bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topical Aminophylline: Is it Safe and Effective in Causing Regional Fat Loss?
Authors: Tong Lisa M , Gericke Kristin R 
Published: July 2017

Objective: To provide a better understanding of the efficacy and possible adverse effects of topical aminophylline in causing regional fat loss. Data Source: Pertinent English-language literature (1958–1995). Study Selection: Representative articles documenting mechanisms of action and types of drug-induced reactions, as well as treatment options. Data Extraction: Data were extracted only from articles that documented relevant and substantive information backed by clinical studies. Data Synthesis: Topical aminophylline 2% thigh cream has been introduced as a method of treating cellulite, or dimpled thighs and buttocks. The proposed method of action is by increasing local concentration, thereby stimulating lipolysis. Data from two small clinical trials showed that the cream reduced thigh girth and had no known adverse effects. However, adverse dermatologic effects caused by aminophylline have been reported in the past. Conclusions: Topical aminophylline cream appears to be a reasonable option for regional reduction of thigh girth for some people and has not shown any adverse effects. Nevertheless, larger, long-term studies need to be done.
Terfenadine-Induced Torsade de Pointes: Risk Factors and Mechanisms
Authors: Chan Thomas Yk 
Published: July 2017

Objective: To review the risk factors and mechanisms of terfenadine-induced torsade de pointes and to discuss how this adverse reaction might be avoided. Data Sources: Previous reports of terfenadine-induced torsade de pointes and studies of the underlying mechanisms were identified by a MEDLINE search or from the reference lists of pertinent articles. Study Selection and Data Extraction: All relevant articles were included in the review. Pertinent information was selected for discussion. Data Synthesis: Terfenadine is extensively (99%) metabolized by CYP3A4 to an active acid metabolite (terfenadine carboxylate), and with therapeutic dosages, unchanged terfenadine is usually undetectable in plasma. A review of all the reported cases of torsade de pointes indicated that most patients had one or more factors that would be expected to cause excessively high concentrations of unchanged terfenadine, such as overdose; use of supratherapeutic dosages; concurrent use of CYP3A4 inhibitors such as ketoconazole, itraconazole, erythromycin, and troleandomycin; and liver dysfunction. Many patients had one or more factors known to predispose to drug-induced torsade de pointes (e.g., preexisting prolonged QT interval, ischemic heart disease, hypokalemia). Pharmacokinetic studies in healthy volunteers have shown that ketoconazole, itraconazole, erythromycin, and clarithromycin can alter the metabolism of terfenadine and result in the accumulation of unchanged terfenadine, which is associated with significant prolongation of the QT interval. In vitro studies have shown that the proarrhythmic effects of terfenadine are secondary to the blockade of cardiac potassium channels. Terfenadine carboxylate does not have such an effect. Conclusions: Supratherapeutic dosages of terfenadine should never be used. The concurrent use of CYP3A4 inhibitors should be avoided. Terfenadine should be avoided in patients with liver dysfunction or factors known to predispose to drug-induced torsade de pointes.
Pharmacy Technician Competencies for Practice in an Oncology Pharmacy
Authors: Waddell J Aubrey , Hannan Lance C , Stephens Marissa R 
Published: July 2017

Objective: To document the additional competencies that a well-trained pharmacy technician, with no previous oncology pharmacy training or experience, needs to practice effectively in an oncology pharmacy; and to develop a form to document the training of oncology pharmacy technicians at our institution. Design: From September 1, 1997, to November 1, 1997, the oncology pharmacist and the oncology pharmacy technicians developed a list of pharmacy technician competencies that were believed to be unique to pharmacy technician practice in an oncology pharmacy. Information from MEDLINE searches, drug manufacturer materials, and reference books was used to support the competencies identified. Setting: This project was conducted at Brooke Army Medical Center, a 450-bed teaching and research institution of the US Army Medical Department. Results: Twenty-five oncology pharmacy technician competencies were documented. This list was made into a form for inclusion in each oncology pharmacy technician's competency-based assessment folder and for use in training of future oncology pharmacy technicians. Conclusions: There are a significant number of additional competencies that a well-trained pharmacy technician needs in order to practice effectively in our institution's oncology pharmacy. The identification of these additional competencies facilitated the development of a form to document the training of oncology pharmacy technicians.
Comparison of Dissolution between Regular-Release and Halves of Extended-Release Methylphenidate Tablets
Authors: Erramouspe John , Jarvi Eric J 
Published: July 2017

