bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune checkpoint inhibitor (anti-CTLA-4, anti-PD-1) therapy alone versus immune checkpoint inhibitor (anti-CTLA-4, anti-PD-1) therapy in combination with anti-RANKL denosumuab in malignant melanoma: a retrospective analysis at a tertiary care center
Authors: Afzal Muhammad Z. , Shirai Keisuke
Published: May 2018

Denosumab is a monoclonal antibody against RANK ligand with a role in the prevention of skeletal-related events and is also known to possess antitumor properties. In this retrospective review, we aim to evaluate the synergist effect of a combination therapy with immune checkpoint inhibitors and denosumab in malignant melanoma patients. Patients of 18 years of age or older with a diagnosis of malignant melanoma who have received immune checkpoint inhibitors and denosumab between June 2015 and May 2017 were divided into two cohorts: cohort A (immune checkpoint inhibitors only) and cohort B (immune checkpoint inhibitors and denosumab). Overall survival, progression-free survival, objective response rate, and safety analysis were performed. Stratified analysis based on metastatic (M) status was performed as well. Eleven (29.72%) out of 37 patients received immune checkpoint inhibitors and denosumab combination. Median overall survival in cohort B was 57 months compared with 22.8 months in cohort A and 22 months in M1c patients from cohort A. Median progression-free survival was 4.15 months in cohort B compared with 11.6 months in cohort A and 5.12 months in M1c patients from cohort A. The mean number of distant sites involved in metastasis were significantly higher in cohort B (3.54 vs. 2.23, P=0.0015). Cohort B also had more patients with more than two distant metastatic sites (90.9 vs. 30.8%, P=0.001). A combination therapy with denosumab and immune checkpoint inhibitors may have a beneficial effect on survival and progression as in our study; the patients receiving combination therapy did not behave poorly despite having poor prognostic features.
Bowen Disease With Sebaceous Differentiation: A Case Report and Immunohistochemical Analysis of Adipophilin and Cytokeratin 1
Authors: Namiki Takeshi , Miura Keiko , Yokozeki Hiroo , Ansai Shin-ichi
Published: May 2018

Bowen disease with sebaceous differentiation has been rarely documented to date. Here, we present a case of Bowen disease with sebaceous differentiation. A 67-year-old man presented with a 6.0 × 3.5 cm erythematous plaque adjacent to a 7.0 × 3.0 cm erythematous plaque on his left abdomen. Dermoscopy revealed yellow structureless areas and dotted vessels on a pink homogenous background in addition to surface scales. Histopathological examination of the upper erythematous plaque showed parakeratosis and acanthosis with proliferation of atypical keratinocytes in the epidermis. Some of the atypical cells had large and hyperchromatic nuclei. Histopathological examination of the lower erythematous plaque showed tumor nests extending from the epidermis. Tumor nests with hyperchromatic and atypical cells had vacuolated cells. The diagnosis of Bowen disease with sebaceous differentiation was made. Immunohistochemistry revealed a positive reaction for cytokeratin 1 (CK1) in tumor cells of Bowen disease and a negative reaction for CK1 in tumor cells with the sebaceous differentiation, whereas immunohistochemistry revealed no apparent adipophilin-positive granules in tumor nests of Bowen disease compared with the prominent staining of adipophilin in tumor nests with sebaceous differentiation. We show Bowen disease with sebaceous differentiation taking advantage of immunohistochemistry of adipophilin and CK1. Those findings of Bowen disease with sebaceous differentiation may deepen our understandings and insights into the pathogenesis of sebaceous carcinoma and Bowen disease.
Raising Children with Autism Spectrum Disorders in Monolingual vs Bilingual Homes: A Scoping Review
Authors: Wang Michelle , Jegathesan Thivia , Young Elizabeth , Huber Joelene , Minhas Ripudaman
Published: May 2018

Background:

Approximately 20% of children in Canada and the United States are raised in bilingual family homes. Current recommendations for typically developing children are to encourage and support bilingual exposure in the home; however, there are no specific guidelines for families of children with autism spectrum disorders (ASDs), a disorder in which communication deficits are considered a hallmark feature.

Objective:

The aim of this study is to present a scoping review of studies that compare cognitive, linguistic, and behavioral outcomes for children with ASDs raised in monolingual vs bilingual homes.

Methods:

A systematic search of 6 databases for peer-reviewed literature and gray literature search through dissertation databases, conference archives, and reference lists of pertinent studies was conducted.

Results:

Nine studies were included. No consistent differences were observed in the categories of core ASDs behaviors, cognitive function, or language. The studies suggest a potential bilingual advantage on nonverbal intelligence quotient scores, adaptive functioning, and expressive vocabulary.

Conclusion:

There is no evidence of a detrimental effect of raising children with ASDs in a bilingual home.
Long-term Concentrations of Nitrogen Dioxide and Mortality
Authors: Atkinson Richard. W. , Butland Barbara. K. , Anderson H. Ross. , Maynard Robert. L.
Published: May 2018

Background:

Concentrations of outdoor nitrogen dioxide (NO2) have been associated with increased mortality. Hazard ratios (HRs) from cohort studies are used to assess population health impact and burden. We undertook meta-analyses to derive concentration–response functions suitable for such evaluations and assessed their sensitivity to study selection based upon cohort characteristics.

