bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic Drug-Drug Interactions of Mood Stabilizers and Risperidone in Patients Under Combined Treatment
Authors: Schoretsanitis Georgios , Haen Ekkehard , Gründer Gerhard , Stegmann Benedikt , Schruers Koen R. J. , Hiemke Christoph , Lammertz Sarah E. , Paulzen Michael
Published: October 2016

Background

The combination of anticonvulsant mood stabilizers with antipsychotic drugs may lead to clinically relevant drug-drug interactions. The objective of the study was to identify pharmacokinetic interactions of different mood stabilizers on the metabolism of risperidone (RIS) under natural conditions.

Methods

A large therapeutic drug monitoring database containing plasma concentrations of RIS and its metabolite 9-hydroxy-RIS (9-OH-RIS) of 1,584 adult patients was analyzed. Four groups (n = 1,072) were compared: a control group without a potentially cytochrome interacting comedication (R0, n = 852), a group comedicated with valproate (VPA) (RVPA, n = 153), a group comedicated with lamotrigine (LMT) (RLMT, n = 46), and a group under concomitant medication with carbamazepine (CBZ) (RCBZ, n = 21). Dose-adjusted plasma concentrations (C/D ratio) for RIS, 9-OH-RIS and active moiety (AM) (RIS + 9-OH-RIS), as well as metabolic ratios (RIS/9-OH-RIS) were computed.

Results

Groups did not differ with regard to the daily dosage (P = 0.46). Differences were detected for the distributions of the C/D ratios for RIS, 9-OH-RIS and AM (P = 0.003, P < 0.001 and P < 0.001, respectively). Differences remained significant after conducting a Bonferroni correction (P = 0.0125). Pairwise comparisons of the concomitant medication groups with the control group revealed significant differences; RIS C/D ratios were significantly higher in the VPA and the LMT group than in the control group (P = 0.013; P = 0.021). However, these differences did not remain significant after Bonferroni correction. In contrast, CBZ-treated patients showed lower dose-adjusted plasma concentrations of 9-OH-RIS (P < 0.001) as well as the AM (P < 0.001) than the control group; this difference survived the Bonferroni correction.

Conclusions

The data give evidence for pharmacokinetic interactions between RIS and different anticonvulsant mood stabilizers. Carbamazepine decreased serum concentrations of 9-OH-RIS and the AM when compared with the control group. In case of VPA and LMT, findings were less significant; hints for a weak RIS metabolism inhibition by LMT of unclear clinical significance were found.
Postapproval Outcomes: The Berlin Heart EXCOR Pediatric in North America
Authors: Jaquiss Robert D. B. , Humpl Tilman , Canter Charles E. , Morales David L. S. , Rosenthal David N. , Fraser Charles D.
Published: October 2016

The Berlin Heart EXCOR Pediatric Ventricular Assist Device (BH) was approved for use in the United States in December 2011, based on a prospective investigational device exemption (IDE) trial. Strict exclusion criteria for the trial selected a low-risk “ideal” cohort. We sought to determine whether postapproval usage of the BH in a “real world” cohort of recipients would result in similar outcomes. Preimplant diagnostic information was collected for all patients. Efficacy was evaluated by comparison of all children (efficacy group, n = 247) implanted between FDA approval and April 2015 to those in the IDE trial (IDE, n = 48), with regard to achievement of one of four end-states: transplanted, successful weaning, death/unsuccessful weaning, or still-on-device. Safety outcomes were compared between IDE patients and a subset of postapproval patients (safety group, n = 39) for whom adjudicated adverse events were tracked in a regulator-mandated dataset. Diagnostic categories were similar between groups: IDE (congenital 19%, dilated cardiomyopathy/myocarditis/other 81%) versus Efficacy Group (congenital 24%, dilated cardiomyopathy/myocarditis/other 75%). Patients in the IDE cohort were larger (median 14.8 kg, range 3.6–58.1 kg vs. 10.7 kg, 2.9–112.0 kg, p = 0.02). More IDE patients were successfully supported than in the efficacy group cohort (90% vs. 77%, p = 0.05). Proportions with bleeding and stroke were similar between the IDE and safety group cohorts (46% vs. 41%, p = 0.65; 29% vs. 33%, p = 0.68, respectively). With usage of the BH in a less-ideal population, rates of bridge to transplant and weaning have declined slightly, but remain encouragingly high. Bleeding and neurologic event rates have not increased.
Oropharyngeal Dysphagia Is Strongly Correlated With Apparent Life‐Threatening Events
Authors: Duncan Daniel R. , Amirault Janine , Mitchell Paul D. , Larson Kara , Rosen Rachel L.
Published: October 2016

Objectives:

The aim of the present study was to investigate the prevalence of oropharyngeal dysfunction with resultant aspiration in patients admitted after apparent life‐threatening events (ALTE) and to determine whether historical characteristics could predict this oropharyngeal dysphagia and aspiration risk.

Methods:

We retrospectively reviewed the records of all patients admitted to Boston Children's Hospital between 2012 and 2015 with a diagnosis of ALTE to determine the frequency of evaluation for oropharyngeal dysphagia using video fluoroscopic swallow studies (VFSS) and clinical feeding evaluations, to determine the prevalence of swallowing dysfunction in subjects admitted after ALTE and to compare presenting historical characteristics to swallow study results.

