bluuebunny/crossref_metadata_2025 huggingface dataset:
PANTOPRAZOLE PHARMACOKINETICS IN OBESITY: WHERE GENES AND SIZE COLLIDE
Authors: Shakhnovich Valentina , Abdel-Rahman Susan , Friesen Craig , Pearce Robin , Gaedigk Andrea , Leeder J. Steven , Kearns Gregory
Published: December 2015

Background

Limited dosing guidelines exist for overweight children (≈30% pediatric population). This prospective study examines the pharmacokinetics (PK) of pantoprazole (CYP2C19 substrate) in overweight vs. normal-weight children.

Methods

Using TaqMan techniques, 51 children (6–17 yrs) were genotyped for CYP2C19 loss-of-function (*2, *3, *4) and gain-of-function (*17) alleles. After a single oral dose of pantoprazole (1.2 mg/kg lean body weight), 10 plasma samples were collected over 8hrs, pantoprazole/metabolite concentrations measured by HPLC-UV, and PK parameters generated via non-compartmental methods. Using a two-tailed unpaired t-test, parameters were compared between overweight/obese (n=24) and normal-weight (n=25) children, and the effect of CYP2C19 genotype (*1/*1, n=24; *1/*17, n=15; *1/*2, n=7; *2/*17, n=3; *2/*2, n=2) on drug disposition was analyzed using a one-way ANOVA; α=0.05.

Results

Dose-adjusted AUCtot, CL/F and other PK parameters were not significantly different between overweight/obese and normal-weight children. Independent of weight, mean AUCtot for pantoprazole was 2-fold greater in children with 1 loss-of-function vs. 1 gain-of-function allele (p=0.01). CL/F was increased only in children with *1/*17 genotype compared to all other genotypes (p<0.03), except *2/*17. In children with *1/*1 genotype (n=24), CL/F was significantly reduced (0.25±0.1 vs. 0.41±0.23 L/h/kg; p<0.05) and AUCtot increased (5.3±3.5 vs. 3.1±1.5 mg*h/L; p=0.05) in overweight/obese vs. normal-weight children. AUCtot was significantly increased in obese vs. normal-weight children (8.1±4.6 vs. 3.1±1.5 mg*h/L; p<0.05), with a positive correlation observed between AUCtot and BMI (r2=0.4; p=0.01).

Conclusions

CYP2C19 genotype appears to be the primary determinant of pantoprazole PK in children, whereas BMI may explain individual variability within genotype groups.
AUGMENTED RENAL CLEARANCE IMPLIES A NEED FOR INCREASED AMOXICILLIN-CLAVULANATE DOSING IN CRITICALLY ILL CHILDREN
Authors: Cock Pieter De , Standing Joseph , Barker Charlotte , de Jaeger Annick , Carlier Mieke , Dhont Evelyn , Verstraete Alain , Delanghe Joris , Robays Hugo , Paepe Peter De
Published: December 2015

Background

Amoxicillin/clavulanate is commonly used to treat community-acquired infections on the pediatric intensive care unit. Few data are available to guide dosing in this vulnerable population.

Methods

This prospective pharmacokinetic study enrolled patients admitted to the pediatric intensive care unit in whom intravenous amoxicillin-clavulanate was indicated (25–35 mg/kg q6h). Serial blood samples were obtained following the first and steady-state doses and amoxicillin/clavulanate concentrations were measured by a validated high-pressure liquid chromatography (HPLC)-tandem mass spectrometry method. Population pharmacokinetic analysis and Monte Carlo simulations were conducted using NONMEM’ 7.3.

Results

Three hundred twenty-five amoxicillin and 151 clavulanate blood samples were collected from 50 patients with a median age of 2.58 years (range: 0.08–15 years). A 3-compartment model for amoxicillin and a two-compartment model for clavulanate best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, serum Cystatin C (sCysC) ‘as a marker for renal function’ and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanate were 17.97 L/H/70 kg (95% CI:15.33–21.30 L/H/70 kg) and 12.20 L/H/70 kg (95% CI:10.54–14.55 L/H/70 kg), respectively. Four hourly dosing of 25 mg/kg (based on the amoxicillin component) was required to achieve 40% of the dosing interval for amoxicillin concentrations to be above MIC, and for clavulanate levels to be maintained above 2 mg/L. For patients with augmented renal function a 1 hour infusion was preferable to bolus dosing to achieve the therapeutic target.

Conclusions

Current dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks treatment failure in critically ill children.
POSSIBLE CONFOUNDERS IN THE REPORTED ASSOCIATION BETWEEN AUTISM SPECTRUM DISORDER (ASD) AND EXPOSURE TO SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS) DURING PREGNANCY
Authors: Bruyne Pauline De , Barzilay Eran , Koren Gideon
Published: December 2015

Background

Autism has been in the forefront of public concern because of reported increase in prevalence and growing interest in the role of environmental risk factors in autism. A recent meta-analysis by Man et al. (2015) reported an increased risk of ASD in children of mothers exposed to SSRIs during pregnancy (adjusted OR 1.81, 95% CI 1.47–2.24). However, association may not imply a causal relation between SSRI exposure and ASD. We hypothesize that underlying disease might have confounded the published result.

Materials and methods

A literature review was performed in order to identify possible confounders in the reported association. The list of search terms included but was not limited to following terms: ‘Pregnancy', ‘maternal', ‘depression', ‘child behaviour', ‘health care seeking behaviour'.

