bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost of treatment of peripheral neuropathic pain with pregabalin or gabapentin in routine clinical practice: impact of their loss of exclusivity
Authors: Sicras‐Mainar Antoni , Rejas‐Gutiérrez Javier , Pérez‐Páramo María , Navarro‐Artieda Ruth
Published: September 2016

To analyze the effect of loss of exclusivity of data on the cost of treatment of peripheral neuropathic pain (PNP) with pregabalin or gabapentin in routine clinical practice. A retrospective observational study, with electronic medical records for patients enrolled at primary care centers managed by the health care provider Badalona Serveis Assistencials, who initiated treatment of PNP with pregabalin or gabapentin. The analysis used drugs and resources prices for year 2015. The 1163 electronic medical records (pregabalin; N = 764, gabapentin; N = 399) for patients (62.2% women) with a mean (standard deviation) age of 59.2 (14.7) years were analyzed. Treatment duration was slightly shorter with pregabalin than with gabapentin (5.2 vs 5.5 months; P = 0.124), with mean doses of 227.4 (178.6) mg and 900.0 (443.4) mg, respectively. The average study drug cost per patient was higher for pregabalin than for gabapentin; €214.6 (206.3) vs €157.4 (181.9), P < 0.001, although the cost of concomitant analgesic medication was lower; €176.5 (271.8) vs €306.7 (529.2), P < 0.001. The adjusted average total cost per patient was lower in those treated with pregabalin than in those treated with gabapentin; €2,413 (2119‐2708) vs €3201 (2806–3.597); P = 0.002, owing to significantly lower health care costs; €1307 (1247‐1367) vs €1538 (1458‐1618), P < 0.001, and also non‐health care costs; €1106 (819‐1393) vs €1663 (1279‐2048), P = 0.023, that was caused by a significantly lower use of concomitant medication, fewer medical visits to primary care, and fewer days of sick leave. After loss of exclusivity of both drugs, pregabalin continued to show lower health care and non‐health care costs than gabapentin in the treatment of PNP in routine clinical practice.
Immediate Implant Placement of a Single Central Incisor Using a CAD/CAM Crown‐Root Form Technique: Provisional to Final Restoration
Authors: Vafiadis Dean , Goldstein Gary , Garber David , Lambrakos Anthony , Kowalski Bj
Published: September 2016

Objective

Preserving soft and hard tissues after extraction and implant placement is crucial for anterior esthetics. This technique will show how the information gathered from a cone‐beam computed tomography (CBCT) scan of the maxillary left central incisor and an intra‐oral digital impression can be merged to fabricate a CAD/CAM crown‐root matrix to be used as an immediate provisional restoration that mimics the natural anatomy.

Clinical Considerations

Due to trauma, a left central incisor appeared to be fractured and was scheduled for extraction and implant placement. The crown‐root configuration captured by the CBCT scan was merged with the digital files from an intra‐oral digital impression. A CAD/CAM crown‐root matrix was fabricated. Because the matrix shell was fabricated with the exact anatomy of the natural tooth, it replicated the position and three dimensional anatomy of the soft and hard tissue. It was connected to the implant with a customized provisional abutment. A digital impression of a coded healing abutment was made to fabricate the final implant abutment and final restoration. Throughout the treatment time and 36 months after completion, the thickness of tissue, emergence profile, and adjacent papilla was analyzed by clinical evaluation and photography and seemed to be maintained.

Conclusion

The use of a pre‐operative intra‐oral digital scan of the clinical crown‐root architecture and the CBCT scan of the bone/root anatomy, can be used together to fabricate a CAD/CAM crown‐root form provisional matrix. This digital design helps in the preservation of the 3D tissue topography, as well as the final restoration.

Clinical Significance

The preservation of soft and hard tissue after extraction and implant placement has always been paramount for ideal anterior implant esthetics. Using the information from digital files from CBCT scans and intra‐oral scans may help the clinician identify critical anatomical features that can be replicated in the provisional and final CAD/CAM restoration. (J Esthet Restor Dent 29:13–21, 2017)
Sensitivity and specificity of real‐time PCR and bacteriological culture for francisellosis in farm‐raised Nile tilapia (Oreochromis niloticus L.)
Authors: Assis G B N , de Oliveira T F , Gardner I A , Figueiredo H C P , Leal C A G
Published: September 2016

Despite the worldwide occurrence of Francisella noatunensis subsp. orientalis (Fno) infection in farmed tilapia, sensitivity and specificity estimates of commonly used diagnostic tests have not been reported. This study aimed to estimate the sensitivity and specificity of bacteriological culture and qPCR to detect Fno infection. We tested 559 fish, sampled from four farms with different epidemiological scenarios: (i) healthy fish in a hatchery free of Fno; (ii) targeted sampling of diseased fish with suggestive external clinical signs of francisellosis during an outbreak; (iii) convenience sampling of diseased and clinically healthy fish during an outbreak; and (iv) sampling of healthy fish in a cage farm without a history of outbreaks, but with francisellosis reported in other farms in the same reservoir. The qPCR had higher median sensitivity (range, 48.8–99.5%) than culture (range, 1.6–74.4%). Culture had a substantially lower median sensitivity (1.6%) than qPCR (48.8%) to detect Fno in carrier tilapia (farm 4). Median specificity estimates for both tests were >99.2%. The qPCR is the superior test for use in surveillance and monitoring programmes for francisellosis in farmed Nile tilapia, but both tests have high sensitivity and specificity which make them fit for use in the diagnosis of Fno outbreaks.
Investigations into the temporal development of epitheliocystis infections in brown trout: a histological study
Authors: Guevara Soto M , Vidondo B , Vaughan L , Rubin J‐F , Segner H , Samartin S , Schmidt‐Posthaus H
Published: September 2016

