Pharmacotherapy
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Many patients taking atypical antipsychotic drugs will experience weight gain. Evidence suggests that long-term treatment with these agents decreases glucose effectiveness, alters satiety signals, creates hormonal resistance to satiety control, and may have a direct effect on hypothalamic appetite centers. The serotonin(2c-) and histamine(1)-receptor antagonism of atypical antipsychotics may also lead to weight gain. ⋯ Although the study results do not provide clear substantial evidence that metformin, as an adjuvant to atypical antipsychotic use, will decrease weight gain and improve metabolic effects, they are encouraging. Additional studies of longer duration that include behavioral therapy and special diets should be conducted in patients from the United States. Currently, the drug is being used as a secondary or tertiary intervention, and its use may be considered in patients with a personal and/or family history of obesity or metabolic dysfunction, and in subjects who have rapid weight gain early in antipsychotic treatment.
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Comparative Study
Comparison of the Modification of Diet in Renal Disease and Cockcroft-Gault equations for dosing antimicrobials.
To determine the concordance between the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault equations for glomerular filtration rate (GFR) estimation, the impact of using each equation on antimicrobial dosing, the difference in estimated GFR in patients with acute kidney disease (AKD) versus chronic kidney disease (CKD), and the correlation between the MDRD, Cockcroft-Gault equation, and expert medical opinion for estimating GFR in patients with AKD. ⋯ The estimated GFR obtained with the MDRD equation was consistently higher than that from the Cockcroft-Gault equation in patients with AKD or CKD. In patients with AKD, the MDRD GFR more closely correlated with expert opinion than the Cockcroft-Gault, suggesting that the MDRD method may be applicable to this patient population. Moderate concordance between the two equations for the need for antimicrobial dosage adjustment due to renal dysfunction was found, but the specific dosage change was different for approximately 40% of patients, with 99% receiving higher doses when the MDRD GFR is used. These dosing differences may be significant, depending on drug safety profile, type of infection, and causative pathogen.
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To evaluate the effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on mortality in patients with severe sepsis. ⋯ The use of statins was associated with a protective effect in patients with severe sepsis, as demonstrated by a significant reduction in mortality compared with patients not receiving statins.
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Infectious diseases and impaired renal function often occur in critically ill patients, and delaying the start of appropriate empiric antimicrobial therapy or starting inappropriate therapy has been associated with poor outcomes. Our primary objective was to critically review and discuss the influence of chronic kidney disease (CKD) and acute kidney injury (AKI) on the clinical pharmacokinetic and pharmacodynamic properties of antimicrobial agents. The effect of continuous renal replacement therapies (CRRTs) and intermittent hemodialysis (IHD) on drug disposition in these two populations was also evaluated. ⋯ Forty antimicrobial, antifungal, and antiviral agents commonly used in critically ill patients were included for review. Dosage recommendations were synthesized from the 42 reviewed articles and peer-reviewed, evidence-based clinical drug databases to generate initial guidance for the determination of antimicrobial dosing strategies for critically ill adults. Because of the evolving process of critical illness, whether in patients with AKI or in those with CKD, prospective adaptation of these initial dosing recommendations to meet the needs of each individual patient will often rely on prospectively collected clinical and laboratory data.
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Injectable nicardipine is increasingly being used to manage neurovascular conditions. To better understand its place in therapy, we conducted an evidenced-based literature review. Two-hundred twenty-three article abstracts were identified; after independent review by two individuals and a supplemental manual search, 29 were deemed relevant and were included in this review. ⋯ Intraarterial nicardipine reduced angiographic diameter (p value not reported) and peak systolic velocities on transcranial Doppler images (p<0.001) in published case series. Given nicardipine's high cost relative to that of other agents and the limited evidence to support its use in patients with neurovascular conditions, this drug should be considered only in patients who have failed or have contraindications to alternative agents in the management of hypertension. Although intraarterial nicardipine appears to be promising in aneurysmal subarachnoid hemorrhage, well-designed studies are needed in this setting before its use can be routinely recommended.