Results

Retrieved articles were classified in following four domains of possible confounders: 1/ direct link between depression and ASD, 2/effect of depression on interaction with the child, 3/effect of depression on other risk factors of ASD and 4/ascertainment bias. In the last domain, we examined the effect of depression on the way mothers perceive and report on the behaviour of their child and the effect of maternal depression on healthcare seeking behaviour. Analysis suggests that there are important merits to all those four domains.

Conclusion

Because of obvious ethical reasons, research on exposure during pregnancy is mostly restricted to systematic review and meta-analysis of observational studies. Although this has resulted in a treasury of information, possible confounders must be taken into account when interpreting the results.
HEPATIC TRANSPORTER PROTEIN EXPRESSION IN FETUSES, NEONATES AND YOUNG INFANTS
Authors: Mooij Miriam , de Steeg Evita Van , Wortelboer Heleen , Vaes Wouter , Tibboel Dick , Wildt Saskia De
Published: December 2015

Background

Transporters are membrane-bound proteins involved in trafficking substrates (e.g. drugs) across membranes of among others hepatocytes. Limited data exists on the developmental expression. We aim to study protein expression of transporters in fetal, neonatal and infantile liver.

Methods

Transporter protein expression (ABCB1, ABCG2, ABCC2, ABCC3, BSEP, GLUT1, MCT1, OATP1B1, OATP2B1, OCTN2) was quantified using UPLC-MS-MS, on snap-frozen post mortem livers (Erasmus MC tissuebank) and adult control livers (UMC-Groningen). Protein expression was determined in isolated crude membrane and quantified using stable-isotope-labelled peptides. Age groups were compared with Mann-Whitney test and post hoc Bonferroni-correction (significance p<0.05). Data was compared to mRNA expression.

Results

25 liver samples were studied. 10 fetal [median gestational age 23.2 weeks (range 16.4–37.9)], 12 pediatric [postnatal age 1 week (0–11.4) and gestational age at birth 35.1 weeks (27.1–41.0)], and 3 adult liver samples. ABCB1, ABCC2, OATP1B1, OATP2B1 expressions appeared similar in fetuses, pediatrics and adults. MCT1 expression was similar in fetuses and adults, but higher in pediatrics. BSEP expression was lower in fetuses and pediatrics than in adults. ABCC3 expression was lower level in fetuses than in adults, but not in pediatrics compared to adults. ABCG2, GLUT1, OCTN2 expressions were higher in fetuses than in adults, but similar in pediatrics and adults.

Conclusion

Hepatic transporters appear in different developmental expression profiles. ABCB1, ABCC2, OATP1B1 protein expression appears stable. This contrast previous mRNA expression data, which showed lower expression in fetus/neonate. The age-related differences in transporter expression may result in age-dependent pharmacokinetics of substrates.
DRUG PRESCRIPTION PROFILE AND PERINATAL DETERMINANTS DURING THE FIRST YEAR OF LIFE
Authors: Piovani Daniele , Clavenna Antonio , Pavoni Chiara , Bonati Maurizio
Published: December 2015

The aim of the study was to investigate the drug prescription profile during the first year of life in a cohort of newborns, and the influence of perinatal and socio-demographic factors on drug prescription.

A total of 61,479 neonates born in 2011 were included. The data source was the database of reimbursed prescriptions of the Lombardy region, Italy. Drug prescriptions were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. Drug prevalence was calculated as the percentage of neonates receiving at least one drug prescription in one year. Chi-square test was used to compare prevalence of drug prescription in males and females.

In all, 42,204 infants (68.7%) received at least one drug prescription, with a prevalence slightly higher in males than females (71.1% versus 66.1%; χ2=178 p<0.01). The drug classes most commonly prescribed in the first year of life were antibiotics (39.5% of infants), anti-asthmatics (32.6%), and corticosteroids for systemic use (9.8%).

The median age of first prescription was 20.6 (Interquartile range: 9.4–33.3) weeks. Males received the first prescription about one week before females (20.1 versus 21.3, respectively). The first prescription concerned mainly anti-asthmatics (40.5%), and antibiotics (37.9%), and amoxicillin (16.3%), beclomethasone (16.0%), and amoxicillin+clavulanic acid (15.0%) were the most prescribed drugs.

In conclusion, in the first year of life, 7 out of 10 infants received drug prescriptions. Males were more exposed than females, a finding consistent with the epidemiology of diseases in infancy. The analysis concerning the influence of maternal and perinatal factors is ongoing.
ALPROSTADIL ASSOCIATED FEVER IN THE NEWBORN: SIDE EFFECT OR INFECTION?
Authors: Swaid Sohair Bshara , Vardi Amir , Perlman Amichai , Matok Ilan
Published: December 2015

Background

Alprostadil is a prostaglandin used to maintain patent ductus arteriosus in neonates with ductus arteriosus dependent congenital heart malformations. Alprostadil administration results in fever in ∼14% of treated neonates. The occurrence of fever in this setting, often leads to extensive investigations to identify the source of fever, as well as to empiric antibiotic therapy and the postponement of cardiac surgery. These measures can lead to several neonatal complications.

Aim

To identify clinical and laboratory criteria that can help determine the likelihood that fever during alprostadil therapy is due to infection.

Methods

Using a case control study design, we evaluated neonates who were admitted to the pediatric cardiac intensive care department between 2009 and 2014, and who developed fever during alprostadil treatment. Neonates with infection and without were compared to identify early clinical symptoms and biomarkers that can serve as predictors of infection. Analyses included univariate and multivariate methods.

