bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of ultrasound-guided prenatal diagnosis of prune belly syndrome in Papua New Guinea – implications for management
Authors: Ome Maria , Wangnapi Regina , Hamura Nancy , Umbers Alexandra J , Siba Peter , Laman Moses , Bolnga John , Rogerson Sheryle , Unger Holger W
Published: May 2013

Background

Prune belly syndrome is a rare congenital malformation of unknown aetiology and is characterised by abnormalities of the urinary tract, a deficiency of abdominal musculature and bilateral cryptorchidism in males. We report a case of prune belly syndrome from Papua New Guinea, which was suspected on pregnancy ultrasound scan and confirmed upon delivery.

Case presentation

A 26-year-old married woman, Gravida 3 Para 2, presented to antenatal clinic in Madang, Papua New Guinea, at 21+5weeks’ gestation by dates. She was well with no past medical or family history of note. She gave consent to participate in a clinical trial on prevention of malaria in pregnancy and underwent repeated ultrasound examinations which revealed a live fetus with persistent megacystis and anhydramnios. Both mother and clinicians agreed on conservative management of the congenital abnormality. The mother spontaneously delivered a male fetus weighing 2010 grams at 34 weeks’ gestation with grossly abnormal genitalia including cryptorchidism, penile aplasia and an absent urethral meatus, absent abdominal muscles and hypoplastic lungs. The infant passed away two hours after delivery. This report discusses the implications of prenatal detection of severe congenital abnormalities in PNG.

Conclusion

This first, formally reported, case of prune belly syndrome from a resource-limited setting in the Oceania region highlights the importance of identifying and documenting congenital abnormalities. Women undergoing antenatal ultrasound examinations must be carefully counseled on the purpose and the limitations of the scan. The increasing use of obstetric ultrasound in PNG will inevitably result in a rise in prenatal detection of congenital abnormalities. This will need to be met with adequate training, referral mechanisms and better knowledge of women’s attitudes and beliefs on birth defects and ultrasound. National medicolegal guidance regarding induced abortion and resuscitation of a fetus with severe congenital abnormalities may be required.
p-Hydroxycinnamic acid production directly from cellulose using endoglucanase- and tyrosine ammonia lyase-expressing Streptomyces lividans
Authors: Kawai Yoshifumi , Noda Shuhei , Ogino Chiaki , Takeshima Yasunobu , Okai Naoko , Tanaka Tsutomu , Kondo Akihiko
Published: May 2013

Background

p-Hydroxycinnamic acid (pHCA) is an aromatic compound that serves as a starting material for the production of many commercially valuable chemicals, such as fragrances and pharmaceuticals, and is also used in the synthesis of thermostable polymers. However, chemical synthesis of pHCA is both costly and harmful to the environment. Although pHCA production using microbes has been widely studied, there remains a need for more cost-effective methods, such as the use of biomass as a carbon source. In this study, we produced pHCA using tyrosine ammonia lyase-expressing Streptomyces lividans. In order to improve pHCA productivity from cellulose, we constructed a tyrosine ammonia lyase- and endoglucanase (EG)-expressing S. lividans transformant and used it to produce pHCA from cellulose.

Results

A Streptomyces lividans transformant was constructed to express tyrosine ammonia lyase derived from Rhodobacter sphaeroides (RsTAL). The transformant produced 786 or 736 mg/L of pHCA after 7 days of cultivation in medium containing 1% glucose or cellobiose as the carbon source, respectively. To enhance pHCA production from phosphoric acid swollen cellulose (PASC), we introduced the gene encoding EG into RsTAL-expressing S. lividans. After 7 days of cultivation, this transformant produced 753, 743, or 500 mg/L of pHCA from 1% glucose, cellobiose, or PASC, respectively.

Conclusions

RsTAL-expressing S. lividans can produce pHCA from glucose and cellobiose. Similarly, RsTAL- and EG-expressing S. lividans can produce pHCA from glucose and cellobiose with excess EG activity remaining in the supernatant. This transformant demonstrated improved pHCA production from cellulose. Further enhancements in the cellulose degradation capability of the transformant will be necessary in order to achieve further improvements in pHCA production from cellulose.
Volumetric three-dimensional intravascular ultrasound visualization using shape-based nonlinear interpolation
Authors: Rim Yonghoon , McPherson David D , Kim Hyunggun
Published: May 2013

Background

Intravascular ultrasound (IVUS) is a standard imaging modality for identification of plaque formation in the coronary and peripheral arteries. Volumetric three-dimensional (3D) IVUS visualization provides a powerful tool to overcome the limited comprehensive information of 2D IVUS in terms of complex spatial distribution of arterial morphology and acoustic backscatter information. Conventional 3D IVUS techniques provide sub-optimal visualization of arterial morphology or lack acoustic information concerning arterial structure due in part to low quality of image data and the use of pixel-based IVUS image reconstruction algorithms. In the present study, we describe a novel volumetric 3D IVUS reconstruction algorithm to utilize IVUS signal data and a shape-based nonlinear interpolation.