Results:

A total of 188 children were admitted with a diagnosis of ALTE of which 29% (n = 55) had an assessment of swallowing by VFSS. Of those who had a VFSS, 73% (n = 40) had evidence of aspiration or penetration on VFSS. Of all of the diagnostic tests ordered on patients with ALTEs, the VFSS had the highest rate of abnormalities of any test ordered. None of the historical characteristics of ALTE predicted which patients were at risk for aspiration. In patients who had both clinical feeding evaluations and VFSS, observed clinical feedings incorrectly identified 26% of patients as having no oropharyngeal dysphagia when in fact aspiration was present on VFSS.

Conclusions:

Oropharyngeal dysphagia with aspiration is the most common diagnosis identified in infants presenting with ALTEs. The algorithm for ALTE should be revised to include an assessment of VFSS as clinical feeding evaluations are inadequate to assess for aspiration.
Inner Speech and Clarity of Self-Concept in Thought Disorder and Auditory-Verbal Hallucinations
Authors: de Sousa Paulo , Sellwood William , Spray Amy , Fernyhough Charles , Bentall Richard P.
Published: October 2016

Eighty patients and thirty controls were interviewed using one interview that promoted personal disclosure and another about everyday topics. Speech was scored using the Thought, Language and Communication scale (TLC). All participants completed the Self-Concept Clarity Scale (SCCS) and the Varieties of Inner Speech Questionnaire (VISQ). Patients scored lower than comparisons on the SCCS. Low scores were associated the disorganized dimension of TD. Patients also scored significantly higher on condensed and other people in inner speech, but not on dialogical or evaluative inner speech. The poverty of speech dimension of TD was associated with less dialogical inner speech, other people in inner speech, and less evaluative inner speech. Hallucinations were significantly associated with more other people in inner speech and evaluative inner speech. Clarity of self-concept and qualities of inner speech are differentially associated with dimensions of TD. The findings also support inner speech models of hallucinations.
Integrating Telepresence Robots Into Nursing Simulation
Authors: Rudolph Alexandra , Vaughn Jacqueline , Crego Nancy , Hueckel Remi , Kuszajewski Michele , Molloy Margory , Brisson Raymond , Shaw Ryan J.
Published: October 2016

This article provides an overview of the use of telepresence robots in clinical practice and describes an evaluation of an educational project in which distance-based nurse practitioner students used telepresence robots in clinical simulations with on-campus Accelerated Bachelor of Science in Nursing students. The results of this project suggest that the incorporation of telepresence in simulation is an effective method to promote engagement, satisfaction, and self-confidence in learning.
Prevalence and Correlates of Genital Infections Among Newly Diagnosed Human Immunodeficiency Virus–Infected Adults Entering Human Immunodeficiency Virus Care in Windhoek, Namibia
Authors: Djomand Gaston , Schlefer Madeleine , Gutreuter Steve , Tobias Sarah , Patel Roopal , DeLuca Nickolas , Hood Julia , Sawadogo Souleymane , Chen Cheng , Muadinohamba Alexinah , Lowrance David W. , Bock Naomi
Published: October 2016

Background

Identifying and treating genital infections, including sexually transmitted infections (STI), among newly diagnosed human immunodeficiency virus (HIV)-infected individuals may benefit both public and individual health. We assessed prevalence of genital infections and their correlates among newly diagnosed HIV-infected individuals enrolling in HIV care services in Namibia.

Methods

Newly diagnosed HIV-infected adults entering HIV care at 2 health facilities in Windhoek, Namibia, were recruited from December 2012 to March 2014. Participants provided behavioral and clinical data including CD4+ T lymphocyte counts. Genital and blood specimens were tested for gonorrhea, Chlamydia, trichomoniasis, Mycoplasma genitalium, syphilis, bacterial vaginosis, and vulvovaginal candidiasis.

Results

Among 599 adults, 56% were women and 15% reported consistent use of condoms in the past 6 months. The most common infections were bacterial vaginosis (37.2%), trichomoniasis (34.6%) and Chlamydia (14.6%) in women and M. genitalium (11.4%) in men. Correlates for trichomoniasis included being female (adjusted relative risk, [aRR], 7.18; 95% confidence interval [CI], 4.07–12.65), higher education (aRR, 0.58; 95% CI, 0.38–0.89), and lower CD4 cell count (aRR, 1.61; 95% CI, 1.08–2.40). Being female (aRR, 2.39; 95% CI, 1.27–4.50), nonmarried (aRR, 2.30; (95% CI, 1.28–4.14), and having condomless sex (aRR, 2.72; 95% CI, 1.06–7.00) were independently associated with chlamydial infection. Across all infections, female (aRR, 2.31; 95% CI, 1.79–2.98), nonmarried participants (aRR, 1.29; 95% CI, 1.06–1.59), had higher risk to present with any STI, whereas pregnant women (aRR, 1.16, 95% CI 1.03–1.31) were at increased risk of any STI or reproductive tract infection.
Implementation of Preexposure Prophylaxis for Human Immunodeficiency Virus Prevention Among Men Who Have Sex With Men at a New England Sexually Transmitted Diseases Clinic
Authors: Chan Philip A. , Glynn Tiffany R. , Oldenburg Catherine E. , Montgomery Madeline C. , Robinette Ashley E. , Almonte Alexi , Raifman Julia , Mena Leandro , Patel Rupa , Mayer Kenneth H. , Beauchamps Laura S. , Nunn Amy S.
Published: October 2016

Background

Preexposure prophylaxis (PrEP) is efficacious in preventing human immunodeficiency virus (HIV) among men who have sex with men (MSM). We assessed PrEP uptake among MSM presenting for services at a sexually transmitted diseases (STD) clinic.