Objective: To compare the in vitro dissolution of methylphenidate hydrochloride from regular-release tablets to halves of extended-release tablets. Design: Regular-release 10-mg methylphenidate tablets and halves of 20-mg extended-release tablets from two manufacturers (MD Pharmaceuticals, Inc., and Ciba Pharmaceutical Company) were dissolved according to the USP method specified for regular-release methylphenidate tablets. Samples were collected at 0.25, 0.5, 0.75, 1, 2, 3, 3.5, 4, 5, 6, and 7 hours. Methylphenidate concentration was determined by HPLC. Results: Regular-release methylphenidate tablets had statistically greater cumulative dissolution at all sample collection times of 2 hours or less compared with halves of extended-release tablets. The most dramatic difference occurred in the first 30 minutes, at which time the difference in cumulative dissolution was 63% (generic) and 55% (Ritalin). At 3 hours and thereafter, there was no significant difference in cumulative dissolution. Conclusions: Despite being cut in half, extended-release methylphenidate still does not dissolve as fast as regular-release tablets. Halving methylphenidate extended-release tablets may be a clinically acceptable means of achieving a prolonged-acting 10-mg dose.
Worsening Hepatic Encephalopathy Secondary to Zolpidem
Authors: Clark Adam 
Published: July 2017

Objective: To report a case of worsening hepatic encephalopathy secondary to ingestion of Zolpidem. Case Summary: A 41-year-old white man had postoperative complications 11 months after liver transplantation. Complications included narrowing of the choledochal anastomosis site, cyclosporine nephrotoxicity, and recurrent hepatitis C. Approximately seven months after transplantation, the patient experienced elevations in liver enzyme concentrations, lethargy, ascites, fever, chills, and nausea. Examination of a biopsy sample revealed recurrent hepatitis C. The patient's condition did not resolve despite administration of interferon alfa-2b, and his mental status began to deteriorate secondary to hepatic encephalopathy. One day before admission, the patient was given Zolpidem 5 mg for sleep; one hour after taking Zolpidem, he awoke in a stupor and was not oriented to place or time. When he became increasingly incoherent and verbally abusive, family members brought him to the emergency department. Although the patient exhibited mental status deterioration before receiving Zolpidem, considering the strong temporal relationship, his rapidly worsening state may be attributable to the drug. The patient subsequently required a second liver transplant in addition to a kidney transplant as a result of cyclosporine nephrotoxicity. The patient was not rechallenged with Zolpidem nor given flumazenil. Discussion: One pathophysiologic explanation for hepatic encephalopathy implicates endogenously produced benzodiazepine agonists. In patients with portal-systemic shunting, psychoactive compounds escape metabolism and are subsequently free to cross the blood-brain barrier. This mechanism is supported by reports of successful treatment of patients who have encephalopathy with flumazenil, a benzodiazepine antagonist. Hence, it follows that a benzodiazepine agonist could potentially exacerbate encephalopathic symptomatology. Zolpidem, although structurally unrelated to benzodiazepines, is a benzodiazepine agonist that binds preferentially to the benzodiazepine1 ω1 subtype of the γ-aminobutyric acid (GABAA) receptor complex. Therefore, administration of Zolpidem to patients with encephalopathy may worsen the condition by contributing to the accumulation of benzodiazepine agonists within the central nervous system. Conclusions: Although this patient's worsening mental status could be explained by a naturally evolving encephalopathic state, it is possible that Zolpidem exacerbated his decline. Existing evidence supports this view. First, an endogenously produced, benzodiazepine-related mechanism of hepatic encephalopathy is described in the literature. Second, benzodiazepine-like substances have been detected in the serum of patients with encephalopathy who have not received benzodiazepine therapy. Finally, clinical evidence supports the use of flumazenil in encephalopathic patients. Thus, it is likely that administration of Zolpidem hastened the mental decline of this patient.
Neuroleptic Malignant Syndrome Spectrum: A Case Report
Authors: Alao Adekola O , Yolles Jennifer C , Armenta Wendy , Michaels Anne T 
Published: July 2017