Methods:

We searched online databases and existing reviews for cohort studies published to October 2016 that reported HRs for NO2 and mortality. We calculated meta-analytic summary estimates using fixed/random-effects models.

Results:

We identified 48 articles analyzing 28 cohorts. Meta-analysis of HRs found positive associations between NO2 and all cause (1.02 [95% confidence interval (CI): 1.01, 1.03]; prediction interval [PI]: [0.99, 1.06] per 10 µg/m3 increment in NO2), cardiovascular (1.03 [95% CI: 1.02, 1.05]; PI: [0.98, 1.08]), respiratory (1.03 [95% CI: 1.01, 1.05]; PI: [0.97, 1.10]), and lung cancer mortality (1.05 [95% CI: 1.02, 1.08]; PI: [0.94, 1.17]) with evidence of substantial heterogeneity between studies. In subgroup analysis, summary HRs varied by age at cohort entry, spatial resolution of pollution estimates, and adjustment for smoking and body mass index at the individual level; for some subgroups, the HR was close to unity, with lower confidence limits below 1.

Conclusions:

Given the many uncertainties inherent in the assessment of this evidence base and the sensitivity of health impact calculations to small changes in the magnitude of the HRs, calculation of the impact on health of policies to reduce long-term exposure to NO2 should use prediction intervals and report ranges of impact rather than focusing upon point estimates.
Contrasting Causal Effects of Workplace Interventions
Authors: Izano Monika A. , Brown Daniel M. , Neophytou Andreas M. , Garcia Erika , Eisen Ellen A.
Published: May 2018

Occupational exposure guidelines are ideally based on estimated effects of static interventions that assign constant exposure over a working lifetime. Static effects are difficult to estimate when follow-up extends beyond employment because their identifiability requires additional assumptions. Effects of dynamic interventions that assign exposure while at work, allowing subjects to leave and become unexposed thereafter, are more easily identifiable but result in different estimates. Given the practical implications of exposure limits, we explored the drivers of the differences between static and dynamic interventions in a simulation study where workers could terminate employment because of an intermediate adverse health event that functions as a time-varying confounder. The two effect estimates became more similar with increasing strength of the health event and outcome relationship and with increasing time between health event and employment termination. Estimates were most dissimilar when the intermediate health event occurred early in employment, providing an effective screening mechanism.
Interindividual and Intraindividual Variation of Methylphenidate Concentrations in Serum and Saliva of Patients With Attention-Deficit/Hyperactivity Disorder
Authors: Preiskorn Joshua , Studer Sophie , Rauh Reinhold , Lukačin Richard , Geffert Christoph , Fleischhaker Christian , Clement Hans-Willi , Schulz Eberhard , Biscaldi Monica
Published: May 2018

Background:

Therapeutic drug monitoring is becoming increasingly important in psychiatric therapy, especially in children. However, for several reasons, it cannot yet be implemented as a daily routine in clinical or outpatient settings. To evaluate new, noninvasive procedures, blood and saliva (oral fluid) samples were collected from patients with attention-deficit/hyperactivity disorder (ADHD) who were also being administered methylphenidate (MPH). The study's main purposes were to correlate MPH concentrations in serum and saliva between subjects and to analyze intraindividual variation of serum concentration.

Methods:

Thirty-six patients with ADHD (27 children and 9 adults) on MPH medication were included for drug analysis. MPH and its major metabolite ritalinic acid were quantified using liquid chromatography–tandem mass spectrometry measurements. The following correlations were investigated: (1) between drug concentrations in serum and saliva, and (2) between pH value and saliva to serum concentration ratio. Furthermore, the mean intraindividual MPH-concentration fluctuation in saliva under constant frame conditions was analyzed.

Results:

After quantification, MPH concentrations were approximately 5 times higher in the saliva than in the serum, whereas the concentrations of ritalinic acid were much lower in saliva. We found significant correlations between concentrations of MPH in serum and saliva (r = 0.51,P< 0.05). Saliva MPH measures, compared with serum, were pH-dependent (r = −0.56,P< 0.01). Daily coefficient of variance of saliva concentration in children taking constant medication was 27.3% (11%–42%), whereas the coefficient of variance for the ratio of saliva to serum was 122% (2%–2060%).