Epitheliocystis in Swiss brown trout (Salmo trutta) is a chlamydial infection, mainly caused by Candidatus Piscichlamydia salmonis and Candidatus Clavichlamydia salmonicola. To gain a better understanding of the temporal development of infections in wild brown trout, we investigated epitheliocystis infections during the course of the summer and autumn months of a single year (2015), and compared this to sampling points over the span of the years 2012–2014. The survey focused on tributaries (Venoge and Boiron) of the Rhone flowing in to Lake Geneva. When evaluated histologically, epitheliocystis infections were found throughout the period of investigation with the exception of the month of June. Fifty to 86 animals per sampling were investigated. Highest prevalence and infection intensities were seen in September. A correlation between epitheliocystis infection and water temperatures was not evident. Interyear comparison revealed consistent levels of prevalence and infection intensities in late summer. The absence of infections in June, combined with the consistent interyear results, indicates seasonal fluctuation of epitheliocystis infections in brown trout with a reservoir persisting during winter months from which infections can re‐initiate each year. This could either be at levels below detection limits within the brown trout population itself or in an alternative host.
Exploring Home Care Interventions for Frail Older People in Belgium: A Comparative Effectiveness Study
Authors: de Almeida Mello Johanna , Declercq Anja , Cès Sophie , Van Durme Thérèse , Van Audenhove Chantal , Macq Jean
Published: September 2016

Objectives

To examine the effects of home care interventions for frail older people in delaying permanent institutionalization during 6 months of follow‐up.

Design

Longitudinal quasi‐experimental research study, part of a larger study called Protocol 3.

Setting

Community care in Belgium.

Participants

Frail older adults who received interventions (n = 4,607) and a comparison group of older adults who did not (n = 3,633). Organizations delivering the interventions included participants provided they were aged 65 and older, frail, and at risk of institutionalization. A comparison group was established consisting of frail older adults not receiving any interventions.

Intervention

Home care interventions were identified as single component (occupational therapy (OT), psychological support, night care, day care) or multicomponent. The latter included case management (CM) in combination with OT and psychological support or physiotherapy, with rehabilitation services, or with OT alone.

Measurements

The interRAI Home Care (HC) was completed at baseline and every 6 months. Data from a national database were used to establish a comparison group. Relative risks of institutionalization and death were calculated using Poisson regression for each type of intervention.

Results

A subgroup analysis revealed that 1,999 older people had mild impairment, and 2,608 had moderate to severe impairment. Interventions providing only OT and interventions providing CM with rehabilitation services were effective in both subpopulations.

Conclusion

This research broadens the understanding of the effects of different types of community care interventions on the delay of institutionalization of frail older people. This information can help policy‐makers to plan interventions to avoid early institutionalization.
High Prevalence of Medication Discrepancies Between Home Health Referrals and Centers for Medicare and Medicaid Services Home Health Certification and Plan of Care and Their Potential to Affect Safety of Vulnerable Elderly Adults
Authors: Brody Abraham A. , Gibson Bryan , Tresner‐Kirsch David , Kramer Heidi , Thraen Iona , Coarr Matthew E. , Rupper Randall
Published: September 2016

Objectives

To describe the prevalence of discrepancies between medication lists that referring providers and home healthcare (HH) nurses create.

Design

The active medication list from the hospital at time of HH initiation was compared with the HH agency's plan of care medication list. An electronic algorithm was developed to compare the two lists for discrepancies.

Setting

Single large hospital and HH agency in the western United States.

Participants

Individuals referred for HH from the hospital in 2012 (N = 770, 96.3% male, median age 71).

Measurements

Prevalence was calculated for discrepancies, including medications missing from one list or the other and differences in dose, frequency, or route for medications contained on both lists.

Results

Participants had multiple medical problems (median 16 active problems) and were taking a median of 15 medications (range 1–93). Every participant had at least one discrepancy; 90.1% of HH lists were missing at least one medication that the referring provider had prescribed, 92.1% of HH lists contained medications not on the referring provider's list, 89.8% contained medication naming errors. 71.0% contained dosing discrepancies, and 76.3% contained frequency discrepancies.

Conclusion

Discrepancies between HH and referring provider lists are common. Future work is needed to address possible safety and care coordination implications of discrepancies in this highly complex population.
An Interim Analysis of an Advance Care Planning Intervention in the Nursing Home Setting
Authors: Hickman Susan E. , Unroe Kathleen T. , Ersek Mary T. , Buente Bryce , Nazir Arif , Sachs Greg A.
Published: September 2016

Objectives

To describe processes and preliminary outcomes from the implementation of a systematic advance care planning (ACP) intervention in the nursing home setting.

Design

Specially trained project nurses were embedded in 19 nursing homes and engaged in ACP as part of larger demonstration project to reduce potentially avoidable hospitalizations.

Setting

Nursing homes.