Methods

Men who have sex with men presenting to the Rhode Island STD Clinic between October 2013 and November 2014 were educated about, and offered, PrEP. We categorized PrEP engagement using an implementation cascade to describe gaps in uptake which described MSM who: (1) were educated about PrEP, (2) indicated interest, (3) successfully received follow-up contact, (4) scheduled an appointment, (5) attended an appointment, and (6) initiated PrEP (ie, received a prescription). Bivariate and multivariable logistic regression models were used to examine predictors of PrEP initiation.

Results

A total of 234 MSM were educated about PrEP; of these, 56% expressed interest. Common reasons for lack of interest were low HIV risk perception (37%), wanting more time to consider (10%), concern about side effects (7%), and financial barriers (3%). Among those interested, 53% followed up. Of those, 51% scheduled an appointment. The most common reason patients did not schedule an appointment was low HIV risk perception (38%). Seventy-seven percent of those with an appointment attended the appointment; of those, 93% initiated PrEP. Patients with higher HIV-risk perception (adjusted odds ratios, 2.17; 95% confidence interval, 1.29–3.64) and a history of sex with an HIV-positive partner (adjusted odds ratios, 7.08; 95% confidence interval, 2.35–21.34) had significantly higher odds of initiating PrEP.

Conclusions

Low HIV-risk perception was the most significant barrier to PrEP uptake among MSM attending a public STD clinic.
Reducing Missed Opportunities: Pairing Sexually Transmitted Infection Screening With Syringe Exchange Services
Authors: Roth Alexis M. , Goldshear Jesse L. , Martinez-Donate Ana P. , Welles Seth , Chavis Martha , Van Der Pol Barbara
Published: October 2016

About 17.5% of sexually active injection drug users recruited from a syringe exchange in Camden, NJ (n = 120) screened positive for chlamydia/gonorrhea. Among these cases, 40% were detected via extragenital screening. This pilot demonstrates that colocating sexually transmitted infection control with syringe exchange leads to sexually transmitted infection case finding.
Young Low-Risk Heterosexual Clients Prefer a Chlamydia Home Collection Test to a Sexually Transmitted Infection Clinic Visit in Amsterdam, the Netherlands, A Cross-Sectional Study
Authors: van Rooijen Martijn S. , Koekenbier Rik H. , Hendriks Alfons , de Vries Henry J.C. , van Leeuwen Petra , van Veen Maaike G.
Published: October 2016

Background

Home-based self-collection of specimens for urogenital and anorectal chlamydia testing has been proven feasible and acceptable. We studied the efficiency of chlamydia home collection kits for young low-risk persons to optimize care at the Amsterdam sexually transmitted infection (STI) clinic.

Methods

Low-risk heterosexual persons under 25 years submitting an appointment request online were offered 3 different ways of chlamydia testing: (1) receiving a home collection kit, (2) coming to the clinic without, or (3) with sexual health counseling. The collection kit was sent to the client by surface mail and was used to self-collect a vaginal swab or urine sample (men). This sample was sent back to the laboratory for testing and the results could be retrieved online. Testing for gonorrhea, syphilis, and human immunodeficiency virus was indicated after testing chlamydia-positive.

Results

Between September 2012 until July 2013, from 1804 online requests, 1451 (80%) opted for the home collection kit, 321 (18%) preferred an appointment at the clinic without, and 32 (2%) with sexual health counseling. Of the requested home collection kits, 88% were returned. Chlamydia was diagnosed in 6.0% of the clients receiving a home collection kit, and none of the chlamydia-positive clients tested positive for other STI.

Conclusions

Home collection is the preferred method for most young low-risk heterosexual clients who seek STI care. With a high compliance to collect and return the samples, home collection can be used as a tool to increase efficiency and dedicate STI clinic workers efforts to those at highest risk.
Google Glass for Residents Dealing With Pediatric Cardiopulmonary Arrest: A Randomized, Controlled, Simulation-Based Study
Authors: Drummond David , Arnaud Cécile , Guedj Romain , Duguet Alexandre , de Suremain Nathalie , Petit Arnaud
Published: October 2016

Objectives:

To determine whether real-time video communication between the first responder and a remote intensivist via Google Glass improves the management of a simulated in-hospital pediatric cardiopulmonary arrest before the arrival of the ICU team.

Design:

Randomized controlled study.

Setting:

Children’s hospital at a tertiary care academic medical center.

Subjects:

Forty-two first-year pediatric residents.

Interventions:

Pediatric residents were evaluated during two consecutive simulated pediatric cardiopulmonary arrests with a high-fidelity manikin. During the second evaluation, the residents in the Google Glass group were allowed to seek help from a remote intensivist at any time by activating real-time video communication. The residents in the control group were asked to provide usual care.

Measurements and Main Results:

The main outcome measures were the proportion of time for which the manikin received no ventilation (no-blow fraction) or no compression (no-flow fraction). In the first evaluation, overall no-blow and no-flow fractions were 74% and 95%, respectively. During the second evaluation, no-blow and no-flow fractions were similar between the two groups. Insufflations were more effective (p = 0.04), and the technique (p = 0.02) and rate (p < 0.001) of chest compression were more appropriate in the Google Glass group than in the control group.