Methods

We developed an algorithm to convert a series of IVUS signal data into a fully volumetric 3D visualization. Intermediary slices between original 2D IVUS slices were generated utilizing the natural cubic spline interpolation to consider the nonlinearity of both vascular structure geometry and acoustic backscatter in the arterial wall. We evaluated differences in image quality between the conventional pixel-based interpolation and the shape-based nonlinear interpolation methods using both virtual vascular phantom data and in vivo IVUS data of a porcine femoral artery. Volumetric 3D IVUS images of the arterial segment reconstructed using the two interpolation methods were compared.

Results

In vitro validation and in vivo comparative studies with the conventional pixel-based interpolation method demonstrated more robustness of the shape-based nonlinear interpolation algorithm in determining intermediary 2D IVUS slices. Our shape-based nonlinear interpolation demonstrated improved volumetric 3D visualization of the in vivo arterial structure and more realistic acoustic backscatter distribution compared to the conventional pixel-based interpolation method.

Conclusions

This novel 3D IVUS visualization strategy has the potential to improve ultrasound imaging of vascular structure information, particularly atheroma determination. Improved volumetric 3D visualization with accurate acoustic backscatter information can help with ultrasound molecular imaging of atheroma component distribution.
Comparative proteome analysis of Tumor necrosis factor α-stimulated human Vascular Smooth Muscle Cells in response to melittin
Authors: Cho Hyun-Ji , Kang Jeong-Han , Park Kwan-Kyu , Choe Jung-Yoon , Park Yoon-Yub , Moon Yong-Suk , Chung Il-Kyung , Chang Hyeun-Wook , Kim Cheorl-Ho , Choi Yung Hyun , Kim Wun-Jae , Moon Sung-Kwon , Chang Young-Chae
Published: May 2013

Background

Bee venom has been used to relieve pain and to treat inflammatory diseases, including rheumatoid arthritis, in humans. To better understand the mechanisms of the anti-inflammatory and anti-atherosclerosis effect of bee venom, gel electrophoresis and mass spectrometry were used to identify proteins whose expression was altered in human Vascular Smooth Muscle Cells (hVSMCs) stimulated by tumor necrosis factor alpha after 12 h in the presence of melittin.

Results

To obtain valuable insights into the anti-inflammatory and anti-atherosclerosis mechanisms of melittin, two-dimensional (2-D) gel electrophoresis and MALDI-TOF/TOF were used. The proteome study, we showed 33 significant proteins that were differentially expressed in the cells treated with tumor necrosis factor alpha and melittin. Thirteen proteins were significantly increased in the cells treated with tumor necrosis factor alpha, and those proteins were reduced in the cells treated with melittin. Five of the proteins that showed increased expression in the cells treated with tumor necrosis factor alpha are involved in cell migration, including calreticulin, an essential factor of development that plays a role in transcription regulation. The proteins involved in cell migration were reduced in the melittin treated cells. The observed changes in the expression of GRP75, prohibitin, and a select group of other proteins were validated with reverse transcribed-PCR. It was confirmed that the observed change in the protein levels reflected a change in the genes level. In addition, the phosphorylation of EGFR and ERK was validated by analyzing the protein pathway.

Conclusion

Taken together, these data established that the expression of some proteins was significantly changed by melittin treatment in tumor necrosis factor alpha stimulated the cells and provided insights into the mechanism of the melittin function for its potential use as an anti-inflammatory agent.
Trends in parameterization, economics and host behaviour in influenza pandemic modelling: a review and reporting protocol
Authors: Carrasco Luis R , Jit Mark , Chen Mark I , Lee Vernon J , Milne George J , Cook Alex R
Published: May 2013

Background

The volume of influenza pandemic modelling studies has increased dramatically in the last decade. Many models incorporate now sophisticated parameterization and validation techniques, economic analyses and the behaviour of individuals.

Methods

We reviewed trends in these aspects in models for influenza pandemic preparedness that aimed to generate policy insights for epidemic management and were published from 2000 to September 2011, i.e. before and after the 2009 pandemic.

Results

We find that many influenza pandemics models rely on parameters from previous modelling studies, models are rarely validated using observed data and are seldom applied to low-income countries. Mechanisms for international data sharing would be necessary to facilitate a wider adoption of model validation. The variety of modelling decisions makes it difficult to compare and evaluate models systematically.

Conclusions

We propose a model Characteristics, Construction, Parameterization and Validation aspects protocol (CCPV protocol) to contribute to the systematisation of the reporting of models with an emphasis on the incorporation of economic aspects and host behaviour. Model reporting, as already exists in many other fields of modelling, would increase confidence in model results, and transparency in their assessment and comparison.
Diplotyper: diplotype-based association analysis
Authors: Kim Sunshin , Park KyungChae , Shin Chol , Cho Nam H , Ko Jeong-Jae , Koh InSong , Kwack KyuBum
Published: May 2013

Background

It was previously reported that an association analysis based on haplotype clusters increased power over single-locus tests, and that another association test based on diplotype trend regression analysis outperformed other, more common association approaches. We suggest a novel algorithm to combine haplotype cluster- and diplotype-based analyses.