Participants

Residents enrolled in the demonstration project for a minimum of 30 days between August 2013 and December 2014 (n = 2,709) and residents currently enrolled in March 2015 (n = 1,591).

Measurements

ACP conversations were conducted with residents, families, and the legal representatives of incapacitated residents using a structured ACP interview guide with the goal of offering ACP to all residents. Project nurses reviewed their roster of currently enrolled residents in March 2015 to capture barriers to engaging in ACP.

Results

During the initial implementation phase, 27% (731/2,709) of residents had participated in one or more ACP conversations with a project nurse, resulting in a change in documented treatment preferences for 69% (504/731). The most common change (87%) was the generation of a Physician Orders for Scope of Treatment form. The most frequently reported barrier to ACP was lack of time.

Conclusion

The time‐ and resource‐intensive nature of robust ACP must be anticipated when systematically implementing ACP in the nursing home setting. The fact that these conversations resulted in changes over 2/3 of the time reinforces the importance of deliberate, systematic ACP to ensure that current treatment preferences are known and documented so that these preferences can be honored.
Effects of Longitudinal Glucose Exposure on Cognitive and Physical Function: Results from the Action for Health in Diabetes Movement and Memory Study
Authors: Beavers Kristen M. , Leng Iris , Rapp Stephen R. , Miller Michael E. , Houston Denise K. , Marsh Anthony P. , Hire Don G. , Baker Laura D. , Bray George A. , Blackburn George L. , Hergenroeder Andrea L. , Jakicic John M. , Johnson Karen C. , Korytkowski Mary T. , Dorsten Brent Van , Kritchevsky Stephen B. ,   the Action for Health in Diabetes Movement and Memory Ancillary Study Research Group
Published: September 2016

Objectives

To test whether average long‐term glucose exposure is associated with cognitive and physical function in middle‐aged and younger‐old adults with type 2 diabetes mellitus.

Design

Prospective cohort study.

Setting

Data obtained as part of the Action for Health in Diabetes (Look AHEAD) trial (NCT00017953) and Look AHEAD Movement and Memory ancillary study (NCT01410097).

Participants

Overweight and obese individuals with type 2 diabetes mellitus aged 45 to 76 at baseline (N = 879).

Measurements

Glycosylated hemoglobin (HbA1c) was measured at regular intervals over 7 years, and objective measures of cognitive function (Trail‐Making Test, Modified Stroop Color‐Word Test, Digit Symbol‐Coding, Rey Auditory Verbal Learning Test, Modified Mini‐Mental State Examination) and physical function (Short Physical Performance Battery, expanded Physical Performance Battery, 400‐m and 20‐m gait speed) and strength (grip and knee extensor strength) were assessed at the Year 8 or 9 follow‐up examination.

Results

Average HbA1c exposure was 7.0 ± 1.1% (53 ± 11.6 mmol/mol), with 57% of participants classified as having HbA1c levels of less than 7% (<53 mmol/mol), 27% having levels of 7% to 8% (53–64 mmol/mol), and 16% having levels of greater than 8% (>64 mmol/mol). After adjustment for age, sex, race, education, smoking status, alcohol intake, knee pain, physical fitness, body mass index, diabetes mellitus medication and statin use, ancillary year visit, and study arm and site, higher HbA1c was associated with worse physical but not cognitive function. Further adjustment for prevalent diabetes mellitus–related comorbidities made all associations nonsignificant. Results did not differ when stratified according to participant baseline age (<60 vs ≥ 60).

Conclusion

Results presented here suggest that, in the absence of diabetes mellitus–related complications, longitudinal glucose exposure is not associated with future cognitive and physical function. Optimal management of diabetes mellitus–related comorbidities may prevent or reduce the burden of disability associated with type 2 diabetes mellitus.
Nurses’ Use of Race in Clinical Decision Making
Authors: Sellers Sherrill L. , Moss Melissa E. , Calzone Kathleen , Abdallah Khadijah E. , Jenkins Jean F. , Bonham Vence L.
Published: September 2016

Purpose

To examine nurses’ self‐reported use of race in clinical evaluation.

Design

This cross‐sectional study analyzed data collected from three separate studies using the Genetics and Genomics in Nursing Practice Survey, which includes items about use of race and genomic information in nursing practice. The Racial Attributes in Clinical Evaluation (RACE) scale was used to measure explicit clinical use of race among nurses from across the United States.

Methods

Multivariate regression analysis was used to examine associations between RACE score and individual‐level characteristics and beliefs in 5,733 registered nurses.

Findings

Analysis revealed significant relationships between RACE score and nurses’ race and ethnicity, educational level, and views on the clinical importance of patient demographic characteristics. Asian nurses reported RACE scores 1.41 points higher than White nurses (p < .001), and Black nurses reported RACE scores 0.55 points higher than White nurses (p < .05). Compared to diploma‐level nurses, the baccalaureate‐level nurses reported 0.69 points higher RACE scores (p < .05), master's‐level nurses reported 1.63 points higher RACE scores (p < .001), and doctorate‐level nurses reported 1.77 points higher RACE scores (p < .01). In terms of clinical importance of patient characteristics, patient race and ethnicity corresponded to a 0.54‐point increase in RACE score (p < .001), patient genes to a 0.21‐point increase in RACE score (p < .001), patient family history to a 0.15‐point increase in RACE score (p < .01), and patient age to a 0.19‐point increase in RACE score (p < .001).