Conclusions:

Real-time video communication between the first responder and a remote intensivist through Google Glass did not decrease no-blow and no-flow fractions during the first 5 minutes of a simulated pediatric cardiopulmonary arrest but improved the quality of the insufflations and chest compressions provided.
An Elevated Low Cardiac Output Syndrome Score Is Associated With Morbidity in Infants After Congenital Heart Surgery*
Authors: Ulate Kalia P. , Yanay Ofer , Jeffries Howard , Baden Harris , Di Gennaro Jane L. , Zimmerman Jerry
Published: October 2016

Objectives:

To evaluate an empirically derived Low Cardiac Output Syndrome Score as a clinical assessment tool for the presence and severity of Low Cardiac Output Syndrome and to examine its association with clinical outcomes in infants who underwent surgical repair or palliation of congenital heart defects.

Design:

Prospective observational cohort study.

Setting:

Cardiac ICU at Seattle Children’s Hospital.

Patients:

Infants undergoing surgical repair or palliation of congenital heart defects.

Interventions:

None.

Measurements and Main Results:

Clinical and laboratory data were recorded hourly for the first 24 hours after surgery. A Low Cardiac Output Syndrome Score was calculated by assigning one point for each of the following: tachycardia, oliguria, toe temperature less than 30°C, need for volume administration in excess of 30 mL/kg/d, decreased near infrared spectrometry measurements, hyperlactatemia, and need for vasoactive/inotropes in excess of milrinone at 0.5 μg/kg/min. A cumulative Low Cardiac Output Syndrome Score was determined by summation of Low Cardiac Output Syndrome Score on arrival to cardiac ICU, and 8, 12, and 24 hours postoperatively. Scores were analyzed for association with composite morbidity (prolonged mechanical ventilation, new infection, cardiopulmonary arrest, neurologic event, renal dysfunction, necrotizing enterocolitis, and extracorporeal life support) and resource utilization. Fifty-four patients were included. Overall composite morbidity was 33.3%. Median peak Low Cardiac Output Syndrome Score and cumulative Low Cardiac Output Syndrome Score were higher in patients with composite morbidity (3 [2–5] vs 2 [1–3]; p = 0.003 and 8 [5–10] vs 2.5 [1–5]; p < 0.001)]. Area under the receiver operating characteristic curve for cumulative Low Cardiac Output Syndrome Score versus composite morbidity was 0.83, optimal cutoff of greater than 6. Patients with cumulative Low Cardiac Output Syndrome Score greater than or equal to 7 had higher morbidity, longer duration of mechanical ventilation, cardiac ICU, and hospital length of stay (all p ≤ 0.001). After adjusting for other relevant variables, peak Low Cardiac Output Syndrome Score and cumulative Low Cardiac Output Syndrome Score were independently associated with composite morbidity (odds ratio, 2.57; 95% CI, 1.12–5.9 and odds ratio, 1.35; 95% CI, 1.09–1.67, respectively).

Conclusion:

Higher peak Low Cardiac Output Syndrome Score and cumulative Low Cardiac Output Syndrome Score were associated with increased morbidity and resource utilization among infants following surgery for congenital heart defects and might be a useful tools in future cardiac intensive care research. Independent validation is required.
Neurally Adjusted Ventilatory Assist in Preterm Infants With Established or Evolving Bronchopulmonary Dysplasia on High-Intensity Mechanical Ventilatory Support: A Single-Center Experience
Authors: Jung Young Hwa , Kim Han-Suk , Lee Juyoung , Shin Seung Han , Kim Ee-Kyung , Choi Jung-Hwan
Published: October 2016

Objectives:

The aim of the present study was to report possible improvements in ventilator variables associated with a transition from synchronized intermittent mandatory ventilation to neurally adjusted ventilatory assist in preterm infants with bronchopulmonary dysplasia who required a high level of mechanical ventilatory support in a single center.

Design:

Retrospective study.

Setting:

Neonatal ICU.

Patients:

Twenty-nine preterm infants with a median gestational age of 25.4 weeks (range, 23.4–30.3 wk) and a median birth weight of 680 g (range, 370–1,230 g) and who were supported with a mechanical ventilator for more than 4 weeks and had a respiratory severity score greater than four during conventional mechanical ventilation prior to conversion to neurally adjusted ventilatory assist.

Interventions:

Comparison of ventilatory variables, work of breathing, and blood gas values during conventional ventilation and at various time intervals after the change to neurally adjusted ventilatory assist.

Measurements and Main Results:

The values of various ventilatory variables and other measurements were obtained 1 hour before neurally adjusted ventilatory assist and 1, 4, 12, and 24 hours after conversion to neurally adjusted ventilatory assist. During neurally adjusted ventilatory assist, the peak inspiratory pressure (20.12 ± 2.93 vs 14.15 ± 3.55 cm H2O; p < 0.05), mean airway pressure (11.15 ± 1.29 vs 9.57 ± 1.27 cm H2O; p < 0.05), and work of breathing (0.86 ± 0.22 vs 0.46 ± 0.12 J/L; p < 0.05) were significantly decreased, and the blood gas values were significantly improved. Significantly lower Fio
2 and improved oxygen saturation were observed during neurally adjusted ventilatory assist compared with conventional ventilation support. The RSS values decreased and sustained during neurally adjusted ventilatory assist (4.85 ± 1.63 vs 3.21 ± 1.01; p < 0.001).

