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High impact drugs

Michael Medinger, Claudia Lengerke, Jakob Passweg
Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades...
2016: Leukemia Research Reports
Guillermo Blanco, Alexandra Junza, Dolores Barrón
Pharmaceuticals from veterinary treatments may enter terrestrial food webs when medicated livestock are available to wildlife in supplementary feeding stations aimed at the conservation of endangered scavengers. Here, we hypothesized that the exposure risk to livestock fluoroquinolones, as indicators of pharmaceutical burden in food, is related to the variable reliance of scavengers on domestic versus wild animal carcasses. Since the misuse of broad-spectrum antibiotics is a major predisposing factor for opportunistic mycoses, we evaluated disease signs potentially associated with diet-dependent drug exposure in nestlings of two threatened vultures...
October 14, 2016: Ecotoxicology and Environmental Safety
Mohamed M Abd El-Mawgod, Arwa S Alshaibany, Aeshah M Al-Anazi
BACKGROUND: Dysmenorrhea is one of the most common and important health problems, especially among young girls. It results in absence from school and work. It has some negative effects on the daily activities of patients. Because of cultural problems, patients ordinarily do not seek help from others in this situation. Identification of abnormal menstrual patterns during adolescence may permit early prevention of potential health concerns in adulthood. OBJECTIVES: The aim of this study was to determine the prevalence, severity, and impact of dysmenorrhea in secondary-school students and its association with school absenteeism in Arar city...
September 2016: Journal of the Egyptian Public Health Association
Santoshi Billakota, Saurabh R Sinha
INTRODUCTION: Continuous EEG (cEEG) monitoring is used in the intensive care unit (ICU) setting to detect seizures, especially nonconvulsive seizures and status epilepticus. The utility and impact of such monitoring in non-ICU patients are largely unknown. METHODS: Hospitalized patients who were not in an ICU and underwent cEEG monitoring in the first half of 2011 and 2014 were identified. Reason for admission, admitting service (neurologic and nonneurologic), indication for cEEG, comorbid conditions, duration of recording, EEG findings, whether an event/seizure was recorded, and impact of EEG findings on management were reviewed...
October 2016: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
Zachery R Reichert, Maha Hussain
The development of metastatic castration-resistant prostate cancer (mCRPC) signals the terminal disease phase. The preceding hormone-dependent disease setting is effectively managed with androgen deprivation therapy. This foundation of treatment has a high rate of biochemical and clinical response and meaningful clinical benefit but is finite in duration as most cancers will progress to castration resistance. Historically, treatment for mCRPC entailed androgen receptor (AR) inhibitors (nilutamide, flutamide, bicalutamide), nonspecific steroidal biosynthesis inhibitors (ketoconazole, itraconazole), steroids (prednisone, diethylstilbesterol, dexamethasone), or palliative chemotherapy (mitoxantrone, estramustine), but none of these strategies impacted survival...
September 2016: Cancer Journal
A Harrod, J Fulton, V T M Nguyen, M Periyasamy, L Ramos-Garcia, C-F Lai, G Metodieva, A de Giorgio, R L Williams, D B Santos, P J Gomez, M-L Lin, M V Metodiev, J Stebbing, L Castellano, L Magnani, R C Coombes, L Buluwela, S Ali
Drugs that inhibit estrogen receptor-α (ER) activity have been highly successful in treating and reducing breast cancer progression in ER-positive disease. However, resistance to these therapies presents a major clinical problem. Recent genetic studies have shown that mutations in the ER gene are found in >20% of tumours that progress on endocrine therapies. Remarkably, the great majority of these mutations localize to just a few amino acids within or near the critical helix 12 region of the ER hormone binding domain, where they are likely to be single allele mutations...
October 17, 2016: Oncogene
Mohamed Alalem, Alpana Ray, Bimal K Ray
Activation of mTOR is implicated in the development and progression of breast cancer. mTOR inhibition exhibited promising antitumor effects in breast cancer; however, its effect is compromised by several feedback mechanisms. One of such mechanisms is the upregulation of mTOR pathway in breast cancer cells. Despite the established role of mTOR activation in breast cancer, the status of total mTOR protein and its impact on the tumor behavior and response to treatment are poorly understood. Besides, the mechanisms underlying mTOR protein degradation in normal and cancer breast cells are still largely unknown...