Objective: To report a suspected case of subclinical neuroleptic malignant syndrome (NMS) that possibly responded to electroconvulsive therapy. Case Summary: A 51-year-old white woman with a history of schizoaffective disorder, depressed type, was admitted to our inpatient unit after presenting with all features of NMS except fever. The patient's symptoms were markedly improved after eight courses of electroconvulsive therapy. Discussion: The “spectrum concept” of NMS is increasingly being recognized. More controlled studies are required to understand the components of this syndrome.
Evaluation of Losartan Usage in a Regional Hospital in Hong Kong
Authors: Chang Sophie , Tam Beverly H , Tse Blouie PY , Chan Grace MC , Lee Benjamin SC , Raymond Kenneth , Critchley Julian AJH , Chan Juliana CN 
Published: July 2017

Objective: To determine whether losartan usage follows the hospital's guidelines in terms of indications and reasons for use and to assess the accuracy of physicians in completing the losartan usage monitoring forms. Design: Drug utilization survey. Setting: A major government hospital in Hong Kong. Participants: Inpatients or outpatients prescribed losartan for the first time. Intervention: Physicians were to complete a monitoring form with both indications and reasons for losartan use. Main Outcome Measures: The appropriateness of losartan prescribing was evaluated in terms of indications (for hypertension with impaired left-ventricular function or hypertension in diabetic patients with persistent proteinuria) and reasons for preferred use (previous intolerance to adverse effects of angiotensin-converting enzyme inhibitors). The accuracy of completed monitoring forms was also assessed. Results: Forty-eight patients were prescribed losartan since its addition to the hospital formulary through the end of the study period (September 1997-May 1998). A review of medical records (regardless of the information provided by the physicians on the monitoring forms) revealed that 39 patients (81.3%) were prescribed losartan for appropriate indications and that 22 (45.8%) were given losartan rather than angiotensin-converting enzyme inhibitors for appropriate reasons according to the guidelines. Both appropriate indications and reasons were met in only 15 patients (31.3%). Of the 48 monitoring forms that were collected, three (6.3%) were not completed. The concordance rate of information provided by the doctors and information from case notes was 61.5% for indications and 34.8% for reasons of preferred use. Conclusions: Adherence to the hospital's usage guidelines and accuracy of the monitoring forms were suboptimal. Considering the high cost of losartan and its potential for long-term use, more educational activities, better dissemination of information, and more frequent evaluation of the acceptability of recommended usage guidelines are warranted.
Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma
Authors: Paludo Jonas , Mikhael Joseph R. , LaPlant Betsy R. , Halvorson Alese E. , Kumar Shaji , Gertz Morie A. , Hayman Suzanne R. , Buadi Francis K. , Dispenzieri Angela , Lust John A. , Kapoor Prashant , Leung Nelson , Russell Stephen J. , Dingli David , Go Ronald S. , Lin Yi , Gonsalves Wilson I. , Fonseca Rafael , Bergsagel P. Leif , Roy Vivek , Sher Taimur , Chanan-Khan Asher A. , Ailawadhi Sikander , Stewart A. Keith , Reeder Craig B. , Richardson Paul G. , Rajkumar S. Vincent , Lacy Martha Q. 
Published: July 2017

Key Points
PVD is an active combination in relapsed lenalidomide-refractory MM patients. PVD with weekly bortezomib offers a simpler, more convenient, and well-tolerated regimen option.
Maternal intake of sugar during pregnancy and childhood respiratory and atopic outcomes
Authors: Bédard Annabelle , Northstone Kate , Henderson A. John , Shaheen Seif O. 
Published: July 2017