Conclusions:

The transition from synchronized intermittent mandatory ventilation to neurally adjusted ventilatory assist ventilation was associated with improvements in ventilator variables, oxygen saturation, and blood gas values in infants with bronchopulmonary dysplasia in a single center. This study suggests the possible clinical utility of neurally adjusted ventilatory assist as a weaning modality for bronchopulmonary dysplasia patients in the neonatal ICU.
PICU Up!: Impact of a Quality Improvement Intervention to Promote Early Mobilization in Critically Ill Children*
Authors: Wieczorek Beth , Ascenzi Judith , Kim Yun , Lenker Hallie , Potter Caroline , Shata Nehal J. , Mitchell Lauren , Haut Catherine , Berkowitz Ivor , Pidcock Frank , Hoch Jeannine , Malamed Connie , Kravitz Tamara , Kudchadkar Sapna R.
Published: October 2016

Objective:

To determine the safety and feasibility of an early mobilization program in a PICU.

Design:

Observational, pre-post design.

Setting:

PICU in a tertiary academic hospital in the United States.

Patients:

Critically ill pediatric patients admitted to the PICU.

Intervention:

This quality improvement project involved a usual-care baseline phase, followed by a quality improvement phase that implemented a multicomponent, interdisciplinary, and tiered activity plan to promote early mobilization of critically ill children.

Measurements and Main Results:

Data were collected and analyzed from July to August 2014 (preimplementation phase) and July to August 2015 (postimplementation). The study sample included 200 children 1 day through 17 years old who were admitted to the PICU and had a length of stay of at least 3 days. PICU Up! implementation led to an increase in occupational therapy consultations (44% vs 59%; p = 0.034) and physical therapy consultations (54% vs 66%; p = 0.08) by PICU day 3. The median number of mobilizations per patient by PICU day 3 increased from 3 to 6 (p < 0.001). More children engaged in mobilization activities after the PICU Up! intervention by PICU day 3, including active bed positioning (p < 0.001), and ambulation (p = 0.04). No adverse events occurred as a result of early mobilization activities. The most commonly reported barriers to early mobilization after PICU Up! implementation was availability of appropriate equipment. The program was positively received by PICU staff.

Conclusions:

Implementation of a structured and stratified early mobilization program in the PICU was feasible and resulted in no adverse events. PICU Up! increased physical therapy and occupational therapy involvement in the children’s care and increased early mobilization activities, including ambulation. A bundled intervention to create a healing environment in the PICU with structured activity may have benefits for short- and long-term outcomes of critically ill children.
Autogenous Bone Reconstruction of Large Secondary Skull Defects
Authors: Fearon Jeffrey A. , Griner Devan , Ditthakasem Kanlaya , Herbert Morley
Published: October 2016

Background:

The authors sought to ascertain the upper limits of secondary skull defect size amenable to autogenous reconstructions and to examine outcomes of a surgical series. Published data for autogenous and alloplastic skull reconstructions were also examined to explore associations that might guide treatment.

Methods:

A retrospective review of autogenously reconstructed secondary skull defects was undertaken. A structured literature review was also performed to assess potential differences in reported outcomes between autogenous bone and synthetic alloplastic skull reconstructions. Weighted risks were calculated for statistical testing.

Results:

Ninety-six patients underwent autogenous skull reconstruction for an average defect size of 93 cm2 (range, 4 to 506 cm2) at a mean age of 12.9 years. The mean operative time was 3.4 hours, 2 percent required allogeneic blood transfusions, and the average length of stay was less than 3 days. The mean length of follow-up was 28 months. There were no postoperative infections requiring surgery, but one patient underwent secondary grafting for partial bone resorption. An analysis of 34 studies revealed that complications, infections, and reoperations were more commonly reported with alloplastic than with autogenous reconstructions (relative risk, 1.57, 4.8, and 1.48, respectively).

Conclusions:

Autogenous reconstructions are feasible, with minimal associated morbidity, for patients with skull defect sizes as large as 500 cm2. A structured literature review suggests that autogenous bone reconstructions are associated with lower reported infection, complication, and reoperation rates compared with synthetic alloplasts. Based on these findings, surgeons might consider using autogenous reconstructions even for larger skull defects.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Calf Perforator Flaps: A Freestyle Solution for Oral Cavity Reconstruction
Authors: Molina Alexandra R. , Citron Isabelle , Chinaka Fungayi , Cascarini Luke , Townley William A.
Published: October 2016

Background:

Reconstruction of oral cavity defects requires a thin, pliable flap for optimal functional results. Traditional flap choices are imperfect: the anterolateral thigh flap is excessively thick, whereas the radial forearm flap has a poor donor site. The authors therefore favor calf perforator flaps such as the medial sural artery perforator flap to provide thin tissue with an acceptable donor site. This two-part study aims to demonstrate their suitability for intraoral reconstruction.

Methods:

In the radiologic part of the study, the authors compared thigh and calf tissue thickness by examining lower limb computed tomographic scans of 100 legs. For their clinical study, they collected data prospectively on 20 cases of oral cavity reconstruction using calf perforator flaps.

Results:

The mean thickness of the calf tissue envelope was significantly less than that of the thigh (8.4 mm compared with 17 mm) based on computed tomographic analysis. In the clinical study, a medial sural artery perforator was used in the majority of cases (17 of 20). The mean pedicle length was 10.2 cm and the mean time to raise a flap was 85 minutes. There were no flap losses. One patient was returned to the operating room for management of late hematoma and wound dehiscence.