Conclusions

Higher reported use of race among minority nurses may be due, in part, to differential levels of racial self‐awareness. A relatively linear positive relationship between level of nursing degree nursing education and use of race suggests that a stronger foundation of knowledge about genetic ancestry, population genetics and the concept “race” and genetic ancestry may increase in clinical decision making could allow nurses to more appropriately use of race in clinical care. Integrating patient demographic characteristics into clinical decisions is an important component of nursing practice.

Clinical Relevance

Registered nurses provide care for diverse racial and ethnic patient populations and stand on the front line of clinical care, making them essential for reducing racial and ethnic disparities in healthcare delivery. Exploring registered nurses’ individual‐level characteristics and clinical use of race may provide a more comprehensive understanding of specific training needs and inform nursing education and practice.
Percutaneous Pulmonary Valve Implantation‐Associated Ventricular Tachycardia in Congenital Heart Disease
Authors: Loar Robert W. , Qureshi Athar M. , Miyake Christina Y. , Valdes Santiago O. , Kim Jeffrey J. , De la Uz Caridad M.
Published: September 2016

Background

Percutaneous pulmonary valve implantation (PPVI) is utilized for dysfunctional right ventricular outflow tracts (RVOT) to relieve obstruction, regurgitation, and RV dysfunction. PPVI has not been reported to induce arrhythmias. This study is the first to report the incidence of ventricular tachycardia (VT) after PPVI.

Methods

This was a retrospective study of all patients who had PPVI at a single institution. All patients were admitted after PPVI for overnight telemetry monitoring. Patients with no prior history of VT and newly detected VT within 24 hours post‐PPVI were considered to have VT related to PPVI.

Results

In total, 79 patients had PPVI (age 17 ± 9 years, 66% tetralogy of Fallot/pulmonary atresia). PPVI‐related VT was detected in 6 patients (7.5%). These patients had a lower BMI (17.5 ± 2.0 vs. 23.1 ± 6.6, P = 0.04). There was no difference in age, native conduit or percutaneous valve size, or change in the minimum diameter of the RVOT from pre‐ to post‐PPVI. In the 6 patients, VT was non‐sustained and monomorphic at rates between 120 and 170. Five started on β‐blockers. No patient required surgical explantation of the valve. Over a median follow‐up of 2 years, 4 have weaned off medications and all are free of recurrence of VT with normal Holters.

Conclusions

PPVI may be associated with transient VT in the acute peri‐procedural period. Patients of smaller size may be more susceptible. All patients were managed conservatively and none of the patients had a recurrence, which is suggestive of a transient phenomenon.
Unbalanced lateral mandibular deviation associated with TMJ sound as a sign in TMJ disc dysfunction diagnosis
Authors: Widmalm S. E. , Dong Y. , Li B. X. , Lin M. , Fan L. J. , Deng S. M.
Published: September 2016

The aim was to study the characteristics of lateral mandibular horizontal deviations during opening–closing movements and their association with TMJ sounds of the clicking type. Subjects were 28 healthy volunteers and 38 patients diagnosed with MRI imaging as having TMJ disc dysfunction, 22 with disc displacement without (DD) and 16 as having disc displacement with reduction (DDR). TMJ sounds were recorded with miniature microphones placed in the ear canals, and jaw movements were documented with a kinesiograph. A sign, unbalanced lateral deviation (ubd) was defined as a rapid, short duration, change in jaw movement direction from, and back to, a smooth deviation path in the horizontal plane. The hypotheses were that degrees of maximal deviations, proportions of unbalanced deviation (ubd) and such deviation associated with TMJ sounds (ubdS), differ between healthy subjects and patients with DD or DDR. Comparisons between groups were made using one‐way anova and chi‐square analysis, as appropriate. No differences were found between groups regarding degree of lateral deviation per se. The proportions of ubd and ubdS were significantly higher in patients with DDR than in healthy subjects and than in patients with DD (P < 0·001), but no such differences were found between healthy subjects and patients with DD. For prediction of DDR, the sensitivity and specificity of the sign ubdS were found to be 68·8% and 89·3%, respectively. For the sign ubd, they were 100·0% and 64·3%. This indicates that the sign ubdS has diagnostic value in screening for DDR.
Potential of the Cnidium monnieri fruits as an immune enhancer in Escherichia coli infection model
Authors: Malla Bindu , Chang Bo Yoon , Kim Seon Beom , Park Hyun , Lee Mi Kyeong , Kim Sung Yeon
Published: September 2016

Objectives

The Cnidium monnieri fruits (CMF) were studied how they act on immune system as a novel immunostimulator against the infectious disease.

Methods

Macrophages were treated with CMF, and nitric oxide (NO) and tumour necrosis factor-α (TNF-α) were measured, and phagocytosis of macrophages was detected using FITC-labelled Escherichia coli. The protective effect of CMF against E. coli infection in mice was examined. The survival rate was monitored daily for up to 5 days. And then the viable bacteria count of serum and the immunological mediator (NO, TNF-α, interleukin (IL)-12 and IL-6) of serum, splenocyte and peritoneal macrophages were analysed.