Results

Our study included 124 neonates. Seventy neonates experienced infection (median age 9 days (IQR 4–15.2)) and fifty-four did not (median age 5 days (IQR 2–11)). Factors preceding fever and predicting infection included: White blood cell count (WBC) above 10000/microL (HR=1.97, 95% CI 1.02–3.74), or platelet count above 440 K/microL (HR=2.27, 95%CI=1.32–5.23). Increases in WBC or lactate, before fever onset, were also associated with infection.

Conclusions

Elevations in WBC, platelets and lactate before fever onset were associated with infection. These results may assist in decisions regarding cardiac surgery timing in neonates treated with alprostadil.
RISK FACTORS FOR NODAT UNDER IMMUNOSSUPPRESSANTS IN RENAL TRANSPLANTED CHILDREN
Authors: Lancia Pauline , Zhao Wei , Maisin Anne , Simon Dominique , Elie Veronique , Elie Valery , Jacqz-Aigrain Evelyne
Published: December 2015

Introduction

New Onset Diabetes After Transplantation (NODAT) is a major complication of immunossuppressive therapy and an risk factor for transplant rejection. Its incidence ranges from 4 to 25% in adults. In 2013, L. Elens and coworkers reported the association of two genetic variants PPARα rs4253728 and POR*28 rs1057868 with the occurrence of NODAT in renal transplanted adults treated with tacrolimus, MMF and corticosteroïds.

Objective

Our objective was to assess the impact of these two genetics variants along with additional risk factors (age, sex, HLA missmatches…) on the occurrence of NODAT among renal transplanted children treated with tacrolimus, MMF, and corticoids.

Materiel and method

Genotypes were determined using allelic discrimination technique. The univariate and mulivariate analyses have been performed using SPSS v15.

Results

238 renal transplanted children were identified between 1990 and 2013, 109 were treated with tacrolimus and included in the study (63 boys/46 girls). The mean age at time of transplantation was 10.8 years (±0.5) and mean duration of floow-up was 4 years (±0.3). A significant association of NODAT was evidenced with POR*28 (p=0.010) but not with PPARα (p=0.434), number of HLA mismatches (p=0.004) and donor's CMV serology (p=0.026).

Conclusion

This pilot study validated the association between the SNP POR*28 and the occurrence of NODAT in renal transplanted children treated with tacrolimus. Early identification of patients carrying POR*28 genetic variant might allow to anticipate the risk of NODAT and improve patient's care.
PULMONARY HYPERTENSION IN PAEDIATRIC PATIENTS: DATA FROM THE COMPERA-KIDS REGISTRY
Authors: Gorenflo Matthias , Pittrow David , Huscher Dörte , Ziesenitz Victoria , Pattathu Joseph , Praus Alexander , Ewert Peter , Kaemmerer Harald , Group COMPERA-Kids Steering Committee Stu
Published: December 2015

Background

Pulmonary hypertension (PH/PAH) can have many possible causes in childhood. The aim of the COMPERA registry is the characterization of patients of all ages with PH/PAH and their treatment patterns.

Methods

Since June 2013, paediatric patients can be included in the COMPERA registry (ClinTrials.gov: NCT01347216) which has originally been established for adult patients with pulmonary hypertension in 2007.

Results

Until 2015, 78 patients <18 years (47 Pat <6 years) with pulmonary hypertension were enrolled, of whom 65.4% had PAH due to congenital heart disease (PAH-CHD), 25.6% had idiopathic PAH (iPAH), 3 had persistent PH of the newborn, 2 had PH associated with interstitial lung disease, and two had other PH. The patients were 6.1±6.0 years old, 52.6% girls; NYHA functional class I/II in 55.0%, and III in 42.3%. Mean disease duration after diagnosis was 37.7±55.8 months. Right heart catheterization data were available for 82.1% of the patients. Mean pulmonary artery pressure was 42.8±19.4 mmHg, right atrial pressure was 8.0±8.8 mmHg, cardiac index was 3.6±1.2 l/min/m2. Monotherapy was received by 65.4% of the patients whereas 33.4% of the patients had combination therapy. Phosphodiesterase-5 inhibitors (PDE5I) were administered to 76.9% of the patients, 35.9% of the patients received endothelin receptor antagonists and 3.8% received prostacyclins. About 24% of patients received anticoagulation therapy.

Conclusion

The most common form of PH in this study cohort is PAH-CHD, followed by iPAH. Treatment options for children primarily comprise PDE5I. Only a small number of paediatric patients receive anticoagulation therapy.
RISKS IN PHARMACOLOGICAL TREATMENT OF PEDIATRIC INPATIENTS–THE DOCTORś AND NURSEŚ VIEWS
Authors: Lilja Lina , Garnemark Christiane , Kindblom Jenny
Published: December 2015

Background

Medication errors in pediatric care are common and clinically important. The greatest risk of error occurs during drug prescription and administration of medicines. Medication errors can be prevented if potential sources of error are identified and addressed.

Objective

Explore and describe the physicians' and nurses' views on the risks regarding pharmacological treatment of pediatric inpatients. Find out what the obstacles might be for the staff in their work with prescription, preparation and administration of medicines, and what might constitute help and improvements to reduce medical errors.

Method

We used three different methods to identify and describe the risks of pharmacological treatment at the department of pediatrics at Queen Silviás Children's Hospital in Gothenburg; reports from the medical error report system MedControl, targeted interviews with nurses and doctors and a questionnaire survey to all doctors and nurses.

Results

The study revealed three main problem entities; difficulties related to drug prescription and the IT-system for computerized prescriptions, a need for improved support systems for drug prescriptions and administration as well as hazards relating to work environment such as disturbances, lack of time, and high staff turnover.