October 17, 2016: Cancer Medicine
Matthew R Wilson, David S Jones, Gavin P Andrews
OBJECTIVES: This research examined the application of hot melt extrusion (HME) in the preparation of matrix formulations containing hydroxypropyl cellulose (HPC) as a base polymer in combination with methyl cellulose (MC) and hydroxypropyl methylcellulose (HPMC). METHODS: The limit to which formulations could control drug release under varying paddle speeds, high alcohol environments and high and low drug loads was investigated on a Caleva 10 ST dissolution tester...
October 17, 2016: Journal of Pharmacy and Pharmacology
Michael Clayton May, Paul Nielsen Andrews, Shadi Daher, Uday Nitin Reebye
BACKGROUND: Oral health care of patients with acquired immune deficiency syndrome (AIDS) due to human immunodeficiency virus (HIV) is a growing area of concern, taking into consideration the increased life expectancy of patients resulting from antiretroviral therapy. There is insufficient literature regarding the impact of dental implants in AIDS patients. This study investigated the long-term clinical outcome of implant placement in patients diagnosed with AIDS. METHODS: This monocentric study included AIDS patients with CD4 <200 cells/μL, age 18 years or older, and a minimum of one edentulous space requiring implant...
December 2016: Int J Implant Dent
Charles Béguelin, Darius Moradpour, Roland Sahli, Franziska Suter-Riniker, Alexander Lüthi, Matthias Cavassini, Huldrych F Günthard, Manuel Battegay, Enos Bernasconi, Patrick Schmid, Alexandra Calmy, Dominique Braun, Hansjakob Furrer, Andri Rauch, Gilles Wandeler
BACKGROUND AND AIMS: Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. We assessed the epidemiological characteristics of HDV infection in the nationwide Swiss HIV Cohort Study and evaluated its impact on clinical outcomes. METHODS: All HIV-infected patients with a positive HBsAg test were considered and tested for anti-HDV antibodies. HDV amplification and sequencing were performed in anti-HDV-positive patients...
October 13, 2016: Journal of Hepatology
Xinxin Li, Bryan Ruddy, Andrew Taberner
Hypodermic injections have been the standard for transcutaneous drug delivery for many years. However, needle phobia, pain, and risks of needle-stick injuries have manifested in poor patient compliance. Needle-free jet injections (NFJI) have been developed to address these drawbacks but the reliability of dose and depth of delivery have been limited by a lack of control over jet parameters, and by variability in the skin's mechanical properties among individuals. Moreover, the device size and cost have been restrained by the high pressure (>20MPa) required to penetrate the skin...
October 13, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ajit S Narang, Timothy Stevens, Mario Hubert, Srinivasa Paruchuri, Kevin Macias, Dilbir Bindra, Zhihui Gao, Sherif Badawy
Real-time process monitoring using a process analytical technology for granule size distribution can enable quality-by-design in drug product manufacturing. In this study, the resolution and sensitivity of chord length distribution (CLD) measured inline inside a high shear granulator using focused beam reflectance measurement (FBRM) C35 probe was investigated using different particle size grades of microcrystalline cellulose (MCC). In addition, the impact of water and impeller tip speed on the measurement accuracy as well as correlation with offline particle sizing techniques (FBRM, laser diffraction [Malvern Mastersizer(®)], microscopy [Sympatec QicPic(®)], and nested sieve analysis) was studied...
October 13, 2016: Journal of Pharmaceutical Sciences
Nicholas S Sigona, Jeffrey M Steele, Christopher D Miller
OBJECTIVES: To determine the impact of a pharmacist-driven beta-lactam allergy interview on antimicrobial therapy. SETTING: Tertiary care academic medical center. PRACTICE SETTING: Clarification of beta-lactam allergy may expand treatment options for patients and potentially improve outcomes, reduce toxicity, and reduce costs. PRACTICE INNOVATION: At our institution, a pilot service using a pharmacy resident and infectious diseases clinical pharmacist was implemented to clarify beta-lactam allergy information and, where appropriate, recommend a change to the patient's antibiotic therapy...
October 8, 2016: Journal of the American Pharmacists Association: JAPhA
X Jégouzo, M Desbordes, S Delègue, G Le Vacon, M Patrick, S Mouchabac
OBJECTIVES: Behavioral and psychological symptoms have a high prevalence in dementia. They include mood disorders, psychotic disorders and behavioral disorders such as aggression or screaming. Despite a number of side effects and an increased mortality, antipsychotic drugs are widely prescribed for treatment of this disorder. In France, this increased risk of mortality led in 2009 to the adoption of guidelines concerning all antipsychotics. The guidelines propose a sensible use of antipsychotics after the establishment of non-pharmacological measures...