The possible role of maternal consumption of free sugar during pregnancy in the inception of respiratory and atopic diseases has not been studied. We aimed to study the relationship between maternal intake of free sugar during pregnancy and respiratory and atopic outcomes in the offspring in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children.We analysed associations between maternal intake of free sugar in pregnancy (estimated by a food frequency questionnaire), and current doctor-diagnosed asthma, wheezing, hay fever, eczema, atopy, serum total IgE and lung function in children aged 7–9 years (n=8956 with information on maternal diet in pregnancy and at least one outcome of interest).After controlling for potential confounders, maternal intake of free sugar was positively associated with atopy (OR for highestversuslowest quintile of sugar intake 1.38, 95% CI 1.06–1.78; per quintile p-trend=0.006) and atopic asthma (OR 2.01, 95% CI 1.23–3.29; per quintile p-trend=0.004). These associations were not confounded by intake of sugar in early childhood, which was unrelated to these outcomes.Our results suggest that a higher maternal intake of free sugar during pregnancy is associated with an increased risk of atopy and atopic asthma in the offspring, independently of sugar intake in early childhood.
A novel immune biomarkerIFI27discriminates between influenza and bacteria in patients with suspected respiratory infection
Authors: Tang Benjamin M. , Shojaei Maryam , Parnell Grant P. , Huang Stephen , Nalos Marek , Teoh Sally , O'Connor Kate , Schibeci Stephen , Phu Amy L. , Kumar Anand , Ho John , Meyers Adrienne F. A. , Keynan Yoav , Ball Terry , Pisipati Amarnath , Kumar Aseem , Moore Elizabeth , Eisen Damon , Lai Kevin , Gillett Mark , Geffers Robert , Luo Hao , Gul Fahad , Schreiber Jens , Riedel Sandra , Booth David , McLean Anthony , Schughart Klaus 
Published: July 2017

Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals within vitroexperiments using well-established infection models.We identified a single-gene biomarker,IFI27, which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers.In vitrostudies showed thatIFI27was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria.In vivostudies confirmed thatIFI27was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions),IFI27displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections.IFI27represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting; its implementation may improve the diagnosis and management of respiratory infection.
A longitudinal modelling study estimates acute symptoms of community acquired pneumonia recover to baseline by 10 days
Authors: Wootton Daniel G. , Dickinson Laura , Pertinez Henry , Court Joanne , Eneje Odiri , Keogan Lynne , Macfarlane Laura , Wilks Sarah , Gallagher Jane , Woodhead Mark , Gordon Stephen B. , Diggle Peter J. 
Published: July 2017

Our aims were to address three fundamental questions relating to the symptoms of community-acquired pneumonia (CAP): Do patients completely recover from pneumonia symptoms? How long does this recovery take? Which factors influence symptomatic recovery?We prospectively recruited patients at two hospitals in Liverpool, UK, into a longitudinal, observational cohort study and modelled symptom recovery from CAP. We excluded patients with cancer, immunosuppression or advanced dementia, and those who were intubated or palliated from admission. We derived a statistical model to describe symptom patterns.We recruited 169 (52% male) adults. Multivariable analysis demonstrated that the time taken to recover to baseline was determined by the initial severity of symptoms. Severity of symptoms was associated with comorbidity and was inversely related to age. The pattern of symptom recovery was exponential and most patients’ symptoms returned to baseline by 10 days.These results will inform the advice given to patients regarding the resolution of their symptoms. The recovery model described here will facilitate the use of symptom recovery as an outcome measure in future clinical trials.
Chronic pulmonary aspergillosis complicating sarcoidosis
Authors: Uzunhan Yurdagül , Nunes Hilario , Jeny Florence , Lacroix Maxime , Brun Sophie , Brillet Pierre-Yves , Martinod Emmanuel , Carette Marie-France , Bouvry Diane , Charlier Caroline , Lanternier Fanny , Planès Carole , Tazi Abdellatif , Lortholary Olivier , Baughman Robert P. , Valeyre Dominique 
Published: July 2017