Conclusions:

Calf perforator flaps provide ideal tissue for intraoral reconstruction and are significantly thinner than anterolateral thigh flaps. In addition to medial sural artery perforator flaps, the authors raised both sural and soleal artery perforator flaps in this series. Opportunistic use of the calf donor site allows the harvest of thin tissue with minimal donor-site morbidity.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Striking a Better Integration of Work and Life: Challenges and Solutions
Authors: Cheesborough Jennifer E. , Gray Sylvia S. , Bajaj Anureet K.
Published: October 2016

Plastic surgeons are a diverse group but share a drive for excellence and dedication to their patients and the advancement of the specialty. Long hours at work and the need to be on call have limited the time that many have to spend on activities outside of the workplace. Reconciliation of the demands of surgery and private life can at times seem impossible. A failure to achieve balance between work and home life is associated with reduced job and life satisfaction, impaired mental health, family conflict, and ultimately burnout. Although the obstacles are many and varied, the authors have attempted to identify the challenges and propose solutions. The authors focus on women in plastic surgery in this article, but acknowledge that these issues are not unique to women or plastic surgery.
The Modern Male Rhytidectomy: Lessons Learned
Authors: Rohrich Rod J. , Stuzin James M. , Ramanadham Smita , Costa Christopher , Dauwe Phillip B.
Published: October 2016

Background:

Cosmetic surgery among male patients has become increasingly popular. The face-lift technique is different in male patients, specifically regarding preservation of hair follicles, restoration of a youthful and well appearance, and reduction of the risk of hematoma.

Methods:

A retrospective review of a single surgeon’s past 20 years of consecutive male rhytidectomies revealed a cohort of 83 patients. A control group was created by random selection of 83 age-matched female rhytidectomy patients during the same period. Data were collected and analyzed critically for factors contributing to complications, including hematoma, seroma, skin sloughing, alopecia, infection, and nerve injury. The evolution in the senior author’s technique in male rhytidectomy is described.

Results:

Differences in facial analysis and rhytidectomy technique in male patients and female patients are highlighted. Five male patients (6.0 percent) and no female patients in the control group developed postoperative hematoma (p = 0.0587). No other complications occurred.

Conclusion:

Respecting the patterns of hair growth in incision design, avoiding damage to follicles during dissection, and exercising standard of care (especially avoidance of hypotensive anesthesia) in prevention of postoperative hematoma have delivered safe and consistently reproducible aesthetic outcomes and acceptable complication rates.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Sanativo Wound Healing Product Does Not Accelerate Reepithelialization in a Mouse Cutaneous Wound Healing Model
Authors: Marshall Clement D. , Hu Michael S. , Leavitt Tripp , Barnes Leandra A. , Cheung Alexander T. M. , Malhotra Samir , Lorenz H. Peter , Delp Scott L. , Quake Stephen R. , Longaker Michael T.
Published: October 2016

Background:

Sanativo is an over-the-counter Brazilian product derived from Amazon rainforest plant extract that is purported to improve the healing of skin wounds. Two experimental studies have shown accelerated closure of nonsplinted excisional wounds in rat models. However, these models allow for significant contraction of the wound and do not approximate healing in the tight skin of humans.

Methods:

Full-thickness excisional wounds were created on the dorsal skin of mice and were splinted with silicone rings, a model that forces the wound to heal by granulation and reepithelialization. Sanativo or a control solution was applied either daily or every other day to the wounds. Photographs were taken every other day, and the degree of reepithelialization of the wounds was determined.

Results:

With both daily and every-other-day applications, Sanativo delayed reepithelialization of the wounds. Average time to complete healing was faster with control solution versus Sanativo in the daily application group (9.4 versus 15.2 days; p < 0.0001) and the every-other-day application group (11 versus 13 days; p = 0.017). The size of visible scar at the last time point of the study was not significantly different between the groups, and no differences were found on histologic examination.

Conclusions:

Sanativo wound healing compound delayed wound reepithelialization in a mouse splinted excisional wound model that approximates human wound healing. The size of visible scar after complete healing was not improved with the application of Sanativo. These results should cast doubt on claims that this product can improve wound healing in humans.
Surgical Treatment of Neuromas Improves Patient-Reported Pain, Depression, and Quality of Life
Authors: Domeshek Leahthan F. , Krauss Emily M. , Snyder-Warwick Alison K. , Laurido-Soto Osvaldo , Hasak Jessica M. , Skolnick Gary B. , Novak Christine B. , Moore Amy M. , Mackinnon Susan E.
Published: October 2016

Background:

Surgical management of neuromas is difficult, with no consensus on the most effective surgical procedure to improve pain and quality of life. This study evaluated the surgical treatment of neuromas by neurectomy, crush, and proximal transposition on improvement in pain, depression, and quality of life.

Methods:

Patients who underwent neuroma excision and proximal transposition were evaluated. Preoperative and postoperative visual analogue scale scores for pain (worst and average), depression, and quality of life were assessed using linear regression, and means were compared using pairedttests. The Disabilities of the Arm, Shoulder, and Hand questionnaire score was calculated preoperatively and postoperatively for upper extremity neuroma patients. Patients with long-term follow-up were analyzed using repeated measures analysis of variance comparing preoperative, postoperative, and long-term visual analogue scale scores.