Key findings

The CMF significantly enhanced the concentrations of NO and TNF-α and the phagocytosis activity in macrophages. The oral administration of CMF for five consecutive days before infection prolonged the survival rate. Treatment with CMF significantly stimulated the phagocytosis of peritoneal macrophages and induced the immunological mediator of serum, splenocyte and peritoneal macrophages against the E. coli infection.

Conclusions

The host-protective effects of CMF might be archived by improving immune response, and CMF could act to prevent pathogenic microbial infections with immunomodulation.
Effect of metal-cation antacids on the pharmacokinetics of 1200 mg raltegravir
Authors: Krishna Rajesh , East Lilly , Larson Patrick , Valiathan Chandni , Butterfield Kristin , Teng Yang , Hernandez-Illas Martha
Published: September 2016

Objectives

Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice daily (BID). Raltegravir for once-daily regimen (QD) at a dose of 1200 mg is under development. The effect of calcium carbonate and magnesium/aluminium hydroxide antacids on the pharmacokinetics of a 1200 mg dose of raltegravir was assessed in this study.

Methods

An open-label, four-period, four-treatment, fixed-sequence study in 20 HIV-infected patients was performed. Patients needed to be on raltegravir as part of a stable treatment regimen for HIV, and upon entry into the trial received 5 days of 1200 mg raltegravir as pretreatment, before they entered the four-period study: 1200 mg of raltegravir alone (period 1), calcium carbonate antacid as TUMS® Ultra Strength (US) 1000 and 1200 mg raltegravir given concomitantly (Period 2), magnesium/aluminium hydroxide antacid as 20 ml MAALOX® Maximum Strength substitute MS given 12 h after administration of 1200 mg raltegravir (period 3), and calcium carbonate antacid as TUMS® US 1000 given 12 h after administration of 1200 mg raltegravir (period 4). Patients received their dose of 1200 mg QD raltegravir during the intervals between periods to re-establish steady state. AUC0–24, C24, Cmax and Tmax were calculated from the individual plasma concentrations of 1200 mg QD raltegravir after administration alone or with a calcium carbonate antacid or with a staggered dose of a calcium carbonate antacid or magnesium/aluminium hydroxide antacid. Adverse events, in addition to laboratory safety tests (haematology, serum chemistry and urinalysis), 12-lead electrocardiograms and vital signs were assessed.

Key findings

All treatments were well tolerated in the study. Metal-cation antacids variably affected the pharmacokinetics of 1200 mg QD raltegravir. When calcium carbonate antacid was given with 1200 mg raltegravir concomitantly, the geometric mean ratio (GMR) and its associated 90% confidence interval (90% CI) for AUC0–24, Cmax and C24 h were 0.28 (0.24, 0.32), 0.26 (0.21, 0.32) and 0.52 (0.45, 0.61), respectively. When calcium carbonate antacid and magnesium/aluminium hydroxide were given 12 h after raltegravir 1200 mg QD dosing, the GMR (90% CI) values for AUC0–24 and Cmax were 0.90 (0.80, 1.03), 0.98 (0.81, 1.17), and 0.86 (0.73, 1.03), 0.86 (0.65, 1.15), respectively. However, significant reduction in the trough concentrations of raltegravir was observed: C24 h 0.43 (0.36, 0.51) in the presence of calcium carbonate antacids and 0.42 (0.34, 0.52) in presence of magnesium/aluminium hydroxide, respectively.

Conclusions

Overall, the use of metal-cation antacids with 1200 mg QD raltegravir is not recommended.
Deferasirox pharmacokinetic and toxicity correlation in β-thalassaemia major treatment
Authors: Allegra Sarah , De Francia Silvia , Cusato Jessica , Pirro Elisa , Massano Davide , Piga Antonio , D'Avolio Antonio
Published: September 2016

Objectives

Deferasirox adverse effects include the following: gastrointestinal disturbance, mild elevations in serum creatinine levels and intermittent proteinuria; these events are dose-dependent and reversible with drug discontinuation, but this solution can lead to an inadequate iron chelation. For these reasons, interindividual variability of drug plasma concentration could help the clinical management of deferasirox dosage. We sought to describe deferasirox plasma exposure in a cohort of 60 adult patients.

Methods

A fully validated chromatographic method was used to quantify deferasirox concentration in plasma collected from β-thalassaemia adult patients. Samples obtained before and after 2, 4, 6 and 24 h drug administration were evaluated. Associations between variables were tested using the Pearson test.

Key findings

Concerning pharmacokinetic parameters, a higher interindividual variability was shown. A positive correlation was found between deferasirox area under the concentration curve over 24 h and serum creatinine (r = 0.314; P = 0.018) and between area and drug dose (r = 0.311; P = 0.016). Moreover, a negative correlation resulted among area under the concentration curve over 24 h and serum ferritin (r = −0.291; P = 0.026) and among drug half-life and its dose (r = −0.319; P = 0.013).

Conclusions

Treatment decision based on the individual characteristics could strongly contribute to minimize toxicity and increase efficacy of deferasirox therapy.
A preliminary study searching for the right dose of tacrolimus in very young (≤4 years) renal transplant patients
Authors: Martial Lisa C , Verstegen Ruud H J , Cornelissen Elisabeth A M , Aarnoutse Rob E , Schreuder Michiel F , Brüggemann Roger J M
Published: September 2016

Objectives

The Radboudumc Amalia Children's hospital in the Netherlands has a programme for renal transplantation in children aged ≤4 years. Children receive chronic corticosteroid sparing immunosuppressive therapy that consists of tacrolimus and mycophenolate mofetil. This work aimed to describe the PK of tacrolimus in children ≤4 years with renal transplants.