Methods

Diplotyper combines a novel algorithm designed to cluster haplotypes of interest from a given set of haplotypes with two existing tools: Haploview, for analyses of linkage disequilibrium blocks and haplotypes, and PLINK, to generate all possible diplotypes from given genotypes of samples and calculate linear or logistic regression. In addition, procedures for generating all possible diplotypes from the haplotype clusters and transforming these diplotypes into PLINK formats were implemented.

Results

Diplotyper is a fully automated tool for performing association analysis based on diplotypes in a population. Diplotyper was tested through association analysis of hepatic lipase (LIPC) gene polymorphisms or diplotypes and levels of high-density lipoprotein (HDL) cholesterol.

Conclusions

Diplotyper is useful for identifying more precise and distinct signals over single-locus tests.
Altering physiological networks using drugs: steps towards personalized physiology
Authors: Grossman Adam D , Cohen Mitchell J , Manley Geoffrey T , Butte Atul J
Published: May 2013

Background

The rise of personalized medicine has reminded us that each patient must be treated as an individual. One factor in making treatment decisions is the physiological state of each patient, but definitions of relevant states and methods to visualize state-related physiologic changes are scarce. We constructed correlation networks from physiologic data to demonstrate changes associated with pressor use in the intensive care unit.

Methods

We collected 29 physiological variables at one-minute intervals from nineteen trauma patients in the intensive care unit of an academic hospital and grouped each minute of data as receiving or not receiving pressors. For each group we constructed Spearman correlation networks of pairs of physiologic variables. To visualize drug-associated changes we split the networks into three components: an unchanging network, a network of connections with changing correlation sign, and a network of connections only present in one group.

Results

Out of a possible 406 connections between the 29 physiological measures, 64, 39, and 48 were present in each of the three component networks. The static network confirms expected physiological relationships while the network of associations with changed correlation sign suggests putative changes due to the drugs. The network of associations present only with pressors suggests new relationships that could be worthy of study.

Conclusions

We demonstrated that visualizing physiological relationships using correlation networks provides insight into underlying physiologic states while also showing that many of these relationships change when the state is defined by the presence of drugs. This method applied to targeted experiments could change the way critical care patients are monitored and treated.
Association of anemia and renal function test among diabetes mellitus patients attending Fenote Selam Hospital, West Gojam, Northwest Ethiopia: a cross sectional study
Authors: Abate Alemayehu , Birhan Wubet , Alemu Abebe
Published: May 2013

Background

Anemia is a common problem in diabetic patients. Diabetic patients have a greater severity of anemia as the level of Glomerular Filtration Rate (GFR) decreases compared to non-diabetic patients. Despite these facts, anemia is unrecognized and largely untreated in patients with diabetes in Ethiopia particularly in those patients attending Fenote Selam Hospital. Therefore, this study was aimed to assess the association of anemia and renal function test among diabetes mellitus patients attending Fenote Selam Hospital, North West of Ethiopia.

Methods

An Institutional -based cross-sectional study was conducted from February 2012 to April 2012 on diabetes mellitus (DM) patients. Systematic random sampling technique was used to get the total sample size of 384 patients. A total of seven ml of venous blood was collected from diabetes mellitus patients; two ml was collected by EDTA anticoagualted vacutainer test tube for haemoglobin determination and 5 ml venous blood was collected by plain vacutainer tube for creatinine and Blood urea nitrogen determination. The data were double entered and analyzed using SPSS-16 statistical software. The degree of association between independent and dependent variables was assessed using bivariate and multivariate logistic regression analysis in terms of P-value and odds ratio with 95% confidence interval.

Results

Out of the total 384 DM patients included in the study 73 (19%) were anemic. Fifty three (13.8%), forty eight (12.5%), and two hundred eighty three (73.7%) DM patients had an estimated GFR <60 ml/min/1.73 m, 60 – 90 ml/min/ 1.73 m, and > 90 ml/min/1.73 m respectively. One hundred eleven (28.9%) diabetic patients had increased urine albumin level. There was a statistically significant association between anaemia and Glomerular filtration rate (P<0.05) with Odds ratio of 8.58 and CI (10.21, 49.94). As the glomerular filtration rate increase, the risk to be anemic will decrease dramatically.

Conclusion

The study showed that there was a significant association between anaemia and Glomerular filtration rate in DM patients. Therefore, DM patients should be strictly monitored for renal failure and anemia for proper management of diabetes patients.
Preclinical radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H
Authors: Bretin Florian , Warnock Geoffrey , Bahri Mohamed Ali , Aerts Joël , Mestdagh Nathalie , Buchanan Tim , Valade Anne , Mievis Frédéric , Giacomelli Fabrice , Lemaire Christian , Luxen André , Salmon Eric , Seret Alain , Plenevaux Alain
Published: May 2013

Background

[18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to evaluate the radiation dosimetry of [18F]UCB-H in a preclinical trial and to determine the maximum injectable dose according to guidelines for human biomedical research. The radiation dosimetry was derived by organ harvesting and dynamic micro positron emission tomography (PET) imaging in mice, and the results of both methods were compared.

