorder section of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, but its treatment as a primary psychiatric illness is still debated, because of the high prevalence of other mental disturbances in PMDD patients. On the other hand, clear clinical guidelines for PMDD patients not suffering from comorbid mental conditions are not yet available. The aim of the present study was therefore to systematically review the original articles pertaining to the treatment of PMDD in adult women free of any current or previous psychiatric comorbidity.

Methods

We searched PubMed to identify published studies on PMDD, including randomized controlled trials, open-label trials, and case series or case reports involving adult women with no history of comorbid mental conditions. The search was conducted in April 2015.

Results

We found 55 studies fulfilling our inclusion criteria, 49 of them focused on pharmacological/chemical agents and the remaining 6 on nonpharmacological interventions.

Conclusions

Based on the results of our qualitative synthesis, the best therapeutic option in the treatment of adult PMDD patients free of other mental disorders are selective serotonin reuptake inhibitor antidepressants (especially paroxetine and fluoxetine) and low doses of oral estroprogestins. Other interventions, such as light therapy, cognitive behavioral therapy, food supplements, and herbal medicines, showed promising effects, but other investigations are needed to confirm their efficacy.
An Empirical Biomarker-based Calculator for Autosomal Recessive Polycystic Kidney Disease The Nieto-Narayan Formula
Authors: Nieto Jake A , Yamin Michael A , Goldberg Itzhak D. , Narayan Prakash
Published: July 2016

Autosomal polycystic kidney disease (ARPKD) is associated with progressive enlargement of the kidneys fuelled by the formation and expansion of fluid-filled cysts. The disease is congenital and children that do not succumb to it during the neonatal period will, by age 10 years, more often than not, require nephrectomy+renal replacement therapy for management of both pain and renal insufficiency. Since increasing cystic index (CI; percent of kidney occupied by cysts) drives both renal expansion and organ dysfunction, management of these patients, including decisions such as elective nephrectomy and prioritization on the transplant waitlist, could clearly benefit from serial determination of CI. So also, clinical trials in ARPKD evaluating efficacy of novel drug candidates could benefit from serial determination of CI. Although ultrasound is currently the imaging modality of choice for diagnosis of ARPKD, its utilization for assessing disease progression is highly limited. Magnetic resonance imaging or computed tomography, although more reliable for determination of CI, are expensive, time-consuming and somewhat impractical in the pediatric population. Using a well-established mammalian model of ARPKD, we undertook a big data-like analysis of minimally- or non-invasive serum and urine biomarkers of renal injury/dysfunction to derive a family of equations for estimating CI. We then applied a signal averaging protocol to distil these equations to a single empirical formula for calculation of CI. Such a formula will eventually find use in identifying and monitoring patients at high risk for progressing to end-stage renal disease and aid in the conduct of clinical trials.
Protection against maternal infection-associated fetal growth restriction - proof-of-concept with a microbial-derived immunomodulator OM85: safety and efficacy data
Authors: Scott NM , Lauzon-Joset JF , Jones AC , Mincham KT , Troy NM , Leffler J , Serralha M , Prescott SL , Robertson SA , Pasquali C , Bosco A , Holt PG , Strickland DH
Published: July 2016

Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction and/or miscarriage. Treatment strategies for protection of at-risk mothers are limited to a narrow range of vaccines, which do not cover the bulk of the common pathogens most frequently encountered. Employing mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85TM), currently used clinically for attenuation of infection-associated airway inflammatory symptoms in infants-adults, markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial LPS or influenza. Focusing on LPS exposure, we demonstrate that the key molecular indices of maternal inflammatory stress, notably high levels of RANTES, MIP-1a, CCL2, IL-8 and G-CSF in gestational tissues/serum, are abrogated by OM85 pretreatment. Systems-level analyses conducted in parallel employing RNASeq revealed that OM85 pretreatment selectively tunes LPS-induced activation in maternal gestational tissues for attenuated expression of TNF-, IL1-, and IFNg-driven that drive production of these pro-inflammatory cytokines, without constraining Type1-IFN-associated networks central to first-line anti-microbial defense. This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress, without compromising capacity for efficient pathogen eradication, represents an achievable therapeutic goal.

Disclosure

This study was funded principally by Nation Health and Medical Research Council (NHMRC) of Australia with supplementary support provided by OM Pharma (Geneva, Switzerland).

CP is an employee of OM Pharma (Vifor Pharma). The other authors declare that they have no conflict of interest.
The evolutionary origin of bilaterian smooth and striated myocytes
Authors: Brunet Thibaut , Fischer Antje H. L. , Steinmetz Patrick R. H. , Lauri Antonella , Bertucci Paola , Arendt Detlev
Published: July 2016

The dichotomy between smooth and striated myocytes is fundamental for bilaterian musculature, but its evolutionary origin is unsolved. In particular, interrelationships of visceral smooth muscles remain unclear. Absent in fly and nematode, they have not yet been characterized molecularly outside vertebrates. Here, we characterize expression profile, ultrastructure, contractility and innervation of the musculature in the marine annelid Platynereis dumerilii and identify smooth muscles around the midgut, hindgut and heart that resemble their vertebrate counterparts in molecular fingerprint, contraction speed, and nervous control. Our data suggest that both visceral smooth and somatic striated myocytes were present in the protostome-deuterostome ancestor, and that smooth myocytes later co-opted the striated contractile module repeatedly – for example in vertebrate heart evolution. During these smooth-to-striated myocyte conversions the core regulatory complex of transcription factors conveying myocyte identity remained unchanged, reflecting a general principle in cell type evolution.
On numerical study of Parkinson tremor
Authors: Harikrishna Annalakshmi , Osei Dennis Effah , Kamińska Magdalena Weronika , Majumdar Sarangam
Published: July 2016

Parkinson’s disease and Parkinson’s tremor are the two most common movement disorders, nor do we fully understand the origin of one of the disease’s cardinal symptom: the Parkinsonian tremor. We study one mathematical model involved in Parkinson’s disease and in the Parkinsonian tremor. In this paper, we use the Van der Pol equation to further understand this tremor as well as investigate different numerical approaches to solve the system and compare them.

AMS Subject Classification34L16; 34K28; 92B05