Conclusions:

Our data indicate that the interindividual variation in saliva to serum concentrations is rather high, whereas the intraindividual variation is fairly low, as already shown in the literature for repeated citalopram serum measurements. Saliva may well serve as an alternative matrix for therapeutic drug monitoring of MPH in patients with ADHD, especially for follow-up examinations. Future research should focus on analyzing the relationship between drug levels in saliva and clinical effects as well as on understanding the mechanisms that generate saliva drug concentrations. These are essential steps before potential clinical use.
Development of an Abbreviated Mycophenolic Acid Area Under the Time–Concentration Curve for Renal Transplant Patients Under Enteric-Coated Mycophenolate Sodium: A Comparison With Critical Analysis of Available Equations
Authors: David-Neto Elias , Triboni Ana Heloisa , Ramos Fernanda , Agena Fabiana , Romano Paschoalina
Published: May 2018

Background:

Enteric-coated mycophenolate sodium is frequently used in renal transplantation. The pharmacokinetic profile of mycophenolic acid (MPA) shows a broad range of time-to-maximum concentration (Tmax) that limits the use of a single MPA concentration to calculate the area under the time–concentration curve (AUC). For both research and clinical MPA monitoring, measuring a complete AUC is troublesome to the center and patients.

Methods:

We obtained 171 complete MPA-AUC12h (0, 20, 40, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes) from 59 adult (54 ± 16 years) patients (29 men and 43 whites) who have been receiving stable doses of tacrolimus/enteric-coated mycophenolate sodium and steroids. We used the 59 curves drawn at 31 ± 4 days after transplantation to develop the abbreviated equations, and the remaining 112 curves drawn at 109 ± 59 days were used to validate them. We used 5 other proposed equations to estimate MPA-AUC (eAUC) (4 with enzyme-multiplied immunoassay technique assay and one with high-performance liquid chromatography [HPLC]) and then used these results to compare with our measured AUC, the bias, and the 10% and 30% accuracy. MPA was measured by ultraperformance liquid chromatography coupled to a tandem mass spectrometry, and AUC was calculated by the trapezoidal rule.

Results:

For both MPA-measuring methods, enzyme-multiplied immunoassay technique and ultraperformance liquid chromatography coupled to a tandem mass spectrometry, the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) equations, and others that measure MPA up to 6 hours after the dose had an acceptable low bias with more results in the 10%–30% range than those using data collected until 4 hours. A highly adequate eAUC is obtained using blood collected at 8 hours.

Conclusions:

This analysis offers blood-sampling alternatives for MPA monitoring depending on the precision needed.
Barriers and facilitators to intraorganizational collaboration in public health: Relational coordination across public health services targeting individuals and populations
Authors: McCullough J. Mac , Eisen-Cohen Eileen , Lott Breanne
Published: May 2018

Background:

Modern public health emphasizes population-focused services, which may require collaborative work both across and within organizations. Studies have explored interorganizational collaborations, but there are little data regarding collaborations within public health organizations.

Purpose:

We measured intraorganizational collaboration and identified barriers and facilitators to collaboration within a large public health department through a mixed-methods study.

Methodology/Approach:

Our study occurred at the Maricopa County (Arizona) Department of Public Health, the third largest local public health jurisdiction in the United States. To measure collaboration, we surveyed staff using the relational coordination tool. To identify barriers and facilitators to collaboration, we performed key informant interviews with department personnel.

Results:

Relational coordination scores varied according to the focus of the service; clinical services had significantly lower levels of relational coordination than population-focused services (p < .01). We found high levels of mutual respect and lower levels of shared knowledge across services. Facilitators to collaboration included purposive cross-program meetings around specific topics, the organization’s structure and culture, and individuals’ social identities. Barriers included raised expectations for collaboration, low slack resources, member’s self-interest, and trust.

Conclusion:

The relational coordination of services varied significantly according to the focus of the service. Population-focused public health services had higher levels of relational coordination than individually focused services. Collaboration was facilitated and impeded by both well-known and potentially emergent factors, such as purposive cross-service meetings and organizational culture.

Practice Implications:

Population-focused services possessed higher levels of collaboration than individually focused services. Intraorganizational collaboration for improved population health relies on deliberate support from senior management and structured activities to increase shared knowledge and mutual respect.
Descemet Membrane Endothelial Keratoplasty After Penetrating Keratoplasty: Features for Success
Authors: Einan-Lifshitz Adi , Belkin Avner , Sorkin Nir , Mednick Zale , Boutin Tanguy , Gill Ishrat , Karimi Mohammad , Chan Clara C. , Rootman David S.
Published: May 2018

Purpose:

To evaluate Descemet membrane endothelial keratoplasty (DMEK) in the setting of failed penetrating keratoplasty (PKP) and to identify factors associated with DMEK success and failure after PKP.

Methods:

A retrospective chart review of patients who underwent DMEK for failed PKP at Toronto Western Hospital, Canada, between 2014 and 2017 was performed. Demographic characteristics, number of previous transplants, intraoperative and postoperative complications, best spectacle-corrected visual acuity (BSCVA), and endothelial cell density were analyzed.

Results:

Twenty-eight eyes were included in the study. Rebubbling intervention was performed in 12 eyes (43%) within the first postoperative weeks. Five eyes (18%) developed graft rejection episodes. Twelve eyes (43%) had to be regrafted after DMEK surgery and were deemed failures (because of persistent Descemet membrane detachment, rejection episode that led to secondary failure, and infection). BSCVA before DMEK was significantly worse in the eyes that failed than those that did not [1.97 ± 0.85 and 1.2 ± 0.56 logMAR, respectively, (P = 0.01)]. Rebubbling was required in 75% of eyes in the failure group compared with 19% in the success group (P = 0.002). Six of the 16 eyes (37.5%) in the success group underwent femtosecond laser-enabled DMEK, whereas this technique was not used in any of the eyes in the failure group (P = 0.017).