Methods

Twenty-four male C57BL-6 mice were injected with 6.96 ± 0.81 MBq of [18F]UCB-H, and the biodistribution was determined by organ harvesting at 2, 5, 10, 30, 60, and 120 min (n = 4 for each time point). Dynamic microPET imaging was performed on five male C57BL-6 mice after the injection of 9.19 ± 3.40 MBq of [18F]UCB-H. A theoretical dynamic bladder model was applied to simulate urinary excretion. Human radiation dose estimates were derived from animal data using the International Commission on Radiological Protection 103 tissue weighting factors.

Results

Based on organ harvesting, the urinary bladder wall, liver and brain received the highest radiation dose with a resulting effective dose of 1.88E-02 mSv/MBq. Based on dynamic imaging an effective dose of 1.86E-02 mSv/MBq was calculated, with the urinary bladder wall and liver (brain was not in the imaging field of view) receiving the highest radiation.

Conclusions

This first preclinical dosimetry study of [18F]UCB-H showed that the tracer meets the standard criteria for radiation exposure in clinical studies. The dose-limiting organ based on US Food and Drug Administration (FDA) and European guidelines was the urinary bladder wall for FDA and the effective dose for Europe with a maximum injectable single dose of approximately 325 MBq was calculated. Although microPET imaging showed significant deviations from organ harvesting, the Pearson’s correlation coefficient between radiation dosimetry derived by either method was 0.9666.
Candida albicansescapes from mouse neutrophils
Authors: Ermert David , Niemiec Maria J , Röhm Marc , Glenthøj Andreas , Borregaard Niels , Urban Constantin F
Published: May 2013

Candida albicans, the most commonly isolated human fungal pathogen, is able to grow as budding yeasts or filamentous forms, such as hyphae. The ability to switch morphology has been attributed a crucial role for the pathogenesis of C. albicans. To mimic disseminated candidiasis in humans, the mouse is the most widely used model organism. Neutrophils are essential immune cells to prevent opportunistic mycoses. To explore potential differences between the rodent infection model and the human host, we compared the interactions of C. albicans with neutrophil granulocytes from mice and humans. We revealed that murine neutrophils exhibited a significantly lower ability to kill C. albicans than their human counterparts. Strikingly, C. albicans yeast cells formed germ tubes upon internalization by murine neutrophils, eventually rupturing the neutrophil membrane and thereby, killing the phagocyte. On the contrary, growth and subsequent escape of C. albicans are blocked inside human neutrophils. According to our findings, this blockage in human neutrophils might be a result of higher levels of MPO activity and the presence of α-defensins. We therefore outline differences in antifungal immune defense between humans and mouse strains, which facilitates a more accurate interpretation of in vivo results.
Use of β-Blockers, Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Risk of Breast Cancer Recurrence: A Danish Nationwide Prospective Cohort Study
Authors: Sørensen Gitte Vrelits , Ganz Patricia A. , Cole Steven W. , Pedersen Lars A. , Sørensen Henrik Toft , Cronin-Fenton Deirdre P. , Garne Jens Peter , Christiansen Peer M. , Lash Timothy L. , Ahern Thomas P.
Published: May 2013

Purpose

To estimate associations between use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs) and breast cancer recurrence in a large Danish cohort.

Patients and Methods

We enrolled 18,733 women diagnosed with nonmetastatic breast cancer between 1996 and 2003. Patient, treatment, and 10-year recurrence data were ascertained from the Danish Breast Cancer Cooperative Group registry. Prescription and medical histories were ascertained by linkage to the National Prescription Registry and Registry of Patients, respectively. β-Blocker exposure was defined in aggregate and according to solubility, receptor selectivity, and individual drugs. ACE inhibitor and ARB exposures were defined in aggregate. Recurrence associations were estimated with multivariable Cox regression models in which time-varying drug exposures were lagged by 1 year.

Results

Compared with never users, users of any β-blocker had a lower recurrence hazard in unadjusted models (unadjusted hazard ratio [HR] = 0.91; 95% CI, 0.81 to 1.0) and a slightly higher recurrence hazard in adjusted models (adjusted HR = 1.3; 95% CI, 1.1 to 1.5). Associations were similar for exposures defined by receptor selectivity and solubility. Although most individual β-blockers showed no association with recurrence, metoprolol and sotalol were associated with increased recurrence rates (adjusted metoprolol HR = 1.5, 95% CI, 1.2 to 1.8; adjusted sotalol HR = 2.0, 95% CI, 0.99 to 4.0). ACE inhibitors were associated with a slightly increased recurrence hazard, whereas ARBs were not associated with recurrence (adjusted ACE inhibitor HR = 1.2, 95% CI, 0.97 to 1.4; adjusted ARBs HR = 1.1, 95% CI, 0.85 to 1.3).