Conclusion

Drug treatment for children is a delicate matter that places high demands on everyone involved. A pressured work environment, incomplete IT systems and gaps in supports system for drug prescription and administration are unnecessary risks. To overcome these difficulties we propose extended local prescription and administration support, coordination of procedures between wards and development of IT systems adapted to the specific needs in pediatrics.
UNINTENTIONAL OVERDOSING OF INTRAVENOUS PARACETAMOL IN NEONATES: WHERE IS THE TOXICITY?
Authors: Bosch Barbara , Casteels Kristina , Allegaert Karel
Published: December 2015

Introduction

Paracetamol is a readily available antipyretic and analgesic, widely used to treat mild to moderate pain. Unintentional overdosing in neonates occurs, but so far only single case reports have been published. Based on an own case and a bibliographic search, we review the safety and tolerance of unintentiontal overdosing of intravenous paracetamol in neonates.

Material and methods

A bibliographic search in PubMed and EMBASE using key words: “Pharmacokinetics paracetamol neonate”, “Metabolism paracetamol neonate” and “Effects paracetamol neonate” was performed.

Results

Thirty cases of neonatal iv paracetamol intoxication were reported. Overall, the reported number remains limited, but even 10-fold drug errors only rarely result in significant morbidity or mortality. In accidental overdosing only one case of relevant hepatic toxicity has been reported.

Conclusion

The reported cases of unintentional paracetamol overdosing in neonates suggests a good safety profile and a population specific tolerance. Acetylcysteine administration is recommended, but the prognosis seems to be better in neonates.
EXTENDED INTERVAL GENTAMICIN DOSING IN PRETERM INFANTS LESS THAN 35 WEEKS CORRECTED GESTATIONAL AGE
Authors: McKitrick Jarrid W R , Bewick Brad , Ariano Robert , Zelenitsky Sheryl , Narvey Michael , Jong Geert W 't
Published: December 2015

Objective

To confirm that gentamicin 5 mg/kg/dose every 48 hours in neonates less than 35 weeks corrected gestational age (CGA) results in the majority of gentamicin serum trough levels within the range of 0.5–2 mg/L and peak levels within the range of 6–12 mg/L.

Design

Prospective pharmacokinetic (PK) analysis.

Setting

Two neonatal intensive care units and one intermediate care unit in two tertiary care centres. Patients: Neonates less than 35 weeks CGA who received empiric gentamicin for sepsis between March 10 and June 10, 2014 in whom at least one gentamicin serum level was measured. Methods: PK analysis was performed following implementation of empiric dosing for gentamicin of 5 mg/kg every 48 hours in neonates.

Results

Mean Cl, t1/2 and V1 were 42±10 mL/kg/h, 10.0±1.8 h, and 0.58±0.09 L/kg, respectively (n=54). A one-compartment pharmacokinetic model best represented the data. The mean Cl of gentamicin at 24 h post dose was significantly lower in neonates.

Conclusions

Gentamicin 5 mg/kg q48h results in serum post dose levels between 6–12 mg/L 98% of the time compared to 5% of the time for once daily doses of 2.5 or 3 mg/kg. Gentamicin doses of 5 mg/kg q48h resulted in serum pre levels less than 0.5 mg/L 82% of the time (48 h post dose) compared to 9% of the time for once daily doses (24 h post dose). Increased clearance with advanced PNA suggests the need for more frequent dosing in neonates >14 days of age.
FLUOROQUINOLONES IN PEDIATRIC PATIENTS: NO MORE “OFF-LABEL USE”
Authors: Dinavitser Natalie , Berlin Maya , Miller Reuven , Finkel-Pekarsky Victoriya , Berkovitch Matitiahu
Published: December 2015

Fluoroquinolones (FQs) are used in pediatric patients worldwide. However, due to cartilage damage in young animals they are not approved for children under 18 years of age for most indications. Major regulatory authorities such as EMA, FDA, UK, Ireland, NZ and Australia indicate that FQs are contraindicated in children. Ciprofloxacin and levofloxacin can be prescribed to children, but only for a few indications. As a result, FQs are used “off-label” in this population. From our experience, we believe that FQs should not be contraindicated in children. However, evidence-based data is needed.

Objective

To investigate whether FQ use in children may cause musculoskeletal adverse reactions (ADRs).

Methods

We reviewed the Israel Ministry of Health ADR reporting system and VigiLyze (WHO reporting system) for musculoskeletal ADRs due to FQs in children. A literature search– Medline, Pubmed, Cochraine database and pharmacologic textbooks, for musculoskeletal ADRs among FQ treated pediatric patients was conducted. Terms used: Fluoroquinolones, ciprofloxacin, levofloxacin, ofloxacin, arthropathy, tendinophaty, arthralgia, children, pediatric use.

Results

During the period 1968 to Feb 2015, the Israeli MOH did not receive spontaneous reports regarding FQs in children. The VigiLyze program identified 192 ADR reports in children related to FQs: arthralgia, arthropathy, myalgia, and tendon injury. Most ADRs were transient and reversible. The literature search indicated that although musculoskeletal ADRs are not uncommon, they are mild, transient, and not necessarily due to FQs. Joint MRI, performed in some of the studies, did not reveal cartilage damage.