Methods

Paediatric renal transplant patients aged ≤4 years were included in this analysis. A PK curve of tacrolimus recorded ≤3 weeks after transplantation has been standard of care in our institution and aided in adjusting the dose in each patient to attain a target AUC0–12h of 210 μg h/l early after transplantation.

Key findings

Eight patients were included. The first two patients received an initial twice-daily regimen and the subsequent six patients a three-times daily regimen. Median dose-corrected AUCtau was 63 μg h/l. AUC target attainment was 37.5%. Of the remaining patients, two had an AUC very close to (around 10% below) the target.

Conclusions

Large interindividual variability of tacrolimus was observed and showed suboptimal AUC target attainment. In this population, an even more aggressive approach of higher doses (e.g. 0.4 mg/kg per day) and more early AUC determination should be considered. This should be evaluated prospectively in a larger group of patients.
Zofenopril exerts a cardiovascular protective effect on rats infused with angiotensin II beyond angiotensin-converting enzyme inhibition
Authors: Gómez-Roso Miriam , Montero María J , Carrón Rosalía , Sevilla María A
Published: September 2016

Objectives

Elevated levels of angiotensin II are implicated in the hypertensive pathophysiological process. Zofenopril has a sulphydryl group which gives it antioxidant properties. The aim of this study was to investigate its beneficial effects beyond angiotensin-converting enzyme (ACE) inhibition using angiotensin II-infused rats as hypertension model.

Methods

Zofenopril was added in drinking water. Systolic blood pressure was assessed by the tail-cuff method. Left ventricular weight/body weight ratio was calculated as cardiac hypertrophy index. An estimate of the cardiac collagen was performed by measuring the content of hydroxyproline. Vascular reactivity was evaluated on aortic rings and isolated perfused kidney, and vascular structure in thoracic aorta was studied. Superoxide anion generation was quantified in aorta by lucigenin-enhanced chemiluminescence.

Key findings

Zofenopril partially prevented the increase in systolic blood pressure and cardiac hypertrophy induced by angiotensin II and avoided the increase in collagen deposition. The treatment improved vasorelaxing responses, reversed the vascular remodelling and abolished the effects of angiotensin II on the production of O2−. It is worth to mention that all these results are observed even with high levels of plasma angiotensin.

Conclusion

Zofenopril could exert additional beneficial effects beyond ACE inhibition that would justify the improvement of pathophysiological processes triggered by angiotensin II.
Legitimacy‐Seeking Mechanisms in Product Innovation: A Qualitative Study*
Authors: Bunduchi Raluca
Published: September 2016

Product innovation research adopts a rational choice perspective to examine resource allocation decisions for product innovation. This research emphasizes strategic alignment between the innovation and the organization as the key factor shaping these decisions. In contrast, organizational research suggests that to access resources, product innovations have to be perceived as legitimate by corporate sponsors. Legitimacy is rooted in alignment with the prevalent corporate norms, beliefs, and cultural model. Adopting an institutional perspective and relying on an in‐depth case study of three product innovations, this study explores legitimacy‐seeking behavior in product innovation. The findings indicate that the rational perspective emphasized in most product innovation research is complemented by efforts to seek both moral and cognitive legitimacy to resource product innovation. The study clarifies the critical role that the organizational context plays in triggering legitimacy‐seeking behavior. The analysis unpacks legitimacy‐seeking behavior, revealing patterns of legitimating mechanisms (lobbying, relationship building, and gathering feedback) that are deployed as part of legitimacy strategies (conforming, selecting, and manipulating) to achieve a range of legitimacy outcomes (pragmatic, moral, and cognitive). The analysis reveals the existence of a hierarchy of legitimacy outcomes as actors prioritize one type of legitimacy versus another. The study also finds interdependencies between mechanisms and strategies to reinforce particular outcomes as legitimacy‐seeking behavior evolves over time.
Preliminary analysis of the concurrent validity of the Spanish translation of the BEARS sleep screening tool for children
Authors: Bastida‐Pozuelo M. F. , Sánchez‐Ortuño M. M.
Published: September 2016

Accessible summary

What is known on the subject?

Paediatric sleep problems are clinical conditions that often coexist with other mental health problems and meet criteria that warrant the implementation of screening procedures, including high prevalence, and significant clinical impact.

Researchers have designed the BEARS, a user‐friendly paediatric sleep screening tool that seems to increase the amount of sleep information recorded, as well as the likelihood of identifying sleep problems during routine health encounters. Nonetheless, there are no studies using the BEARS in Spanish‐speaking samples.

What this paper adds to existing knowledge?

Using a sample of children with mental health problems, this study provides support for the use of the Spanish version of the BEARS to identify the most common sleep problems seen in paediatric populations.

What are the implications for practice?

Considering how frequent sleep problems are, it is especially important for health professionals working with children in general, and with children with mental health problems in particular, to be aware of and be encouraged to use simple brief screening tools for paediatric sleep problems.