Conclusion

Our data do not support the hypothesis that β-blockers attenuate breast cancer recurrence risk.
Clinical Role of microRNAs in Cytogenetically Normal Acute Myeloid Leukemia: miR-155 Upregulation Independently Identifies High-Risk Patients
Authors: Marcucci Guido , Maharry Kati S. , Metzeler Klaus H. , Volinia Stefano , Wu Yue-Zhong , Mrózek Krzysztof , Nicolet Deedra , Kohlschmidt Jessica , Whitman Susan P. , Mendler Jason H. , Schwind Sebastian , Becker Heiko , Eisfeld Ann-Kathrin , Carroll Andrew J. , Powell Bayard L. , Kolitz Jonathan E. , Garzon Ramiro , Caligiuri Michael A. , Stone Richard M. , Bloomfield Clara D.
Published: May 2013

Purpose

To evaluate the impact of miR-155 on the outcome of adults with cytogenetically normal (CN) acute myeloid leukemia (AML) in the context of other clinical and molecular prognosticators and to gain insight into the leukemogenic role of this microRNA.

Patients and Methods

We evaluated 363 patients with primary CN-AML. miR-155 levels were measured in pretreatment marrow and blood by NanoString nCounter assays that quantified the expression of the encoding gene MIR155HG. All molecular prognosticators were assessed centrally. miR-155–associated gene and microRNA expression profiles were derived using microarrays.

Results

Considering all patients, high miR-155 expression was associated with a lower complete remission (CR) rate (P < .001) and shorter disease-free survival (P = .001) and overall survival (OS; P < .001) after adjusting for age. In multivariable analyses, high miR-155 expression remained an independent predictor for a lower CR rate (P = .007) and shorter OS (P < .001). High miR-155 expressers had approximately 50% reduction in the odds of achieving CR and 60% increase in the risk of death compared with low miR-155 expressers. Although high miR-155 expression was not associated with a distinct microRNA expression profile, it was associated with a gene expression profile enriched for genes involved in cellular mechanisms deregulated in AML (eg, apoptosis, nuclear factor-κB activation, and inflammation), thereby supporting a pivotal and unique role of this microRNA in myeloid leukemogenesis.

Conclusion

miR-155 expression levels are associated with clinical outcome independently of other strong clinical and molecular predictors. The availability of emerging compounds with antagonistic activity to microRNAs in the clinic provides the opportunity for future therapeutic targeting of miR-155 in AML.
Multicenter Phase II Study of Bendamustine Plus Rituximab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Ohmachi Ken , Niitsu Nozomi , Uchida Toshiki , Kim Seok Jin , Ando Kiyoshi , Takahashi Naoki , Takahashi Naoto , Uike Naokuni , Eom Hyeon Seok , Chae Yee Soo , Terauchi Takashi , Tateishi Ukihide , Tatsumi Mitsuaki , Kim Won Seog , Tobinai Kensei , Suh Cheolwon , Ogura Michinori
Published: May 2013

Purpose

Effective and less aggressive therapies are required for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for or have undergone autologous stem-cell transplantation (ASCT). The present phase II study assessed the efficacy and safety of bendamustine plus rituximab (BR) in this population.

Patients and Methods

Patients with relapsed or refractory DLBCL treated with one to three prior chemotherapy regimens received rituximab 375 mg/m2intravenous (IV) infusion on day 1 and bendamustine 120 mg/m2by IV infusion on days 2 and 3 of each 21-day cycle for up to six cycles. The primary end point was overall response rate (ORR), and the secondary end points were complete response (CR) rate, progression-free survival (PFS), and safety.

Results

Sixty-three patients were enrolled, and 59 received BR. The median age was 67 years (range, 36 to 75 years), and 62.7% of patients were 65 years of age or older. Fifty-seven patients (96.6%) were previously treated with rituximab-containing chemotherapy. The ORR was 62.7% (95% CI, 49.1% to 75.0%), with a CR rate of 37.3% (95% CI, 25.0% to 50.9%). The ORRs were comparable between patients ≥ 65 years of age and less than 65 years (62.2% and 63.6%, respectively). The median PFS was 6.7 months (95% CI, 3.6 to 13.7 months). The most frequently observed grade 3 or 4 adverse events were hematologic: lymphopenia (78.0%), neutropenia (76.3%), leukopenia (72.9%), CD4 lymphopenia (66.1%), and thrombocytopenia (22.0%).

Conclusion

BR is a promising salvage regimen for patients with relapsed or refractory DLBCL after rituximab-containing chemotherapy, warranting further investigation.
Dynamic Scheduling of a Two-Server Parallel Server System with Complete Resource Pooling and Reneging in Heavy Traffic: Asymptotic Optimality of a Two-Threshold Policy
Authors: Ghamami Samim , Ward Amy R.
Published: May 2013

We consider a dynamic control problem for a parallel server system commonly known as the N-system. An N-system is a two-server parallel server system with two job classes, one server that can serve both classes, and one server that can only serve one class. We assume that jobs within each class arrive according to a renewal process. The random service time of a job has a general distribution that may depend on both the job's class and the server providing the service. Each job independently reneges, or abandons the queue without receiving service, if service does not begin within an exponentially distributed amount of time. The objective is to minimize the expected infinite horizon discounted cost of holding jobs in the system and having customers abandon, by dynamically scheduling waiting jobs to available servers.