Results:

Seventy patients (37 with upper extremity neuromas and 33 with lower extremity neuromas) met inclusion criteria. Statistically significant improvements in visual analogue scale scores were demonstrated for all four patient-rated qualities (p< 0.01) independent of duration of initial clinical follow-up. The change in preoperative to postoperative visual analogue scale scores was related inversely to the severity of preoperative scores for pain and depression. Neuroma excision and proximal transposition were equally effective in treating lower and upper extremity neuromas. Upper extremity neuroma patients had a statistically significant improvement in Disabilities of the Arm, Shoulder, and Hand questionnaire scores after surgical treatment (p< 0.02).

Conclusions:

Surgical neurectomy, crush, and proximal nerve transposition significantly improved self-reported pain, depression, and quality-of-life scores. Surgical intervention is a viable treatment of neuroma pain and should be considered in patients with symptomatic neuromas refractory to nonoperative management.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Anthropogenic transport of species across native ranges: unpredictable genetic and evolutionary consequences
Authors: Hudson Jamie , Viard Frédérique , Roby Charlotte , Rius Marc
Published: October 2016

Human activities are responsible for the translocation of vast amounts of organisms, altering natural patterns of dispersal and gene flow. Most research to date has focused on the consequences of anthropogenic transportation of non-indigenous species within introduced ranges, with little research focusing on native species. Here, we compared genetic patterns of the sessile marine invertebrate,Ciona intestinalis, which has highly restricted dispersal capabilities. We collected individuals in a region of the species' native range where human activities that are known to facilitate the artificial spread of species are prevalent. Using microsatellite markers, we revealed highly dissimilar outcomes. First, we found low levels of genetic differentiation among sites separated by both short and large geographical distances, indicating the presence of anthropogenic transport of genotypes, and little influence of natural geographical barriers. Second, we found significant genetic differentiation in pairwise comparisons among certain sites, suggesting that other factors besides artificial transport (e.g. natural dispersal, premodern population structure) may be shaping genetic patterns. Taken together, we found dissimilar patterns of population structure in a highly urbanized region that could not be predicted by artificial transport alone. We conclude that anthropogenic activities alter genetic composition of native ranges, with unknown consequences for species' evolutionary trajectories.
Numerical algebraic geometry for model selection and its application to the life sciences
Authors: Gross Elizabeth , Davis Brent , Ho Kenneth L. , Bates Daniel J. , Harrington Heather A.
Published: October 2016

Researchers working with mathematical models are often confronted by the related problems of parameter estimation, model validation and model selection. These are all optimization problems, well known to be challenging due to nonlinearity, non-convexity and multiple local optima. Furthermore, the challenges are compounded when only partial data are available. Here, we consider polynomial models (e.g. mass-action chemical reaction networks at steady state) and describe a framework for their analysis based on optimization using numerical algebraic geometry. Specifically, we use probability-one polynomial homotopy continuation methods to compute all critical points of the objective function, then filter to recover the global optima. Our approach exploits the geometrical structures relating models and data, and we demonstrate its utility on examples from cell signalling, synthetic biology and epidemiology.
The influence of curvature on three-dimensional mineralized matrix formation under static and perfused conditions: an
in vitro
bioreactor model
Authors: Vetsch Jolanda R. , Müller Ralph , Hofmann Sandra
Published: October 2016

Bone remodelling is the continuous turnover of bone by resorption and formation. It is controlled by interstitial fluid flow sensed by osteocytes. The refilling of bone resorption sites has been shown to be curvature driven.
In vitro,
curvature influences tissue growth and cytoskeletal arrangements under static and perfused conditions. Nevertheless, this has only been demonstrated for non-mineralized tissue in limited three-dimensional volumes. This study aims at investigating the influence of three different channel curvatures (S, −2.00 mm
−1
; M, −1.33 mm
−1
; L, −0.67 mm
−1
) on mineralized tissue formation in three dimensions under static and perfused conditions. The ingrowth of mineralized tissue into the channels was dependent on curvature and was higher under perfusion (M and S channels). L channels were not closed in any group compared with partially (static) or fully (perfused) closed M and S channels. Mineralized tissue morphology was cortical-like in static samples and trabecular-like in perfused samples. Our results suggest that the three-dimensional
in vitro
model presented is not only able to reveal effects of curvature on mineralized tissue formation, but may be used as an
in vitro
model for critical size defects in trabecular or cortical bone.
Symmetry-breaking phase transitions in highly concentrated semen
Authors: Creppy Adama , Plouraboué Franck , Praud Olivier , Druart Xavier , Cazin Sébastien , Yu Hui , Degond Pierre
Published: October 2016

New experimental evidence of self-motion of a confined active suspension is presented. Depositing fresh semen sample in an annular shaped microfluidic chip leads to a spontaneous vortex state of the fluid at sufficiently large sperm concentration. The rotation occurs unpredictably clockwise or counterclockwise and is robust and stable. Furthermore, for highly active and concentrated semen, richer dynamics can occur such as self-sustained or damped rotation oscillations. Experimental results obtained with systematic dilution provide a clear evidence of a phase transition towards collective motion associated with local alignment of spermatozoa akin to the Vicsek model. A macroscopic theory based on previously derived self-organized hydrodynamics models is adapted to this context and provides predictions consistent with the observed stationary motion.
A new magnetic resonance-based technique for high-resolution quantification of amorphous and quasi-amorphous structures
Authors: Rafferty James , Farr Lance , James Tim , Chase David , Heinrich John , Brady Michael
Published: October 2016