Conclusions:

DMEK is a viable option for cases of failed PKP. DMEK failure after PKP might be associated with lower visual acuity before DMEK surgery, higher number of rebubble interventions, and manual descemetorhexis rather than femtosecond laser-enabled DMEK.
Corneal Cross-Linking in Pediatric Patients: Evaluating Treated and Untreated Eyes—5-Year Follow-Up Results
Authors: Or Lior , Rozenberg Assaf , Abulafia Adi , Avni Isaac , Zadok David
Published: May 2018

Purpose:

To evaluate the long-term results of corneal collagen cross-linking (CXL) for treatment of pediatric keratoconus and the long-term outcomes of the fellow untreated keratoconic eye in patients younger than 18 years old.

Methods:

A retrospective case analysis was performed on 88 eyes of 44 patients aged 18 years or younger, with keratoconus, who underwent CXL in at least 1 eye. Follow-up measurements, for the treated and untreated eye pair, taken up to 5 years after treatment, were compared with baseline values. Parameters included uncorrected distance visual acuity (UCDVA), best spectacle-corrected distance visual acuity (BCDVA), manifest refraction, pachymetry, and corneal topography and tomography.

Results:

Mean age of patients was 15.6 ± 2.1 years. For the treated eyes, during all years of follow-up, UCDVA improved significantly (from 0.83 ± 0.30 to 0.72 ± 0.28 logMAR; P = 0.01). Improvement in BCDVA was not statistically significant (from 0.28 ± 0.19 to 0.23 ± 0.15 logMAR; P = 0.06). The manifest cylinder showed a significant reduction (from 5.8 ± 3.6 to 4.3 ± 2.5 diopters; P = 0.006). There was no significant change in maximum keratometry. Average keratometry and corneal thickness reduced significantly (P = 0.009 and P = 0.002, respectively). Five patients had very mild corneal haze after CXL. For the fellow untreated eyes—during 5 years of follow-up, UCDVA showed a slight decrease that was not statistically significant. BCDVA, average keratometry, and maximum keratometry remained stable.

Conclusions:

Our long-term follow-up study suggests that CXL is a safe procedure in the pediatric age, and there is no urgency in treating pediatric patients with keratoconus without proof of progression.
Valsalva Maneuver and Peripapillary OCT Angiography Vessel Density
Authors: Holló Gábor
Published: May 2018

Purpose:

To investigate the potential influence of breath holding on the results of peripapillary vessel density (VD) measurement with optical coherence tomography angiography.

Materials and Methods:

Three peripapillary VD measurements were made at 2-minute intervals on the right eye of 12 healthy young volunteers using the Angiovue/RTvue-XR OCT (software version 2017.1, Phase 7 update) without changing the head and body positions. During the first 2 measurements the volunteers were breathing normally. Four seconds before the third measurement the participants started to perform the Valsalva maneuver and continued until the completion of the ∼17-second image acquisition. The whole image area, the inside-disc area and the peripapillary area were investigated for capillary VD and all-vessels VD, separately.

Results:

All volunteers had normal blood pressure and intraocular pressure, and all study eyes were normal with healthy optic nerve head and peripapillary area. No difference for any VD parameter was seen between the baseline images (P≥0.492). The differences between the averaged baseline and the during Valsalva maneuver values did not differ from 0 (P≥0.474), and the mean differences were ≤0.19% for the whole image, ≤0.35% for the peripapillary area, and ≤0.68% for the inside-disc parameters. The mean image quality score was >8 (optimal) in all image sessions.

Conclusions:

Our results suggest that breath holding during optical coherence tomography angiography image acquisition does not influence the measured peripapillary, whole image and inside-disc VD values, or the quality of the images, in healthy young subjects. Thus, no specific patient instruction regarding breathing is required before image acquisition.
Prevalence and Molecular Characterization of Staphylococcus aureus and Methicillin-resistant S. aureus on Children’s Playgrounds
Authors: Thapaliya Dipendra , Kadariya Jhalka , Capuano Mike , Rush Haleigh , Yee Clair , Oet Mark , Lohani Sapana , Smith Tara C.
Published: May 2018

Background:

Staphylococcus aureus is a major public health concern due to the emergence of virulent and drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA). Although numerous studies have been conducted to assess the environmental contamination of S. aureus in health care and household settings, little is known about the prevalence and epidemiology of S. aureus, including MRSA, on environmental surfaces of children’s playgrounds. This study investigated the prevalence and molecular epidemiology of S. aureus and MRSA at playgrounds in northeast Ohio.

Methods:

A total of 280 environmental samples were collected from 10 playgrounds in northeast Ohio in July 2016. Sampling sites were selected based on playground size and availability of equipment located in both small and large cities and their suburbs. Samples were analyzed using established microbiology methods, and resulting S. aureus isolates were typed by spa typing. Polymerase chain reaction was used to detect the presence of the Panton-Valentine leukocidin and mec A genes. Antibiotic susceptibility was tested via the Vitek-2 System.