Conclusions

FQs should be registered for pediatric patients as for adults.
Airway management of a life-threatening post-thyroidectomy haematoma
Authors: Adigbli George , King Jonathan
Published: December 2015

Neck haematomas are rare but potentially life-threatening complications of thyroid surgery. Postoperative monitoring, early diagnosis and immediate management are critical, as this condition can rapidly lead to compression and obstruction of the upper airway. We present a case of a 69-year-old woman who suffered respiratory failure resulting from a post-thyroidectomy haematoma with airway obstruction and severe haemodynamic compromise, presenting a difficult anaesthetic challenge. Following development of a likely ‘cannot intubate, cannot ventilate’ situation despite haematoma evacuation, the patient underwent emergency cricothyroidotomy, before rapid sequence intubation and subsequent surgical haemostasis.
Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study
Authors: Patel Rashmi , Reiss Peter , Shetty Hitesh , Broadbent Matthew , Stewart Robert , McGuire Philip , Taylor Matthew
Published: December 2015

Objectives

To investigate the association between antidepressant therapy and the later onset of mania/bipolar disorder.

Design

Retrospective cohort study using an anonymised electronic health record case register.

Setting

South London and Maudsley National Health Service (NHS) Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK.

Participants

21 012 adults presenting to SLaM between 1 April 2006 and 31 March 2013 with unipolar depression.

Exposure

Prior antidepressant therapy recorded in electronic health records.

Main outcome measure

Time to subsequent diagnosis of mania or bipolar disorder from date of diagnosis of unipolar depression, censored at 31 March 2014.

Methods

Multivariable Cox regression analysis with age and gender as covariates.

Results

The overall incidence rate of mania/bipolar disorder was 10.9 per 1000 person-years. The peak incidence of mania/bipolar disorder incidence was seen in patients aged between 26 and 35 years (12.3 per 1000 person-years). Prior antidepressant treatment was associated with an increased incidence of mania/bipolar disorder ranging from 13.1 to 19.1 per 1000 person-years. Multivariable analysis indicated a significant association with selective serotonin reuptake inhibitors (HR 1.34, 95% CI 1.18 to 1.52) and venlafaxine (1.35, 1.07 to 1.70).

Conclusions

In people with unipolar depression, antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These findings highlight the importance of considering risk factors for mania when treating people with depression.
Associations between stress disorders and cardiovascular disease events in the Danish population
Authors: Gradus Jaimie L , Farkas Dóra Körmendiné , Svensson Elisabeth , Ehrenstein Vera , Lash Timothy L , Milstein Arnold , Adler Nancy , Sørensen Henrik Toft
Published: December 2015

Objectives

Post-traumatic stress disorder (PTSD) is a well-documented risk factor for cardiovascular disease (CVD). However, it is unknown whether another common stress disorder—adjustment disorder—is also associated with an increased risk of CVD and whether gender modifies these associations. The aim of this study was to examine the overall and gender-stratified associations between PTSD and adjustment disorder and 4 CVD events.

Design

Prospective cohort study utilising Danish national registry data.

Setting

The general population of Denmark.

Participants

PTSD (n=4724) and adjustment disorder (n=64 855) cohorts compared with the general population of Denmark from 1995 to 2011.

Primary outcome measures

CVD events including myocardial infarction (MI), stroke, ischaemic stroke and venous thromboembolism (VTE). Standardised incidence rates and 95% CIs were calculated.

Results

Associations were found between PTSD and all 4 CVD events ranging from 1.5 (95% CI 1.1 to 1.9) for MI to 2.1 (95% CI 1.7 to 2.7) for VTE. Associations that were similar in magnitude were also found for adjustment disorder and all 4 CVD events: 1.5 (95% CI 1.4 to 1.6) for MI to 1.9 (95% CI 1.8 to 2.0) for VTE. No gender differences were noted.

Conclusions

By expanding beyond PTSD and examining a second stress disorder—adjustment disorder—this study provides evidence that stress-related psychopathology is associated with CVD events. Further, limited evidence of gender differences in associations for either of the stress disorders and CVD was found.
Cancer treatment decision-making processes for older patients with complex needs: a qualitative study
Authors: Bridges Jackie , Hughes Jane , Farrington Naomi , Richardson Alison
Published: December 2015

Objectives

Although older people can experience complex health and social care needs alongside a primary cancer diagnosis, little is understood about how cancer treatment decisions are made for this population. This study aimed to investigate how cancer treatment decisions are formulated for older people with complex health and social care needs and the factors that shape these processes.

Design

Qualitative study involving semistructured interviews and non-participant observations. Framework approach used for data analysis.

Setting

Breast and colorectal cancer services in five English NHS hospital trusts.

Participants

Interviews: purposive sample of 22 clinicians directly involved in a face-to-face clinical role with patients regarding cancer treatment and care, maximising variation across clinical roles, tumour types and trusts. Observations: purposive sample of five cancer multidisciplinary meetings, maximising variation across location, team size and tumour type.

Results

The initial stages of cancer treatment decision-making are team-based, medically dominated and focused on the cancer. For patients with complex health and social care needs that extend beyond cancer pathology, later and less visible stages in the decision-making process are more haphazard and may result in less effective and workable treatment plans, as individual clinicians struggle to devise and deliver these plans without breaching time-based targets.