Objective

Research studies describe a high prevalence of sleep problems in children with mental health problems, up to 50%, and its role as a risk factor in the development of psychopathology. These often go unnoticed and are not evaluated in the clinical field. Our objective was to assess the concurrent validity of the BEARS, a brief paediatric sleep screening instrument, using the Children Sleep Habits Questionnaire (CSHQ) as the comparison instrument.

Methods

In this cross‐sectional descriptive study, the BEARS was applied by a registered nurse to a sample of parents of children aged 2–16 years (n = 60, 71.7% male) who attended a mental healthcare facility (located in Murcia, Spain) for the first time to receive a group psychoeducational intervention. The association between the information collected with the BEARS and scores on the related subscales of the CSHQ was assessed by Mann–Whitney U tests.

Results

Children who, according to the BEARS, had a sleep problem obtained scores on the CSHQ‐related subscales significantly higher than children who did not have a sleep problem (all Ps < 0.05).

Conclusion

Our results support the concurrent validity of the Spanish translation of the BEARS to detect sleep problems in paediatric nursing assessments. Further studies, with bigger and more heterogeneous samples, are warranted.
Hiding in the howardites: Unequilibrated eucrite clasts as a guide to the formation of Vesta's crust
Authors: Mayne Rhiannon G. , Smith Samantha E. , Corrigan C. M.
Published: September 2016

204 howardites in the National Meteorite Collection at the Smithsonian were examined for the presence of fine‐grained eucrite clasts, with the goal of better understanding the formation of the uppermost crust of asteroid 4Vesta. Eight clasts were identified and characterized in terms of their textures and mineral chemistry, and their degree of thermal metamorphism was assessed. The paucity of fine‐grained eucrites, both within the unbrecciated eucrites and as clasts within the howardites, suggests that they originate from small‐scale units on the surface of Vesta, most likely derived from partial melting. Six of the eight clasts described were found to be unequilibrated, meaning that they preserve their original crystallization trends. The vast majority of eucrites are at least partially equilibrated, making these samples quite rare and important for deciphering the petrogenesis of the vestan crust. Biomodal grain populations suggest that eucrite melts often began crystallizing pyroxene and plagioclase during their ascent to the surface, where they were subject to more rapid cooling, crystallization, and later metasomatism. Pyroxene compositions from this study and prior work indicate that the products of both primitive and evolved melts were present at the vestan surface after its formation. Two howardite thin sections contained multiple eucrite composition clasts with different crystallization and thermal histories; this mm‐scale diversity reflects the complexity of the current day vestan surface that has been observed by Dawn.
How old are you? Genet age estimates in a clonal animal
Authors: Devlin‐Durante M. K. , Miller M. W. ,   Caribbean Acropora Research Group, Precht W. F. , Baums I. B.
Published: September 2016

Foundation species such as redwoods, seagrasses and corals are often long‐lived and clonal. Genets may consist of hundreds of members (ramets) and originated hundreds to thousands of years ago. As climate change and other stressors exert selection pressure on species, the demography of populations changes. Yet, because size does not indicate age in clonal organisms, demographic models are missing data necessary to predict the resilience of many foundation species. Here, we correlate somatic mutations with genet age of corals and provide the first, preliminary estimates of genet age in a colonial animal. We observed somatic mutations at five microsatellite loci in rangewide samples of the endangered coral, Acropora palmata (n = 3352). Colonies harboured 342 unique mutations in 147 genets. Genet age ranged from 30 to 838 years assuming a mutation rate of 1.195−04 per locus per year based on colony growth rates and 236 to 6500 years assuming a mutation rate of 1.542−05 per locus per year based on sea level changes to habitat availability. Long‐lived A. palmata genets imply a large capacity to tolerate past environmental change, and yet recent mass mortality events in A. palmata suggest that capacity is now being frequently exceeded.
Global genetic diversity ofAedes aegypti
Authors: Gloria‐Soria Andrea , Ayala Diego , Bheecarry Ambicadutt , Calderon‐Arguedas Olger , Chadee Dave D. , Chiappero Marina , Coetzee Maureen , Elahee Khouaildi Bin , Fernandez‐Salas Ildefonso , Kamal Hany A. , Kamgang Basile , Khater Emad I. M. , Kramer Laura D. , Kramer Vicki , Lopez‐Solis Alma , Lutomiah Joel , Martins Ademir , Micieli Maria Victoria , Paupy Christophe , Ponlawat Alongkot , Rahola Nil , Rasheed Syed Basit , Richardson Joshua B. , Saleh Amag A. , Sanchez‐Casas Rosa Maria , Seixas Gonçalo , Sousa Carla A. , Tabachnick Walter J. , Troyo Adriana , Powell Jeffrey R.
Published: September 2016