Results:

The overall prevalence of S. aureus and MRSA was 31.8% (89/280) and 3.9% (11/280), respectively. A total of 43 spa types were detected from 257 S. aureus isolates. Overall, t189 was the most common spa type, accounting for 15.6% (40/257) of the isolates. Sixteen isolates (6.2%) were t002 (ST5/USA100), a common hospital-associated strain, and 11 isolates (4.3%) were t008 (ST8/USA300), a common community-associated strain. Five livestock-associated strain (t571/ST398) were also identified. Twenty-nine (11.3%) isolates were resistant to oxacillin, and 66 (25.7%) were multi-drug resistant S. aureus.

Conclusions:

The results of this study indicate that environmental surfaces of playgrounds in northeastern Ohio were contaminated with S. aureus and MRSA. These data reinforce the need for implementing effective prevention strategies to mitigate the risk imposed to children by environmental contamination of MRSA.
Risk Factors for Severe Community-aquired Pneumonia Among Children Hospitalized With CAP Younger Than 5 Years of Age
Authors: Shan Wei , Shi Ting , Chen Kaile , Xue Jian , Wang Yin , Yu Jia , Zhao Genming , Tian Jianmei , Zhang Tao
Published: May 2018

Background:

Community-acquired pneumonia (CAP) causes great morbidity and mortality as well as enormous economic burden worldwide. This study intended to describe the clinical characteristics of CAP and explore the risk factors of severe CAP among children in downtown Suzhou, China.

Methods:

This was a retrospective study of childhood hospitalizations in Soochow University Affiliated Children’s Hospital from January 1, 2010, to December 31, 2014. Children who were residents of downtown Suzhou, 29 days to < 5 years of age, with discharge diagnosis codes J09 to J18 and J20 to J22 were included. Medical charts and chest radiograph reports were reviewed for included children to collect clinical information. CAP with intensive care unit (ICU) admission and poor clinical outcome were categorized as severe CAP.

Results:

A total of 28,043 children were identified with CAP; 17,501 (62.4%) of these children were male, and 20,747 (74.0%) children were less than 2 years of age. The common clinical symptoms at admission were cough (94.8%), fever (52.9%), wheezing (37.7%) and respiratory distress (9.5%). In total, 21,898 (78.1%) children had radiologic evidence of pneumonia, and 1,403 (5.0%) children developed at least 1 complication. Multivariate regression analysis showed that younger age, congenital heart disease and abnormal white blood cells, and C-reactive protein results were independent risk factors for both ICU admission and poor clinical outcome (odds ratio [OR] > 1 for all). Respiratory distress symptoms at admission (OR = 12.10) greatly increased the risk for ICU admission, while ICU admission (OR = 8.87) and complications (OR = 2.55) increased the risk of poor outcome. However, cough was a protective factor for ICU admission, so were wheezing, antibiotic and antiviral therapies for clinical failure.

Conclusion:

Pediatric CAP hospitalizations of those of younger age, with congenital heart diseases, respiratory distress symptoms/tachypnea, abnormal white blood cells and C-reactive protein results as well as complications were at higher risk for progressing to severe CAP.
Dynamics of Severe and Non-severe Invasive Pneumococcal Disease in Young Children in Israel Following PCV7/PCV13 Introduction
Authors: Glikman Daniel , Dagan Ron , Barkai Galia , Averbuch Diana , Guri Alex , Givon-Lavi Noga , Ben-Shimol Shalom
Published: May 2018

Background:

The introduction of the pneumococcal conjugated vaccines (PCVs) resulted in a substantial reduction of invasive pneumococcal disease (IPD) rates. However, impact on nonsevere IPD (mostly occult bacteremia) has not yet been fully elucidated. We assessed severe and nonsevere IPD (SIPD and NSIPD, respectively) rate dynamics in children < 5 years in Israel before and after PCV7/PCV13 implementation.

Methods:

A prospective, population-based, nationwide surveillance. All IPD episodes recorded from 1999 through 2015 were included. NSIPD was defined as IPD episodes without meningitis, pneumonia or mastoiditis in a child with a favorable outcome (not hospitalized or hospitalized in a nonintensive care unit < 5 days, without mortality). Three subperiods were defined: pre-PCV (1999–2008), PCV7 (2010–2011) and PCV13 (2013–2015). Incidence rate ratios (IRRs) were calculated.

Results:

Overall, 4,457 IPD episodes were identified; 3,398 (76.2%) SIPD, 1,022 (22.9%) NSIPD and 37 (0.8%) unknown. In 90% of NSIPD episodes, no focus was identified. In the PCV7 period, NSIPD rates significantly declined by 52%, while SIPD rates declined less prominently by 24%. Following PCV13 introduction, compared with the PCV7 period, NSIPD rates declined nonsignificantly by 17% while SIPD rates declined significantly further by an additional 53%. These trends resulted in overall reductions (comparing PCV13 and pre-PCV periods) of NSIPD and SIPD of 60% (IRR = 0.4; 0.32–0.51) and 64% (IRR = 0.36; 0.32–0.42), respectively.