Conclusions

Service targets that focus resources solely on the presenting disease can disadvantage older patients with complex health and social care needs that extend beyond this primary diagnosis. Care should be taken to ensure time-based targets do not disincentivise thorough and timely assessment that can lead to the formulation of treatment plans tailored to individual needs and circumstances.
Oesophageal spasm, vomiting and hyoscine hydrobromide patch
Authors: Murray-Brown Fay , Davies I Llion
Published: December 2015

We report the case of a 60-year-old woman with metastatic breast cancer whose intractable nausea and vomiting were effectively managed with a hyoscine hydrobromide (scopolamine) patch. Contrast swallow revealed oesophageal spasm to be the underlying cause. Symptom relief may be attributed to the antimuscarinic properties of the patch, allowing lower oesophageal sphincter relaxation. Following patch use she was able to enjoy small meals and fluids without symptoms. This is the first time this mechanism of action of scopolamine for alleviating nausea and vomiting has been described in the literature.
Klotho expression in cervical cancer: differential expression in adenocarcinoma and squamous cell carcinoma
Authors: Aviel-Ronen Sarit , Rubinek Tami , Zadok Oranit , Vituri Aya , Avivi Camila , Wolf Ido , Barshack Iris
Published: December 2015

Aims

Klotho is a trans-membrane protein that serves as a tumour suppressor in a wide array of malignancies. Recent data suggest it as an epigenetically silenced tumour suppressor in cervical cancer. Yet, the expression pattern of klotho in cervical cancer has not been determined. We aimed to study the expression of klotho in squamous cell carcinomas (SQCC) and adenocarcinoma (ADC) of the cervix.

Methods

Klotho expression was analysed by immunohistochemistry in 44 SQCC samples, 38 ADC samples and the adjacent normal tissue. For each sample, percentage of positive stained cells, staining intensity and a combined staining score were recorded. Staining was validated by measuring klotho mRNA levels, using quantitative RT-PCR, in 18 of the samples.

Results

Klotho expression was high in all endocervical and exocervical normal tissues adjacent to tumour. No expression of klotho was noted in 7 out of 38 (18.4%) ADC samples and in 2 out of 44 (4.5%) SQCC samples. Staining intensity, number of positively stained cells and combined intensity score were all lower in tumours compared with normal adjacent tissues in ADC and SQCC. Klotho mRNA levels highly correlated with immunohistochemical (IHC) staining (p=0.008).

Conclusions

We found reduced klotho expression in cervical carcinoma, especially in ADC, compared with normal adjacent tissue. Our results support the role of klotho as a potential tumour suppressor in cervical cancer. Further studies are required in order to establish the therapeutic role of klotho in cervical carcinoma and identify patients who may benefit from it.
Eigenvalues of the drifted Laplacian on complete metric measure spaces
Authors: Cheng Xu , Zhou Detang
Published: December 2015

In this paper, first we study a complete smooth metric measure space [Formula: see text] with the ([Formula: see text])-Bakry–Émery Ricci curvature [Formula: see text] for some positive constant [Formula: see text]. It is known that the spectrum of the drifted Laplacian [Formula: see text] for [Formula: see text] is discrete and the first nonzero eigenvalue of [Formula: see text] has lower bound [Formula: see text]. We prove that if the lower bound [Formula: see text] is achieved with multiplicity [Formula: see text], then [Formula: see text], [Formula: see text] is isometric to [Formula: see text] for some complete [Formula: see text]-dimensional manifold [Formula: see text] and by passing an isometry, [Formula: see text] must split off a gradient shrinking Ricci soliton [Formula: see text], [Formula: see text]. This result can be applied to gradient shrinking Ricci solitons. Secondly, we study the drifted Laplacian [Formula: see text] for properly immersed self-shrinkers in the Euclidean space [Formula: see text], [Formula: see text] and show the discreteness of the spectrum of [Formula: see text] and a logarithmic Sobolev inequality.
Prediction of protein–protein interaction network using a multi-objective optimization approach
Authors: Chowdhury Archana , Rakshit Pratyusha , Konar Amit
Published: December 2015

Protein–Protein Interactions (PPIs) are very important as they coordinate almost all cellular processes. This paper attempts to formulate PPI prediction problem in a multi-objective optimization framework. The scoring functions for the trial solution deal with simultaneous maximization of functional similarity, strength of the domain interaction profiles, and the number of common neighbors of the proteins predicted to be interacting. The above optimization problem is solved using the proposed Firefly Algorithm with Nondominated Sorting. Experiments undertaken reveal that the proposed PPI prediction technique outperforms existing methods, including gene ontology-based Relative Specific Similarity, multi-domain-based Domain Cohesion Coupling method, domain-based Random Decision Forest method, Bagging with REP Tree, and evolutionary/swarm algorithm-based approaches, with respect to sensitivity, specificity, and F1 score.
KillerRed protein basedin vivophotodynamic therapy and corresponding tumor metabolic imaging
Authors: Lin Qiaoya , Sha Shuang , Yang Fei , Jin Honglin , Zhang Zhihong
Published: December 2015

Photodynamic therapy (PDT) gains wide attention as a useful therapeutic method for cancer. It is mediated by the oxygen and photosensitizer under the specific light irradiation to produce the reactive oxygen species (ROS), which induce cellular toxicity and regulate the redox potential in tumor cells. Nowadays, genetic photosensitizers of low toxicity and easy production are required to be developed. KillerRed, a unique red fluorescent protein exhibiting excellent phototoxic properties, has the potential to act as a photosensitizer in the application of tumor PDT. Meantime, the course of tumor redox metabolism during this treatment was rarely investigated so far. Thus here, we investigated the effects of KillerRed-based PDT on tumor growth in vivo and examined the subsequent tumor metabolic states including the changes of nicotinamide adenine dinucleotide hydrogen (NADH) and flavoprotein (Fp), two important metabolic coenzymes of tumor cells. Results showed the tumor growth had been significantly inhibited by KillerRed-based PDT treatment compared to control groups. A home-made cryo-imaging redox scanner was used to measure intrinsic fluorescence and exogenous KillerRed fluorescence signals in tumors. The Fp signal was elevated by nearly 4.5-fold, while the NADH signal decreased by 66% after light irradiation, indicating that Fp and NADH were oxidized in the course of KillerRed-based PDT. Furthermore, we also observed correlation between the fluorescence distribution of KillerRed and NADH. It suggests that the KillerRed protein based PDT might provide a new approach for tumor therapy accompanied by altering tumor metabolism.
The Comparison of Experiment Results and CFD Simulation in the Heat Pump System Using Thermobank and Two-Phase Ejector for Heating Room and Cold Storage
Authors: Cuong Le Ngoc , Oh Jong-Taek
Published: December 2015