It is not possible to solve this control problem exactly, and so, we consider an asymptotic regime in which the system satisfies both a heavy traffic and a resource pooling condition. Then, we solve the limiting Brownian control problem, and interpret its solution as a policy in the original N-system. We label the servers and job classes so that server 1 can only serve class 1 and server 2 can serve both classes. The policy we propose has two thresholds. There is one threshold on the total number of jobs in the system, and one threshold on the number of class 1 jobs in the system. These thresholds are used to determine which job class server 2 should serve. We show that this proposed policy is asymptotically optimal within a specified class of admissible policies in the heavy traffic limit, and has the same limiting cost as the Brownian control problem solution.
Appendicitis in a Spigelian hernia: an unusual cause for a tender right iliac fossa mass
Authors: Thomas MP , Avula SK , England R , Stevenson L
Published: May 2013

Spigelian hernias are a rare type of hernia through the Spigelian aponeurosis, whose contents commonly include omentum or small bowel. In the absence of incarceration or strangulation, they can be difficult to diagnose clinically. In the emergency setting, they can present rarely as a painful abdominal mass and computed tomography provides a reliable diagnostic imaging modality. We report an emergency presentation of a Spigelian hernia containing the appendix.
A concealed small bowel perforation in an adult secondary to bicycle handlebar trauma
Authors: Ghosh SC , Nolan GJ , Simpson RR
Published: May 2013

Traumatic abdominal wall hernia (TAWH) secondary to bicycle handlebar is a rare injury. The majority of the literature describes abdominal wall herniation in children. We present a rare case of TAWH in an adult with a concealed small bowel perforation. Although clinical examination in conjunction with computed tomography can exclude the majority of solid organ injuries, small bowel injuries can often be missed. Our case initially revealed a serosal tear in the small bowel but, on close inspection, a separate 3mm perforation was identified, hidden in the small bowel mesentery. We strongly support a low threshold for operative intervention if there is any suspicion. Moreover, we stress the importance of meticulous examination during laparotomy as this injury could have been easily missed, resulting in potential morbidity or mortality in a patient sustaining such an injury.
Transanal haemorrhoidal dearterialisation with mucopexy versus stapler haemorrhoidopexy: a randomised trial with long-term follow-up
Authors: Lucarelli R , Picchio M , Caporossi M , De Angelis F , Di Filippo A , Stipa F , Spaziani E
Published: May 2013

Introduction

The present study aimed to compare the long-term results of transanal haemorrhoidal dearterialisation (THD) with mucopexy and stapler haemorrhoidopexy (SH) in treatment of grade III and IV haemorrhoids.

Methods

One hundred and twenty-four patients with grade III and IV haemorrhoids were randomised to receive THD with mucopexy (n=63) or SH (n=61). A telephone interview with a structured questionnaire was performed at a median follow-up of 42 months. The primary outcome was the occurrence of recurrent prolapse. Patients, investigators and those assessing the outcomes were blinded to group assignment.

Results

Recurrence was present in 21 patients (16.9%). It occurred in 16 (25.4%) in the THD group and 5 (8.2%) in the SH group (p=0.021). A second surgical procedure was performed in eight patients (6.4%). Reoperation was open haemorrhoidectomy in seven cases and SH in one case. Five patients out of six in the THD group and both patients in the SH group requiring repeat surgery presented with grade IV haemorrhoids. No significant difference was found between the two groups with respect to symptom control. Patient satisfaction for the procedure was 73.0% after THD and 85.2% after SH (p=0.705). Postoperative pain, return to normal activities and complications were similar.

Conclusions

The recurrence rate after THD with mucopexy is significantly higher than after SH at long-term follow-up although results are similar with respect to symptom control and patient satisfaction. A definite risk of repeat surgery is present when both procedures are performed, especially for grade IV haemorrhoids.
Complications following hemiarthroplasty for displaced intracapsular femoral neck fractures in the absence of routine follow-up
Authors: Chaplin VK , Matharu GS , Knebel RWC
Published: May 2013

Introduction

Hemiarthroplasty is the most commonly performed surgery for displaced intracapsular femoral neck fractures. At present, it is not routine practice to follow up these patients despite the risk of all the complications associated with arthroplasty. This study aimed to determine the prevalence and nature of complications occurring following hemiarthroplasty that re-presented to this centre in the absence of routine postoperative follow-up.

Methods

Consecutive patients undergoing uncemented hip hemiarthroplasty for displaced intracapsular femoral neck fractures at a district general hospital between 2004 and 2009 were identified. Data were collected from the hospital database on all complications relating to the index procedure, further surgery performed and mortality.

Results

There were 490 hemiarthroplasties performed in 477 patients (mean age: 80 years, 75% female). Of these, 110 (22%) were referred postoperatively for specialist orthopaedic review. The prevalence of any complication following hemiarthroplasty was 12% (n=59) and the prevalence of hemiarthroplasty failure was 8% (n=40). The most common indications for failure were periprosthetic fracture (28%), aseptic femoral loosening (25%) and unexplained pain (25%). Persistent hip pain and poor mobility accounted for most complications not requiring further surgery (n=15). The mortality rate within 30 days and 1 year of hemiarthroplasty was 6% (n=31) and 29% (n=146) respectively.