Conclusions:

Following PCV7/PCV13 introduction, SIPD and NSIPD rates substantially declined, with differences in rate-dynamics, alluding to differences in serotype distribution between the 2 groups. Future surveillance is warranted when considering modification in treatment protocols for suspected occult bacteremia/NSIPD cases.
One-year Incidence of Infection in Pediatric Intestine Transplantation
Authors: Clouse Jared W. , Kubal Chandrashekhar A. , Fridell Jonathan A. , Mangus Richard S.
Published: May 2018

Background:

This study reports the infection rate, location of infection and pathogen causing bacterial, fungal or viral infections in intestine transplant recipients at a pediatric transplant center.

Methods:

Records from a pediatric center were reviewed for patients receiving an intestine transplant. Positive cultures and pathology reports were used to diagnose bacterial, fungal and viral infections and also to determine location and infectious agent. Risk for infection was assessed based on liver or colon inclusion, and immunosuppression induction, as part of the intestine transplant.

Results:

During the study period, 52 intestine transplants were performed on 46 patients. Bacterial, fungal and viral infection rates were 90%, 25% and 75%, respectively.Enterococcusspp. (non–vancomycin-resistant enterococci) were the most common pathogens and were isolated from 52% of patients. Non–vancomycin-resistant enterococci was present in 12% of transplant recipients.Candidaspp. were the most common fungal pathogens (23% of patients). Respiratory viral infections were common (44%), andCytomegalovirusinfection rate was 17%. Common sites of infection were bloodstream, urinary and upper respiratory tract. Colon and liver inclusion in the transplant graft was not associated with increased risk of infection, nor was addition of rituximab to the immunosuppression induction protocol.

Conclusions:

Postintestine transplant infections are ubiquitous in the pediatric population, including high rates of infection from bacterial, viral and fungal sources. Inclusion of the liver and/or colon as a component of the transplant graft did not appear to greatly impact the infectious risk. Adding rituximab to the immunosuppression induction protocol did not impact on infectious risk.
Potential for More Rational Use of Antibiotics in Hospitalized Children in a Country With Low Resistance
Authors: Thaulow Christian Magnus , Berild Dag , Eriksen Beate Horsberg , Myklebust Tor Åge , Blix Hege Salvesen
Published: May 2018

Background:

Antimicrobial resistance is low in Norway, but to prevent an increase, the Norwegian Government has launched a National Strategy including a 30% reduction of broad-spectrum antibiotics (BSA) in hospitals within 2020. BSA are defined as second- and third-generation cephalosporins, carbapenems, piperacillin/tazobactam and quinolones. There are no recent studies of antibiotic use in Norwegian hospitalized children. The aim of this study was to describe the use of antibiotics with emphasis on BSA in Norwegian hospitalized children and neonates to detect possibilities for optimization.

Methods:

Data were extracted from 8 national point prevalence surveys of systemic antibiotic prescriptions in Norwegian hospitals between 2015 and 2017. The choices of antibiotics were compared with the empirical recommendations given in available Norwegian guidelines. In total, 1323 prescriptions were issued for 937 patients.

Results:

Twenty-four percent of pediatric inpatients were given antibiotics. Adherence to guidelines was 48%, and 30% (95% confidence interval: 27%–33%) of all patients on antibiotics received BSA. We identified only small variations in use of BSA between hospitals. One-third of the patients on antibiotic therapy received prophylaxis whereof 13% were given BSA. In 30% of prescriptions with BSA, no microbiologic sample was obtained before treatment.

Conclusions:

This study reveals an excess of prescriptions with BSA in relation to the low resistance rate in Norway. Our findings reveal areas for improvement that can be useful in the forthcoming antibiotic stewardship programs in Norwegian pediatric departments.
Evaluating a Nurse-Driven Mobility Algorithm for Hospitalized General Medicine Patients: A Pilot Study
Authors: Houlihan Sara , Fernandez Natalia , Magnant Christine , Levin Alyssa , Murphy Susan
Published: May 2018

Purpose:

Mobility of hospitalized patients declines substantially after transfer from an intensive care unit focused on “early mobility” to a general medicine floor. Barriers to appropriately mobilize patients are nursing staff's confidence and the perceived risks related to mobility. This study examined the effect of a nurse-driven mobility algorithm on nurse ability to identify level of functional mobility. Participants were 24 general medicine patients and 2 pairs of physical therapist (PTs) and registered nurse (RN) raters.

Methods:

Each PT/RN pair was asked to classify level of mobility for each patient using predefined tiers. RNs were given an algorithm as a guide, and PTs assessed the patient's mobility without any guidelines for predefined tiers. Comparison of the tiered level from each rater was analyzed using κ statistics.

Results:

A sample of convince consisted of 24 general medicine patients. Fair to moderate agreement was found among both sets of raters (κ= 0.40).