In this paper, the heat pump system has been developed by CFD simulation and experimental investigation. It studies the thermal behavior of a thermobank and COP on heat pump system and cold storage. The thermobank stores the waste heat of during refrigeration cycles and this energy is used for defrosting process and heating room. It also reduces defrosting time and condensation load so that the temperature regulation in the cold storage is constant. The system is investigated experimentally and CFD simulated under thermobank. The dimension [Formula: see text] of cold storage is [Formula: see text][Formula: see text]m, thermobank is [Formula: see text][Formula: see text]mm. The temperature of ambient on CFD simulation process is 20[Formula: see text]C. This heat pump system can be used to keep preservation of agricultural products in cold storage warehouse together with floor panel heating for room in winter. The ejector is used in system with the aim of increasing coefficient of performance (COP) and decrease in compressor displacement. As the experimental results, its COP is increased about 38.57% when using thermobank and ejector in heat pump system.
CORDIC-Based Enhanced Systolic Array Architecture for QR Decomposition
Authors: Zhang Jianfeng , Chow Paul , Liu Hengzhu
Published: December 2015

Multiple input multiple output (MIMO) with orthogonal frequency division multiplexing (OFDM) systems typically use orthogonal-triangular (QR) decomposition. In this article, we present an enhanced systolic array architecture to realize QR decomposition based on the Givens rotation (GR) method for a 4 × 4 real matrix. The coordinate rotation digital computer (CORDIC) algorithm is adopted and modified to speed up and simplify the process of GR. To verify the function and evaluate the performance, the proposed architectures are validated on a Virtex 5 FPGA development platform. Compared to a commercial implementation of vectoring CORDIC, the enhanced vectoring CORDIC is presented that uses 37.7% less hardware resources, dissipates 71.6% less power, and provides a 1.8 times speedup while maintaining the same computation accuracy. The enhanced QR systolic array architecture based on the enhanced vectoring CORDIC saves 24.5% in power dissipation, provides a factor of 1.5-fold improvement in throughput, and the hardware efficiency is improved 1.45-fold with no accuracy penalty when compared to our previously proposed QR systolic array architecture.
Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD
Authors: Luo Yuwen , Burrington Christine M. , Graff Emily C. , Zhang Jian , Judd Robert L. , Suksaranjit Promporn , Kaewpoowat Quanhathai , Davenport Samantha K. , O'Neill Ann Marie , Greene Michael W.
Published: December 2015

nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model is currently in question. In our study, a high-fat Western diet (HFWD) with liquid sugar [fructose and sucrose (F/S)] induced acute hyperphagia above that observed in HFWD-fed mice, yet without changes in energy expenditure. Liquid sugar (F/S) exacerbated HFWD-induced glucose intolerance and insulin resistance and impaired the storage capacity of epididymal white adipose tissue (eWAT). Hepatic TG, plasma alanine aminotransferase, and normalized liver weight were significantly increased only in HFWD+F/S-fed mice. HFWD+F/S also resulted in increased hepatic fibrosis and elevated collagen 1a2, collagen 3a1, and TGFβ gene expression. Furthermore, HWFD+F/S-fed mice developed more profound eWAT inflammation characterized by adipocyte hypertrophy, macrophage infiltration, a dramatic increase in crown-like structures, and upregulated proinflammatory gene expression. An early hypoxia response in the eWAT led to reduced vascularization and increased fibrosis gene expression in the HFWD+F/S-fed mice. Our results demonstrate that sugary water consumption induces acute hyperphagia, limits adipose tissue expansion, and exacerbates glucose intolerance and insulin resistance, which are associated with NAFLD progression.
Rare Cause of Wide QRS Tachycardia
Authors: Mironov Nikolay Yu. , Mironova Natalia A. , Saidova Marina A. , Stukalova Olga V. , Golitsyn Sergey P.
Published: December 2015

Cardiac involvement is a well-known feature of neuromuscular diseases. Most commonly cardiac manifestations occur later in the course of the disease. Occasionally severe cardiac disease, including conduction disturbances, life-threatening arrhythmias, and cardiomyopathy, with its impact on prognosis, may be dissociated from peripheral myopathy. We report a case of bundle branch reentrant ventricular tachycardia as primary manifestation of myotonic dystrophy and discuss associated diagnostic and treatment challenges.
Biphasic Regulation of Lipid Metabolism: A Meta-Analysis of Icodextrin in Peritoneal Dialysis
Authors: Huang Yan-Feng , Zhu Da-Jian , Chen Xiao-Wu , Ouyang Man-Zhao , Zhang Wei-Jie
Published: December 2015