Chronic pulmonary aspergillosis (CPA) complicating sarcoidosis (SA) is associated with high mortality, and there is a lack of clarity regarding the relative contributions of SA or CPA.This was a retrospective single-centre study on CPA-SA.In total, 65 patients (44 men), aged 41.4±13.5 and 48.3±11.9 years at the time of SA and CPA diagnoses, respectively, were included between 1980 and 2015. Of these, 64 had fibrocystic SA, most often advanced, with composite physiological index (CPI) >40 (65% of patients) and pulmonary hypertension (PH) (31%), and 41 patients (63%) were treated for SA (corticosteroids or immunosuppressive drugs). Chronic cavitary pulmonary aspergillosis (CCPA) was the most frequent CPA pattern. Regarding treatment, 55 patients required long-term antifungals, 14 interventional radiology, 11 resection surgery and two transplantation. Nearly half of the patients (27; 41.5%) died (mean age 55.8 years); 73% of the patients achieved 5-year survival and 61% 10-year survival. Death most often resulted from advanced SA and rarely from haemoptysis. CPI, fibrosis extent and PH predicted survival. Comparison with paired healthy controls without CPA did not show any difference in survival, but a higher percentage of patients had high-risk mould exposure.CPA occurs in advanced pulmonary SA. CPA-SA is associated with high mortality due to the underlying advanced SA rather than to the CPA. CPI, fibrosis extent and PH best predict outcome.
Complete genome sequence of Microbulbifer sp. CCB-MM1, a halophile isolated from Matang Mangrove Forest, Malaysia
Authors: Moh Tsu Horng , Lau Nyok-Sean , Furusawa Go , Amirul Al-Ashraf Abdullah 
Published: July 2017

Abstract
Microbulbifer sp. CCB-MM1 is a halophile isolated from estuarine sediment of Matang Mangrove Forest, Malaysia. Based on 16S rRNA gene sequence analysis, strain CCB-MM1 is a potentially new species of genus Microbulbifer. Here we describe its features and present its complete genome sequence with annotation. The genome sequence is 3.86 Mb in size with GC content of 58.85%, harbouring 3313 protein coding genes and 92 RNA genes. A total of 71 genes associated with carbohydrate active enzymes were found using dbCAN. Ectoine biosynthetic genes, ectABC operon and ask_ect were detected using antiSMASH 3.0. Cell shape determination genes, mreBCD operon, rodA and rodZ were annotated, congruent with the rod-coccus cell cycle of the strain CCB-MM1. In addition, putative mreBCD operon regulatory gene, bolA was detected, which might be associated with the regulation of rod-coccus cell cycle observed from the strain.
Regionalization and Outcomes of Lung Cancer Surgery in Ontario, Canada
Authors: Bendzsak Anna M. , Baxter Nancy N. , Darling Gail E. , Austin Peter C. , Urbach David R. 
Published: July 2017

Purpose Regionalization of complex surgery to high-volume hospitals has been advocated based on cross-sectional volume-outcome studies. In April 2007, the agency overseeing cancer care in Ontario, Canada, implemented a policy to regionalize lung cancer surgery at 14 designated hospitals, enforced by economic incentives and penalties. We studied the effects of implementation of this policy. Methods Using administrative health data, we used interrupted time series models to analyze the immediate and delayed effects of implementation of the policy on the distribution of lung cancer surgery among hospitals, surgical outcomes, and health services use. Results From 2004 to 2012, 16,641 patients underwent surgery for lung cancer. The proportion of operations performed in designated hospitals increased from 71% to 89% after the policy was implemented. Although operative mortality decreased from 4.1% to 2.9% (adjusted odds ratio, 0.68; 95% CI, 0.58 to 0.81; P < .001), the reduction was due to a preexisting declining trend in mortality. In contrast, in the years after implementation of the policy, length of hospital stay decreased more than expected from the baseline trend by 7% per year (95% CI, 5% to 9%; P < .001), and the distance traveled by all patients to the hospital for surgery increased by 4% per year (95% CI, 0% to 8%; P = .03), neither of which were explained by preexisting trends. Analyses limited to patients ≥ 70 years of age demonstrated a reduction in operative mortality (odds ratio, 0.80 per year after regionalization; 95% CI, 0.67 to 0.95; P = .01). Conclusion A policy to regionalize lung cancer surgery in Ontario led to increased centralization of surgery services but was not independently associated with improvements in operative mortality. Improvements in length of stay and in operative mortality among elderly patients suggest areas where regionalization may be beneficial.