Conclusion:

Although the algorithm did not result in high agreement between PTs and RNs, discrepancies were largely in the tiering regarding whether the patient needed supervision versus being independent. The mobility-driven algorithm may be useful to assist nursing staff in determining the appropriate level of mobility for general medicine patients with further refinement.
Evaluating Mortality Risk Adjustment Among Children Receiving Extracorporeal Support for Respiratory Failure
Authors: Barbaro Ryan P. , Boonstra Philip S. , Kuo Kevin W. , Selewski David T. , Bailly David K. , Stone Cheryl L. , Chow Chin Ying , Annich Gail M. , Moler Frank W. , Paden Matthew L.
Published: May 2018

This study evaluates whether three commonly used pediatric intensive care unit (PICU) severity of illness scores, pediatric risk of mortality score (PRISM) III, pediatric index of mortality (PIM) 2, and pediatric logistic organ dysfunction (PELOD), are the appropriate tools to discriminate mortality risk in children receiving extracorporeal membrane oxygenation (ECMO) support for respiratory failure. This study also evaluates the ability of the Pediatric Risk Estimate Score for Children Using Extracorporeal Respiratory Support (Ped-RESCUERS) to discriminate mortality risk in the same population, and whether Ped-RESCUERS’ discrimination of mortality is improved by additional clinical and laboratory measures of renal, hepatic, neurologic, and hematologic dysfunction. A multi-institutional retrospective cohort study was conducted on children aged 29 days to 17 years with respiratory failure requiring respiratory ECMO support. Discrimination of mortality was evaluated with the area under the receiver operating curve (AUC); model calibration was measured by the Hosmer–Lemeshow goodness of fit test and Brier score. Admission PRISM-III, PIM-2, and PELOD were found to have poor ability to discriminate mortality with an AUC of 0.56 [0.46–0.66], 0.53 [0.43–0.62], and 0.57 [0.47–0.67], respectively. Alternatively, Ped-RESCUERS performed better with an AUC of 0.68 [0.59–0.77]. Higher alanine aminotransferase, ratio of the arterial partial pressure of oxygen the fraction of inspired oxygen, and lactic acidosis were independently associated with mortality and, when added to Ped-RESCUERS, resulted in an AUC of 0.75 [0.66–0.82]. Admission PRISM-III, PIM-2, and PELOD should not be used for pre-ECMO risk adjustment because they do not discriminate death. Extracorporeal membrane oxygenation population-derived scores should be used to risk adjust ECMO populations as opposed to general PICU population-derived scores.
Ranolazine for Symptomatic Management of Microvascular Angina
Authors: Rayner-Hartley Erin , Parvand Mahraz , Humphries Karin H. , Starovoytov Andrew , Park Julie E. , Sedlak Tara
Published: May 2018

Background:

Ranolazine is approved in the United States and Europe for chronic stable angina. Microvascular angina (MVA) is defined as angina with no obstructive coronary artery disease.

Study Question:

Our objective was to assess the effectiveness of ranolazine at improving angina scores and quality of life in a Canadian cohort with severe refractory angina due to MVA.

Study Design:

We administered questionnaires to 31 patients at baseline and after at least 6 weeks of ranolazine treatment.

Measures and Outcomes:

Validated, clinically significant changes for each Seattle Angina Questionnaire domain and the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form were obtained from the literature. Score changes between baseline and postranolazine use were analyzed using sign test.

Results:

Patients were mostly female (27 of 31 patients) with a median age of 57 years. After initiation of ranolazine treatment, patients experienced improvements in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form scores (80.6%; P < 0.01) and in 3 of the 4 domains of the Seattle Angina Questionnaire (physical limitation: 73.3%; P = 0.02; treatment satisfaction: 80.6%; P < 0.01; and disease perception: 77.4%; P < 0.01). Patients were less likely to have interactions with the health care system after ranolazine treatment as compared with before (35.5% vs. 93.5%; P < 0.01).

Conclusions:

Ranolazine significantly improves symptom control and quality of life in patients with MVA and severe refractory angina and reduces their interaction with the health care system. Given the potentially debilitating effect of chronic angina in MVA, ranolazine may be an effective treatment option.
Microenvironment signaling driving lymphomagenesis
Authors: Verdière Léa , Mourcin Frédéric , Tarte Karin
Published: May 2018

Purpose of review

In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, drug resistance, and late progression/transformation. The purpose of this review is to outline the most recent findings regarding malignant B-cell niche composition and organization supporting direct and indirect tumor-promoting functions of lymphoma microenvironment.

Recent findings

Lymphoma supportive niche integrates a dynamic and orchestrated network of immune and stromal cell subsets producing, with a high level of spatial and kinetic heterogeneity, extracellular and membrane factors regulating tumor migration, survival, proliferation, immune escape, as well as tumor microarchitecture, and mechanical constraints. Some recent insights have improved our understanding of these various components of lymphoma microenvironment, taking into account the mechanisms underlying the coevolution of malignant and nonmalignant cells within the tumor niche.