October 12, 2016: L'Encéphale
Marivi Nabong Moen, Roar Fjær, El Hassan Hamdani, Jon K Laerdahl, Robin Johansen Menchini, Magnus Dehli Vigeland, Ying Sheng, Dag Erik Undlien, Bjørnar Hassel, Mustafa A Salih, Heba Y El Khashab, Kaja Kristine Selmer, Farrukh Abbas Chaudhry
Progressive myoclonus epilepsy is a heterogeneous group of disorders characterized by myoclonic and tonic-clonic seizures, ataxia and cognitive decline. We here present two affected brothers. At 9 months of age the elder brother developed ataxia and myoclonic jerks. In his second year he lost the ability to walk and talk, and he developed drug-resistant progressive myoclonus epilepsy. The cerebrospinal fluid level of glutamate was decreased while glutamine was increased. His younger brother manifested similar symptoms from 6 months of age...
October 14, 2016: Brain: a Journal of Neurology
F Salazar Meira, J Zemiacki, A E Figueiredo, L Viliano Kroth, D Saute Kochhann, D O d'Avila, M Traesel, D Saitovitch, C E Poli-de-Figueiredo
BACKGROUND: One of the main postoperative complications of kidney transplant is delayed graft function (DGF), which means absence of graft function after transplant or the need for dialysis during the first week post procedure. The occurrence of DGF currently in our hospital is high and has been attributed to a combination of many factors. The aim of this study was to evaluate the factors associated to DGF and their influence in the outcome of kidney transplants. METHODS: Historical cohort of 150 patients transplanted with live or deceased donor kidneys from 2011 to 2013...
September 2016: Transplantation Proceedings
Laura László, Balázs Sarkadi, Tamás Hegedűs
ABCG2/BCRP is a membrane protein, involved in xenobiotic and endobiotic transport in key pharmacological barriers and drug metabolizing organs, in the protection of stem cells, and in multidrug resistance of cancer. Pharmacogenetic studies implicated the role of ABCG2 in response to widely used medicines and anticancer agents, as well as in gout. Its Q141K variant exhibits decreased functional expression thus increased drug accumulation and decreased urate secretion. Still, there has been no reliable molecular model available for this protein, as the published structures of other ABC transporters could not be properly fitted to the ABCG2 topology and experimental data...
2016: PloS One
Argelia Rosillo -de la Torre, Luisa Rocha, Hermelinda Salgado-Ceballos, Perla E García Casillas, Gabriel Luna-Bárcenas
BACKGROUND: Pharmacoresistant epilepsy is a disabling neuronal disorder with harmful consequences that impact patient quality of life. Although psychiatric comorbidities are frequently present in patients with epilepsy, they are more common in those patients with pharmacoresistant epilepsy. Despite medical advances, the current existing therapeutic strategies for pharmacoresistant seizure control are not available for all patients and/or present disadvantages. Moreover, the conventional drug therapies for psychiatric comorbidities have several adverse effects...
October 13, 2016: Mini Reviews in Medicinal Chemistry
Saloumeh Kadkhodayan Fischer, Melissa Cheu, Kun Peng, John Lowe, James Araujo, Elaine Murray, Dana McClintock, John Matthews, Patricia Siguenza, An Song
Host cell proteins are manufacturing process-related impurities that may co-purify with the product despite extensive efforts to optimize the purification process. The risks associated with these impurities can vary and may be patient and/or therapeutic dependent. Therefore, it is critical to monitor and control the levels of these impurities in products and their potential impact on safety and efficacy. Lebrikizumab is a humanized immunoglobulin G4 monoclonal antibody (mAb) that binds specifically to soluble interleukin 13...
October 13, 2016: AAPS Journal
Dina Nair, Pooranaganga D Navneethapandian, Jaya Prasad Tripathy, Anthony D Harries, Joel S Klinton, Basilea Watson, Gomathi N Sivaramakrishnan, Devarajulu S Reddy, Lakshmi Murali, Mohan Natrajan, Soumya Swaminathan
BACKGROUND: India is replacing culture and drug sensitivity testing (CDST) with rapid molecular tests for diagnosing MDR-TB. We assessed the impact of rapid tests on time to initiation of treatment and outcomes in patients with MDR-TB compared with CDST. METHODS: A retrospective cohort study involving MDR-TB patients from six districts in Tamil Nadu state, who underwent CDST (2010-2011) and rapid tests (2012-2013). RESULTS: There were 135 patients in the CDST group and 389 in the rapid diagnostic test group...
October 13, 2016: Transactions of the Royal Society of Tropical Medicine and Hygiene
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