Mosquitoes, especiallyAedes aegypti, are becoming important models for studying invasion biology. We characterized genetic variation at 12 microsatellite loci in 79 populations ofAe. aegyptifrom 30 countries in six continents, and used them to infer historical and modern patterns of invasion. Our results support the two subspeciesAe. aegypti formosusandAe. aegypti aegyptias genetically distinct units.Ae. aegypti aegyptipopulations outside Africa are derived from ancestral African populations and are monophyletic. The two subspecies co‐occur in both East Africa (Kenya) and West Africa (Senegal). In rural/forest settings (Rabai District of Kenya), the two subspecies remain genetically distinct, whereas in urban settings, they introgress freely. Populations outside Africa are highly genetically structured likely due to a combination of recent founder effects, discrete discontinuous habitats and low migration rates. Ancestral populations in sub‐Saharan Africa are less genetically structured, as are the populations in Asia. Introduction ofAe. aegyptito the New World coinciding with trans‐Atlantic shipping in the 16th to 18th centuries was followed by its introduction to Asia in the late 19th century from the New World or from now extinct populations in the Mediterranean Basin.Aedes mascarensisis a genetically distinct sister species toAe. aegyptis.l. This study provides a reference database of genetic diversity that can be used to determine the likely origin of new introductions that occur regularly for this invasive species. The genetic uniqueness of many populations and regions has important implications for attempts to controlAe. aegypti, especially for the methods using genetic modification of populations.
Developmental change in translation initiation alters the localization of a common microbial protein necessary for Toxoplasma chronic infection
Authors: Milligan‐Myhre Kathryn , Wilson Sarah K. , Knoll Laura J.
Published: September 2016

The Toxoplasma gondii cyst stage is resistant to drug therapy. To identify potential targets for new therapeutics, we screened insertional mutants of T. gondii for a reduced ability to form cysts in the brains of mice. In one of these mutants, named 38C3, the mutagenesis plasmid inserted into the mRNA of a protein that is highly conserved in microbes but is not present in humans. The mutation in 38C3 causes reduced brain cyst production during chronic infection, but does not affect acute virulence, so the disrupted gene and protein are called T. gondii Brain Colonization Protein 1 (TgBCP1). TgBCP1 has three potential in frame start codons that produce 51, 33 or 25 kDa proteins. In rapidly replicating tachyzoites, translation initiates at the third methionine, producing the 25 kDa form that is conserved in many bacteria and protozoans. Brain cysts exclusively express the 51 kDa form of TgBCP1, which is secreted from the parasites and localizes to the cyst wall. Only expression of the long form of TgBCP1 restored cyst formation in the 38C3 mutant. TgBCP1 is essential for cyst formation and is the first example of a developmental regulation in translation initiation site preference for a T. gondii protein.
Characterization of Pectobacterium carotovorum proteins differentially expressed during infection of Zantedeschia elliotiana in vivo and in vitro which are essential for virulence
Authors: Wang Huan , Yang Zhongling , Du Shuo , Ma Lin , Liao Yao , Wang Yujie , Toth Ian , Fan Jiaqin
Published: September 2016

The identification of phytopathogen proteins that are differentially expressed during the course of the establishment of an infection is important to better understand the infection process. In vitro approaches, using plant extracts added to culture medium, have been used to identify such proteins, but the biological relevance of these findings for in planta infection are often uncertain until confirmed by in vivo studies. Here, we compared the proteins of Pectobacterium carotovorum ssp. carotovorum strain PccS1 differentially expressed in Luria–Bertani medium supplemented with extracts of the ornamental plant Zantedeschia elliotiana cultivar ‘Black Magic’ (in vitro) and in plant tissues (in vivo) by two‐dimensional electrophoresis coupled with mass spectrometry. A total of 53 differentially expressed proteins (>1.5‐fold) were identified (up‐regulated or down‐regulated in vitro, in vivo or both). Proteins that exhibited increased expression in vivo but not in vitro, or in both conditions, were identified, and deletions were made in a number of genes encoding these proteins, four of which (clpP, mreB, flgK and eda) led to a loss of virulence on Z. elliotiana, although clpP and mreB were later also shown to be reduced in growth in rich and minimal media. Although clpP, flgK and mreB have previously been reported as playing a role in virulence in plants, this is the first report of such a role for eda, which encodes 2‐keto‐3‐deoxy‐6‐phosphogluconate (KDPG) aldolase, a key enzyme in Entner–Doudoroff metabolism. The results highlight the value of undertaking in vivo as well as in vitro approaches for the identification of new bacterial virulence factors.
A comparative study of renal care in Brazil and Mexico: hemodialysis treatment from the perspective of ESRD sufferers
Authors: Mercado‐Martinez Francisco J. , da Silva Denise Guerreiro V. , Correa‐Mauricio Mauricio E.
Published: September 2016

Renal replacement therapy is the indicated treatment for individuals with chronic kidney disease (CKD) to survive. However, not all sick people have access to the same treatment. This study compares renal care in two developing countries with different health systems. Specifically, it explores hemodialysis treatment from the perspective of low‐income individuals. A qualitative, comparative study was performed in Brazil and Mexico. Using purposive sampling, the research was based on open‐ended interviews with nineteen participants with kidney failure undergoing hemodialysis treatment in public hospitals and ten relatives. According to our results, Brazilian participants perceived hemodialysis care as satisfactory because of health personnel courtesy as well as free access to dialysis treatment, prescription drugs, hospitalization and transportation. However, they reported deficiencies in the care they were receiving due to shortages of specialists, prescription drugs, laboratory tests and transportation. Mexican participants, in contrast, highlighted the catastrophic costs of medical care because they had no free access to renal therapy, nor adequate financial resources. Our findings suggest that low‐income Brazilian CKD sufferers experience renal care differently, as they are more satisfied and face less obstacles with hemodialysis compared with those of Mexico. More studies on the topic are needed.