Conclusions

In the absence of routine follow-up, complications were encountered frequently in patients undergoing hip hemiarthroplasty, with most requiring further surgery. Appropriate services should be implemented to allow timely referral for orthopaedic assessment, and enable the early identification and treatment of postoperative complications.
Factors affecting the healing of the perineum following surgery
Authors: Ip B , Jones M , Bassett P , Phillips R
Published: May 2013

Introduction

The aim of this study was to establish patient and procedural factors associated with the development of an unhealed perineum in patients undergoing a proctectomy or excision of an ileoanal pouch.

Methods

A review of 194 case notes for procedures performed between 1997 and 2009 was carried out. All patients had at least 12 months’ follow-up. Univariate and multivariate analyses were performed in 16 parameters. For those patients who developed an unhealed perineum, Cox regression analysis was performed to establish healing over a 12-month period.

Results

Two hundred patients were included in the study, of which six had unknown wound status and were subsequently excluded. This left 194 study patients. Of these, 86 (44%) achieved primary wound healing with a fully healed perineum and 108 (56%) experienced primary wound failure. With reference to the latter, 63 (58%) healed by 12 months. Comparing patients with an initially intact perineum with those with initial wound failure showed pre-existing sepsis was highly relevant (odds ratio: 4.32, 95% confidence interval [CI]: 2.16–8.62, p<0.001). In patients who had an unhealed perineum initially, perineal sepsis and surgical treatment were both significantly associated with time to healing (hazard ratio [HR]: 0.54, 95% CI: 0.31–0.93, p=0.03; and HR: 0.42, 95% CI: 0.21–0.84, p=0.01).

Conclusions

The presence of pre-existing perineal sepsis is associated with an unhealed perineum following proctectomy in inflammatory bowel disease (IBD) and non-IBD surgery. Further studies are indicated to establish perineal sepsis as a causative factor.
Topical steroids for chronic wounds displaying abnormal inflammation
Authors: Bosanquet DC , Rangaraj A , Richards AJ , Riddell A , Saravolac VM , Harding KG
Published: May 2013

Introduction

Chronic, non-healing wounds are often characterised by an excessive, and detrimental, inflammatory response. We review our experience of using a combined topical steroid, antibiotic and antifungal preparation in the treatment of chronic wounds displaying abnormal and excessive inflammation.

Methods

A retrospective review was undertaken of all patients being treated with a topical preparation containing a steroid (clobetasone butyrate 0.05%), antibiotic and antifungal at a tertiary wound healing centre over a ten-year period. Patients were selected as the primary treating physician felt the wounds were displaying excessive inflammation. Healing rates were calculated for before and during this treatment period for each patient. Changes in symptom burden (pain, odour and exudate levels) following topical application were also calculated.

Results

Overall, 34 ulcers were identified from 25 individual patients (mean age: 65 years, range: 37–97 years) and 331 clinic visits were analysed, spanning a total time of 14,670 days (7,721 days ‘before treatment’ time, 6,949 days ‘during treatment’ time). Following treatment, 24 ulcers demonstrated faster rates of healing, 3 ulcers showed no significant change in healing rates and 7 were healing more slowly (p=0.0006). Treatment generally reduced the burden of pain and exudate, without affecting odour.

Conclusions

In normal wound healing, inflammation represents a transient but essential phase of tissue repair. In selected cases, direct application of a steroid containing agent has been shown to improve healing rates, presumably by curtailing this phase. Further evaluation is required to establish the role of preparations containing topical steroids without antimicrobials in the management of chronic wounds.
Should Clear Care Be Kept behind the Ambulatory Care Pharmacy Counter?; Similarity between Two Forms of Solu-Medrol; Over-the-Counter Eye Drops May be Harmful If Swallowed; Nuedexta-Neulasta Mix-ups
Authors: Cohen Michael R. , Smetzer Judy L.
Published: May 2013

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers’ names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters’ wishes as to the level of detail included in publications.
New Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: More Choices Bring More Challenges
Authors: Howard Patricia A.
Published: May 2013

For patients with atrial fibrillation, anticoagulant therapy is essential to reduce the risk of ischemic stroke that is associated with this arrhythmia. Historically, warfarin has been the preferred treatment for patients at moderate to high risk despite many potential limitations. With the development of newer oral anticoagulants, clinicians now have 3 additional options: dabigatran, rivaroxaban, and apixaban. Although these agents clearly offer some advantages over warfarin, they may not be appropriate for all patients. This article will discuss factors that should be considered when selecting among these various anticoagulants.
Drug Monographs: Cabozantanib and Omacetaxine
Authors: Solimando Dominic A. , Ho Kristin V. , Waddell J. Aubrey
Published: May 2013

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
Can the Targeted Use of a Discharge Pharmacist Significantly Decrease 30-Day Readmissions?
Authors: Pal Aroop , Babbott Stewart , Wilkinson Samaneh Tavalali
Published: May 2013

Background

The prevalence and cost of hospital readmissions have gained attention. The ability to identify patients at high risk for hospital readmission has implications for quality and costs of care. Medication errors have been shown to increase the risk for readmission.