We present a novel, high-resolution magnetic resonance technique, fine structure analysis (FSA) for the quantification and analysis of amorphous and quasi-amorphous biological structures. The one-dimensional technique is introduced mathematically and then applied to one simulated phantom, two physical phantoms and a set of
ex vivo
biological samples, scanned with interpoint spacings of 0.0038–0.195 mm and cross-sectional sizes of 3 × 3 or 5 × 5 mm. The simulated phantom and one of the physical phantoms consists of randomly arranged beads of known size in two and three dimensions, respectively. The second physical phantom was constructed by etching lines on Perspex. The
ex vivo
samples are human bone specimens. We show that for all three phantoms, the FSA technique is able to elucidate the average spacing of the structures present within each sample using structural spectroscopy, the smallest of which was 180 µm in size. We further show that in samples of trabecular bone, FSA is able to produce comparable results to micro-computed tomography, the current gold standard for measuring bone microstructure, but without the need for ionizing radiation. Many biological structures are too small to be captured by conventional, clinically deployed medical imaging techniques. FSA has the potential for use in the analysis of pathologies where such small-scale repeating structures are disrupted or their size, and spacing is otherwise altered.
Identifying the necrotic zone boundary in tumour spheroids with pair-correlation functions
Authors: Dini S. , Binder B. J. , Fischer S. C. , Mattheyer C. , Schmitz A. , Stelzer E. H. K. , Bean N. G. , Green J. E. F.
Published: October 2016

Automatic identification of the necrotic zone boundary is important in the assessment of treatments on
in vitro
tumour spheroids. This has been difficult especially when the difference in cell density between the necrotic and viable zones of a tumour spheroid is small. To help overcome this problem, we developed novel one-dimensional pair-correlation functions (PCFs) to provide quantitative estimates of the radial distance of the necrotic zone boundary from the centre of a tumour spheroid. We validate our approach on synthetic tumour spheroids in which the position of the necrotic zone boundary is known
a priori
. It is then applied to nine real tumour spheroids imaged with light sheet-based fluorescence microscopy. PCF estimates of the necrotic zone boundary are compared with those of a human expert and an existing standard computational method.
Identification of the critical residues responsible for differential reactivation of the triosephosphate isomerases of two trypanosomes
Authors: Rodríguez-Bolaños Monica , Cabrera Nallely , Perez-Montfort Ruy
Published: October 2016

The reactivation of triosephosphate isomerase (TIM) from unfolded monomers induced by guanidine hydrochloride involves different amino acids of its sequence in different stages of protein refolding. We describe a systematic mutagenesis method to find critical residues for certain physico-chemical properties of a protein. The two similar TIMs of
Trypanosoma brucei
and
Trypanosoma cruzi
have different reactivation velocities and efficiencies. We used a small number of chimeric enzymes, additive mutants and planned site-directed mutants to produce an enzyme from
T. brucei
with 13 mutations in its sequence, which reactivates fast and efficiently like wild-type (WT) TIM from
T. cruzi
, and another enzyme from
T. cruzi,
with 13 slightly altered mutations, which reactivated slowly and inefficiently like the WT TIM of
T. brucei
. Our method is a shorter alternative to random mutagenesis, saturation mutagenesis or directed evolution to find multiple amino acids critical for certain properties of proteins.
A model to identify urban traffic congestion hotspots in complex networks
Authors: Solé-Ribalta Albert , Gómez Sergio , Arenas Alex
Published: October 2016

The rapid growth of population in urban areas is jeopardizing the mobility and air quality worldwide. One of the most notable problems arising is that of traffic congestion. With the advent of technologies able to sense real-time data about cities, and its public distribution for analysis, we are in place to forecast scenarios valuable for improvement and control. Here, we propose an idealized model, based on the critical phenomena arising in complex networks, that allows to analytically predict congestion hotspots in urban environments. Results on real cities’ road networks, considering, in some experiments, real traffic data, show that the proposed model is capable of identifying susceptible junctions that might become hotspots if mobility demand increases.
Reconstructing the past: methods and techniques for the digital restoration of fossils
Authors: Lautenschlager Stephan
Published: October 2016

During fossilization, the remains of extinct organisms are subjected to taphonomic and diagenetic processes. As a result, fossils show a variety of preservational artefacts, which can range from small breaks and cracks, disarticulation and fragmentation, to the loss and deformation of skeletal structures and other hard parts. Such artefacts can present a considerable problem, as the preserved morphology of fossils often forms the basis for palaeontological research. Phylogenetic and taxonomic studies, inferences on appearance, ecology and behaviour and functional analyses of fossil organisms strongly rely on morphological information. As a consequence, the restoration of fossil morphology is often a necessary prerequisite for further analyses. Facilitated by recent computational advances, virtual reconstruction and restoration techniques offer versatile tools to restore the original morphology of fossils. Different methodological steps and approaches, as well as software are outlined and reviewed here, and advantages and disadvantages are discussed. Although the complexity of the restorative processes can introduce a degree of interpretation, digitally restored fossils can provide useful morphological information and can be used to obtain functional estimates. Additionally, the digital nature of the restored models can open up possibilities for education and outreach and further research.