Association Between Ward-Specific Antimicrobial Use Density and Methicillin-Resistant Staphylococcu Aureus Surveillance: A 60-Month Study.

Association between ward-specific antimicrobial use density and methicillin-resistant Staphylococcu aureus surveillance: a 60-month study.

Infect Drug Resist. 2013; 6: 59-66
Yoshida J, Kikuchi T, Matsubara N, Asano I, Ogami N

It is not known whether or not ward-specific antimicrobial use density (AUD) affects the ratio of methicillin-resistant Staphylococcus aureus (MRSA) in culture-positive S. aureus. A 60-month study was attempted to ascertain the association between inpatient MRSA ratio and ward-specific AUDs as well as the former and latter study intervals, specimen types, and ward specialty. During the study, the professionals in infection control regulated the use of broad-spectrum antimicrobials and those for MRSA. By both month and ward, the ratio of inpatients positive for MRSA to those positive for S. aureus was calculated. Factors associated with MRSA ratio included AUDs averaged for the sampling month and its previous month, outpatient MRSA ratio by age, ward specialty, specimen type, and half intervals to represent historical changes. Of a total of 4,245 strains of S. aureus isolated during the 5-year study, 2,232 strains (52.6%) were MRSA. By year, outpatient MRSA ratio at age ?15 decreased in later years, as did inpatient MRSA ratio. Multivariate analysis for inpatient MRSA ratio revealed a positive risk in AUDs for meropenem (odds ratio [OR] 1.761; 95% confidence interval [CI] 1.761-2.637, P = 0.01), imipenem-cilastatin (OR 1.583; 95% CI 1.087-2.306, P = 0.02), ampicillin-sulbactam (OR 1.623; 95% CI 1.114-2.365, P = 0.01), and minocycline (OR 1.680; CI 1.135-2.487, P = 0.01), respiratory care ward (OR 2.292; 95% CI 1.085-4.841, P = 0.03), and outpatient MRSA ratio (OR 1.536; 95% CI 1.070-2.206, P = 0.02). Use of broad-spectrum antimicrobials, such as meropenem, imipenem-cilastatin, and ampicillin-sulbactam may increase inpatient MRSA ratio. Ward factor should be included in MRSA surveillance because of the possible effect on AUD and considering patients’ backgrounds. HubMed – drug

Gamma secretase inhibitors of Notch signaling.

Onco Targets Ther. 2013; 6: 943-55
Olsauskas-Kuprys R, Zlobin A, Osipo C

The numerous processes involved in the etiology of breast cancer such as cell survival, metabolism, proliferation, differentiation, and angiogenesis are currently being elucidated. However, underlying mechanisms that drive breast cancer progression and drug resistance are still poorly understood. As we discuss here in detail, the Notch signaling pathway is an important regulatory component of normal breast development, cell fate of normal breast stem cells, and proliferation and survival of breast cancer initiating cells. Notch exerts a wide range of critical effects through a canonical pathway where it is expressed as a type I membrane precursor heterodimer followed by at least two subsequent cleavages induced by ligand engagement to ultimately release an intracellular form to function as a transcriptional activator. Notch and its ligands are overexpressed in breast cancer, and one method of effectively blocking Notch activity is preventing its cleavage at the cell surface with ?-secretase inhibitors. In the context of Notch signaling, the application of clinically relevant anti-Notch drugs in treatment regimens may contribute to novel therapeutic interventions and promote more effective clinical response in women with breast cancer. HubMed – drug

Comparative pharmacokinetic and pharmacodynamic evaluation of branded and generic formulations of meloxicam in healthy male volunteers.

Ther Clin Risk Manag. 2013; 9: 303-11
Tacca MD, Pasqualetti G, Gori G, Pepe P, Di Paolo A, Lastella M, De Negri F, Blandizzi C

The primary aim of the present study was to assess the pharmacokinetic bioequivalence between a generic formulation of meloxicam 15 mg tablets (Meloxicam Hexal) and its respective brand product (Mobic), in order to verify whether the generic product conforms to the regulatory standards of bioequivalence in the postmarketing setting. As a secondary exploratory aim, the pharmacodynamic effects of the two formulations were also evaluated by means of rating scales following hyperalgesia induced by cutaneous freeze injury.A single 15 mg dose of generic or branded meloxicam tablets was administered to 24 healthy male volunteers in a crossover fashion. Plasma samples, collected for 24 hours after dosing, were assayed for meloxicam concentration by a validated highperformance liquid chromatography method.THE ANALYSIS OF PHARMACOKINETIC PARAMETERS DID NOT SHOW ANY SIGNIFICANT DIFFERENCE BETWEEN THE TWO MELOXICAM FORMULATIONS: the 90% confidence intervals fell within the acceptance range of 80%-125% (0.84-1.16 for area under the curve [0-24], and 0.89-1.23 for peak concentration). No difference in the pharmacodynamic end point was observed between the two groups.The pharmacokinetic profiles of the two meloxicam formulations confirm the regulatory criteria for bioequivalence; pharmacodynamic data indicate a similar antihyperalgesic effect. The two formulations can be used interchangeably in the clinical setting. HubMed – drug

Update on optimal use of lisdexamfetamine in the treatment of ADHD.

Neuropsychiatr Dis Treat. 2013; 9: 977-83
Madaan V, Kolli V, Bestha DP, Shah MJ

Lisdexamfetamine (LDX) has been a recent addition to the treatment armamentarium for Attention Deficit Hyperactivity Disorder (ADHD). It is unique among stimulants as it is a prodrug, and has been found to be safe and well-tolerated medication in children older than 6 years, adolescents and adults. It has a smooth onset of action, exerts its action up to 13 hours and may have less rebound symptoms. LDX has proven to be effective in the treatment of ADHD in placebo controlled trials, and improved performance in simulated academic and work environments have been noticed. Both stimulant-naïve and stimulant-exposed patients with ADHD appear to benefit from LDX. It has also shown some promise in improving emotional expression and executive function of patients with ADHD. Adverse effects such as decrease in sleep, loss of appetite and others have been reported with LDX use, just as with other stimulant formulations. Since most such studies exclude subjects with preexisting cardiac morbidity, prescribing precautions should be taken with LDX in such subjects, as with any other stimulant. Study subjects on LDX have been reported to have low scores on drug likability scales, even with intravenous use; as a result, LDX may have somewhat less potential for abuse and diversion. There is a need for future studies comparing other long acting stimulants with LDX in ADHD; in fact clinical trials comparing LDX with OROS (osmotic controlled-release oral delivery system) methylphenidate are currently underway. Furthermore, the utility of this medication in other psychiatric disorders and beyond ADHD is being investigated. HubMed – drug

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