Deciphering tumor niche characteristics, functions, and origin could offer new therapeutic opportunities through the targeting of pivotal cellular and molecular components of the supportive microenvironment, favoring immune cell reactivation and infiltration, and/or limiting tumor retention within this protective niche.
Acquired low cholesterol: diagnosis and relevance to safety of low LDL therapeutic targets
Authors: Soran Handrean , Ho Jan Hoong , Durrington Paul N.
Published: May 2018

Purpose of review

Acquired hypocholesterolaemia occurs more commonly than inherited hypocholesterolaemia but has received little attention in the literature. In this review, we discuss the causes and underlying mechanisms of acquired hypocholesterolaemia and its relevance to safety of therapeutically induced decreased LDL cholesterol levels.

Recent findings

Hypocholesterolaemia is increasingly identified as cholesterol testing becomes more widespread in the assessment of cardiovascular risk. Lower therapeutic targets for LDL cholesterol are also being achieved more regularly with the introduction of more intensive cholesterol-lowering regimens. Acquired hypocholesterolaemia may be the presenting feature of treatable diseases. Understanding its mechanisms may also provide new treatment approaches for neoplastic disease, such as breast cancer, and infections, such as tuberculosis.

When hypocholesterolaemia is discovered, it is important to identify its cause. Further research into the pathogenesis of hypocholesterolaemia may provide new therapies for primary diseases underlying it.
Blepharoptosis repair
Authors: Liu Catherine Y. , Chhadva Priyanka , Setabutr Pete
Published: May 2018

Purpose of review

To review recent advances on the mechanisms and management of acquired aponeurotic blepharoptosis.

Recent findings

Recent advances over the past year have focused on refining well known methods of ptosis repair, expanding and modifying techniques to treat difficult and more severe conditions, and uncovering the biomechanical and neurostimulatory mechanisms of ptosis and its repair.

Innovations in ptosis repair are discussed in the context of current treatment paradigms.
Antibiotic use in facial plastic surgery
Authors: Shokri Tom , Lighthall Jessyka G.
Published: May 2018

Purpose of review

The aim of this study was to review and discuss recent literature regarding perioperative use of antibiotics in the context of facial plastic surgery.

Recent findings

Despite research efforts, there continues to be insufficient evidence in support of, or against, the use of antimicrobial prophylaxis.

Current available evidence regarding antibiotic use in facial plastic surgery procedures fails to demonstrate routine benefit. Therefore, the advantages accompanying administration of preoperative antibiotics should be weighed against any potential complications on a case-by-case basis. Future large-scale prospective studies will be beneficial in developing standardized criteria directing appropriate antibiotic use.
Management of obstructive sleep apnoea: an update on the role of distraction osteogenesis
Authors: Leung Yiu Yan , Lai Karen Kar Yan
Published: May 2018

Purpose of review

This article reviews the current literature on the use of distraction osteogenesis as a treatment for patients with obstructive sleep apnoea (OSA). We reviewed the indications, surgical protocols and outcomes for distraction osteogenesis in paediatric and adult OSA cases described in the literature.

Recent findings

There is evidence that distraction osteogenesis is effective in treating children with OSA as a result of underdevelopment of jaws such as those with craniofacial syndromes. Distraction osteogenesis appears to be the only available treatment that prevents tracheostomy in some of these cases, or allows decannulation after distraction. For adult OSA patients, distraction osteogenesis is reported to be reserved for challenging cases such as OSA as a consequence of temporomandibular joint ankylosis. It is used where conventional orthognathic surgery is not feasible. The studies reported high success rate/cure rate of OSA after distraction osteogenesis. Technological advances such as three-dimensional printing assist the execution of an accurate distraction process.

Distraction osteogenesis appears to be an effective treatment for paediatric OSA patients with craniofacial anomalies, and is used in selected cases of adult with severe OSA. With the improvement in distraction device designs and computer technology, distraction osteogenesis may play a bigger role in the treatment of OSA.
Colourism: a global adolescent health concern
Authors: Craddock Nadia , Dlova Ncoza , Diedrichs Phillippa C.
Published: May 2018

Purpose of review

Colourism, a form of prejudice and discrimination based solely upon skin colour, stands to jeopardize the physical health, wellbeing and life chances of adolescents of colour, globally.

Recent findings

Research shows that adolescents can experience colourism at school and college, in the criminal justice system, at work and in the media they consume. It is therefore unsurprising that adolescents of colour often express a desire for lighter skin tones and/or are dissatisfied with their skin tone. Although research is scarce, some studies include older adolescents in their samples of skin-lightening product users. This is significant as the evidence is clear that the unmonitored use of skin-lightening products can be harmful to physical and psychological health, with evidence linking skin-lightening use to skin damage, kidney failure and depression.

Although it is evident that colourism is central to the lives of adolescents of colour, more research is needed concerning the use of skin-lightening products among adolescents. Media literacy and critical race theory offer avenues in helping attenuate the harmful impact of colourism for adolescents of colour.
Prolonged QRS Widening After Aripiprazole Overdose
Authors: Mazer-Amirshahi Maryann , Porter Robert , Dewey Kayla
Published: May 2018

Background

Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation.

Methods

This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening.

Case

A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer.

Conclusions

This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.