Objectives. The objective of this systematic meta-analysis was to study the impact of icodextrin (ICO) on lipid profiles.Methods. MEDLINE, PubMed, Embase, Chinese Biomedical Literature, and the Cochrane Library and Reference lists were searched (last search September 2014) in accordance with the Cochrane Handbook for Systematic Reviews of Interventions.Results. Searches identified 13 eligible trials with a total of 850 patients. The differentials of total cholesterol (TC) and free fatty acid (FFA) in the ICO group were greater than those in the GLU group. Metaregression analysis showed that TC levels positively correlated with its baseline levels. In the subgroup of patients with dialysis duration more than 6 months, TC and TG in the ICO group were less. In pooled data from cross-sectional studies, differential of TG in the ICO group was less. In the subgroup of patients with diabetes (Martikainen et al., 2005, Sniderman et al., 2014, and Takatori et al., 2011), differential of high-density lipoprotein cholesterol (HDL-C) in the ICO group was less. There was no significant effect on low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), or lipoprotein(a).Conclusions. ICO may be beneficial to lipid metabolism, especially for its biphasic regulation of plasma TC levels.
Relationship between Pain and Medial Meniscal Extrusion in Knee Osteoarthritis
Authors: Kijima Hiroaki , Yamada Shin , Nozaka Koji , Saito Hidetomo , Shimada Yoichi
Published: December 2015

Purpose. In knee osteoarthritis, the degree of pain varies despite similar imaging findings. If there were quantitative findings related to the pain of knee osteoarthritis, it could be used for diagnosis or screening. The medial meniscal extrusion was investigated as a candidate quantitative finding related to the pain of knee osteoarthritis.Methods. Seventy-six knees of 38 patients (mean age, 73 years) who received intra-articular injections of hyaluronic acid into unilateral knees at the time of diagnosis of knee arthritis were investigated. Cartilage thickness of the femoral medial condyle and medial meniscal extrusion of bilateral knees were measured by ultrasonography. Thirty-eight knees that had hyaluronic acid injections were compared with 38 other side knees from the same patients as the control group.Results. The average cartilage thicknesses of the knees with pain that received intra-articular injections and the knees without pain that received no injections were 1.02 and 1.05 mm, respectively (P=0.6394). On the other hand, the average medial meniscal extrusions of the knees with and without pain were 7.58 and 5.88 mm, respectively (P=0.0005); pain was associated with greater medial meniscal extrusions.Conclusion. Medial meniscal extrusion is a quantitative finding related to the pain of knee osteoarthritis.
The Dirichlet Problem for Second-Order Divergence Form Elliptic Operators with Variable Coefficients: The Simple Layer Potential Ansatz
Authors: Cialdea Alberto , Leonessa Vita , Malaspina Angelica
Published: December 2015

We investigate the Dirichlet problem related to linear elliptic second-order partial differential operators with smooth coefficients in divergence form in bounded connected domains ofRm(m≥3) with Lyapunov boundary. In particular, we show how to represent the solution in terms of a simple layer potential. We use an indirect boundary integral method hinging on the theory of reducible operators and the theory of differential forms.
Effects of Abiotic Factors on HIPV-Mediated Interactions between Plants and Parasitoids
Authors: Becker Christine , Desneux Nicolas , Monticelli Lucie , Fernandez Xavier , Michel Thomas , Lavoir Anne-Violette
Published: December 2015

In contrast to constitutively emitted plant volatiles (PV), herbivore-induced plant volatiles (HIPV) are specifically emitted by plants when afflicted with herbivores. HIPV can be perceived by parasitoids and predators which parasitize or prey on the respective herbivores, including parasitic hymenoptera. HIPV act as signals and facilitate host/prey detection. They comprise a blend of compounds: main constituents are terpenoids and “green leaf volatiles.” Constitutive emission of PV is well known to be influenced by abiotic factors like temperature, light intensity, water, and nutrient availability. HIPV share biosynthetic pathways with constitutively emitted PV and might therefore likewise be affected by abiotic conditions. However, the effects of abiotic factors on HIPV-mediated biotic interactions have received only limited attention to date. HIPV being influenced by the plant’s growing conditions could have major implications for pest management. Quantitative and qualitative changes in HIPV blends may improve or impair biocontrol. Enhanced emission of HIPV may attract a larger number of natural enemies. Reduced emission rates or altered compositions, however, may render blends imperceptible to parasitoides and predators. Predicting the outcome of these changes is highly important for food production and for ecosystems affected by global climate change.
Distribution of Phenolic Contents, Antidiabetic Potentials, Antihypertensive Properties, and Antioxidative Effects of Soursop (Annona muricataL.) Fruit PartsIn Vitro
Authors: Adefegha Stephen A. , Oyeleye Sunday I. , Oboh Ganiyu
Published: December 2015

Soursop fruit has been used in folklore for the management of type-2 diabetes and hypertension with limited information on the scientific backing. This study investigated the effects of aqueous extracts (1 : 100 w/v) of Soursop fruit part (pericarp, pulp, and seed) on key enzymes linked to type-2 diabetes (α-amylase andα-glucosidase) and hypertension [angiotensin-I converting enzyme (ACE)]. Radicals scavenging and Fe2+chelation abilities and reducing property as well as phenolic contents of the extracts were also determined. Our data revealed that the extracts inhibitedα-amylase andα-glucosidase and ACE activities dose-dependently. The effective concentration of the extract causing 50% antioxidant activity (EC50) revealed that pericarp extract had the highestα-amylase (0.46 mg/mL),α-glucosidase (0.37 mg/mL), and ACE (0.03 mg/mL) inhibitory activities while the seed extract had the least [α-amylase (0.76 mg/mL);α-glucosidase (0.73 mg/mL); and ACE (0.20 mg/mL)]. Furthermore, the extracts scavenged radicals, reduced Fe3+to Fe2+, and chelated Fe2+. The phenolic contents in the extracts ranged from 85.65 to 560.21 mg/100 g. The enzymes inhibitory and antioxidants potentials of the extracts could be attributed to their phenolic distributions which could be among the scientific basis for their use in the management of diabetes and hypertension. However, the pericarp appeared to be most promising.