Objective

To study the impact of a pharmacist-based predischarge medication reconciliation and counseling program on 30-day readmission rates and determine whether polypharmacy and problem medications are important screening criteria.

Methods

A prospective, nonrandomized cohort study performed at a single medical-surgical unit with telemetry capability at a single academic medical center. The participants were 729 patients, aged 18 years and older, who were discharged between July 1 and October 29, 2010. The intervention was pharmacist medication reconciliation and counseling based on a screening tool. The primary outcome was 30-day readmission rate. Secondary outcomes were the presence of polypharmacy and problem medications and their relationship with observed 30-day readmission rate, including calculation of a problem med/polypharmacy score.

Results

The pharmacy review group (n = 537) had a lower 30-day readmission rate than the group receiving usual care (n = 192) (16.8% vs 26.0%; odds ratio [OR] 0.572; 95% CI, 0.387-0.852; P = .006). Polypharmacy, defined as either 5 or more or 10 or more scheduled medications, alone and in combination with at least one problem medication had higher 30-day readmission rates. A score of no factors present exhibited good negative predictive value.

Conclusions

Medication reconciliation and counseling by a pharmacist reduced the 30-day readmission rate. Polypharmacy and problem medications appear to have value individually and together. A pharmacist, guided by a screening tool in predischarge medication reconciliation, is one option to effectively reduce 30-day readmissions.
High-Risk Non-ST Elevation Acute Coronary Syndrome Outcomes in Patients Treated with Unfractionated Heparin Monitored Using Anti-Xa Concentrations versus Activated Partial Thromboplastin Time
Authors: Hamilton Leslie A. , Abbott Gregory V. , Cooper Julie B.
Published: May 2013

Background

While the activated partial thromboplastin time (aPTT) is the most widely used assay to monitor unfractionated heparin (UFH), providing a general measure of the extent of anticoagulation, it does not reliably correlate with the blood concentration of heparin or its antithrombotic effect. While cost and availability have limited the widespread use of UFH in hospitals, monitoring UFH with heparin levels has been shown to reduce both the number of monitoring tests and the time to a therapeutic range.

Objectives

To compare outcomes in patients with non-ST elevation acute coronary syndrome (ACS) treated with weight-based UFH monitored with anti-Xa concentrations versus aPTT.

Methods

A retrospective chart review was completed in patients admitted with high-risk ACS and compared to the UFH arm of the SYNERGY trial. The primary outcome included the clinical endpoint of all-cause death or non-fatal myocardial infarction until time of hospital discharge. Safety endpoints evaluated included incidence of stroke and major bleeding.

Results

The primary endpoint occurred in 6.3% of patients in the study cohort compared to 6.5% of patients in the heparin arm of the SYNERGY trial at 48 hours ( P = .006). Bleeding was reduced in the study cohort with a significant decrease in GUSTO severe bleeding ( P = .007). Additionally the study cohort had significantly fewer patients with an absolute drop in hemoglobin or hematocrit. Thrombolysis in Myocardial Infarction (TIMI) major and minor bleeding, rate of transfusion, and platelet counts were similar between groups.

Conclusions

Outcomes for high-risk ACS patients receiving heparin monitored by anti-Xa concentrations are noninferior to heparin monitored by aPTT.
Review of Insulin Therapy and Pen Use in Hospitalized Patients
Authors: Davis Estella M. , Foral Pamela A. , Dull Ryan B. , Smith April N.
Published: May 2013

Objective

Hyperglycemia is common among hospitalized patients, affecting approximately 40% of patients at the time of hospital admission, despite the fact that 1 in every 8 patients has no previous diagnosis of diabetes. Hyperglycemia has been associated with poor patient outcomes, including higher rates of morbidity and mortality across a range of conditions. This review discusses options for the effective management of hyperglycemia with a focus on the use of disposable insulin pens in the hospital.

Methods

Literature, including guidelines for hospital management of hyperglycemia, and information regarding methods of insulin administration were reviewed

Results

Appropriate glucose control via administration of insulin within hospitals has been acknowledged as an important goal and is consistent with achieving patient safety. Insulin may be administered subcutaneously using a pen or vial and syringe or infused intravenously. Levels of patient and provider satisfaction are higher with pen administration than with vial and syringe. Insulin pens have many safety and convenience features including enhanced dose accuracy and autocover/autoshield pen needles.

Conclusion

Use of insulin pens instead of vials and syringes can provide several advantages for hospitalized patients, including greater satisfaction among them and health care providers, improved safety, and reduced costs. These advantages can continue following patient discharge.
An Optimistic but Cautionary Outlook on Mobile Health
Authors: Fox Brent I. , Felkey Bill G.
Published: May 2013

Mobile health (mHealth) pushes forward and provides an active area for research. We briefly review 2 mHealth research articles and discuss the implications of their findings for hospital pharmacists.