OBJECTIVES. This study examined the association of smoking status and pack-years of smoking with facial wrinkling in men and women. METHODS. We conducted a cross-sectional study of 299 never smokers, 551 former smokers and 286 current smokers, aged 30 through 69 years, drawn from a health maintenance organization. Smoking status, pack-years of smoking, and potential confounding variables were assessed by questionnaire. Facial wrinkle category, a dichotomous variable, and facial wrinkle score, a computed continuous variable, were assessed by blinded standardized visual assessment. Wrinkling was so uncommon among 30- through 39-year-old subjects that analyses were restricted to subjects aged 40 and over (227 never smokers, 456 former smokers, and 228 current smokers). RESULTS. With age, average sun exposure, and body mass index controlled, the estimated relative risk of moderate/severe wrinkling for current smokers compared to never smokers was 2.3 (95% confidence interval [CI] = 1.2, 4.2) among men and 3.1 (95% CI = 1.6, 5.9) among women. Pack-years was positively associated with facial wrinkle score in women aged 40 through 69 years and in men aged 40 through 59 years. In both groups, the increased risk of wrinkling was equivalent to about 1.4 years of aging. CONCLUSIONS. Our results support earlier findings that risk of facial wrinkling is greater in cigarette smokers than in never smokers.
Doses required to achieve desired vancomycin concentrations are similar in morbidly obese and normal weight patients when TBW is used as a dosing weight for the obese (approximately 30 mg x kg(-1) x d(-1)). Shorter dosage intervals may be needed when dosing morbidly obese patients so that steady-state trough concentrations remain above 5 microg x ml(-1) in this population. Because of the large amount of variation in required doses, vancomycin serum concentrations should be obtained in morbidly obese patients to ensure that adequate doses are being administered. Dosage requirements for morbidly obese patients with renal dysfunction require further study.
Ten healthy adults participated in a randomized, crossover drug interaction study testing procainamide only, procainamide plus levofloxacin, and procainamide plus ciprofloxacin. During levofloxacin therapy, most procainamide and N-acetylprocainamide (NAPA) pharmacokinetic parameters, including decreased renal clearances and renal clearance/creatinine clearance ratios, changed (P < 0.05). During ciprofloxacin treatment, only procainamide and NAPA renal clearances decreased significantly.Renal drug interactions in patients are often overlooked when new drug therapy is added to existing therapeutic regimens. Procainamide, N-acetylprocainamide (NAPA; the active metabolite of procainamide), and several fluoroquinolone antibiotics are eliminated renally by active tubular secretion (9,11,15,16,21). Procainamide serum concentrations increase and its pharmacokinetics change due to concurrent therapy with ofloxacin (15). The purpose of this study was to investigate the possibility of a renal drug interaction between procainamide and levofloxacin, one of the stereoisomers of ofloxacin. For comparison, the potential for a ciprofloxacin-procainamide drug interaction was also studied.(A portion of this work was presented in abstract form at the 2001 American College of Clinical Pharmacology Annual Meeting, Tampa, Fla.)Ten healthy adults (five males, five females; ages, 21 to 35 years; weights, 52 to 87 kg; seven Caucasians, three Asians) participated in the study. The investigation was approved by the university human subjects committee, and subjects provided written informed consent. All individuals had normal physical examinations, laboratory screening tests (serum electrolytes, renal and liver function tests, and complete blood cell counts), and 12-lead electrocardiograms. Subjects were within 20% of their ideal body weight, did not smoke tobacco-containing products, had no known allergy to study medications, took no additional medications, and, if female, had negative serum pregnancy tests (6). Beverages containing alcohol or methylxanthines were not allowed during the study period.The study was a three-way randomized, controlled trial designed to investigate a potential drug interaction between procainamide and two fluoroquinolone antibiotics. Subjects were not blinded from antibiotic study drugs because of obvious differences in dosage forms and administration schedules. Each of the following procedures was performed with procainamide alone (control phase) or on the fifth day of fluoroquinolone oral administration (500 mg of levofloxacin every day at 0800 h and 500 mg of ciprofloxacin every 12 h at 0800 h and 2000 h). Prior to admission to the Clinical Research Center for administration of procainamide, subjects were allowed to selfadminister the fluoroquinolone at home; compliance was assured by inspection of a medication administration diary, tablet counts of doses remaining in the pill vial, and subject interviews by investigators. In order for the study to proceed, all drug doses needed to be administered within 15 ...
and cefepime therapy in a murine peritonitis model. J Antimicrob Chemo-
The drugs used to treat cancer today are a confusing array of compounds with differing origins, mechanisms of action, antitumour spectra, and toxicities. There are 5 chemically distinct types of alkylating agents; the prototypical agent is chlormethine (mustine) and the most recent addition is ifosfamide. Generally these drugs all work in the same fashion and their activity is cell cycle proliferation-dependent but phase-nonspecific. The antimetabolites consist of methotrexate, the pyrimidine and purine analogues, and pentostatin, an adenosine deaminase inhibitor and relative newcomer to the class. The individual mechanisms of action of these agents differ but cytotoxicity is generally cell cycle phase-specific. Naturally occurring antineoplastic agents include the vinca alkaloids, the antitumour antibiotics, 1-asparaginase, the epipodophyllotoxins, and homoharringtonine; it is the most diverse collection of compounds. For these drugs as well as the antimetabolites, the therapeutic and toxic effects often depend heavily on duration of exposure to the drug, an effect known as schedule dependency. Finally, the agents that do not fit one of the above categories are cisplatin (cis-platinum II) and its analogue carboplatin (which is being actively investigated), hydroxycarbamide (hydroxyurea), procarbazine, hexamethylmelamine, amsacrine, and mitoxantrone (mitozantrone). In the future we can expect not only the emergence of new antineoplastic drugs, but also further refinements in the use of existing drugs. We are beginning to understand the various types of resistance manifested by tumour cells. Our ability to use these potent and highly toxic agents safely should continue to improve.
BackgroundWith the rise of antibiotic resistance, polymyxin use has re-emerged but with a concern of renal toxicity. This study aims to assess mortality, length of stay, and total hospitalization cost associated with acute kidney injury (AKI) among recipients of intravenous (IV) sodium colistimethate (CMS) or IV polymyxin B (PMB).MethodsWe conducted a retrospective database analysis using the Premier database from January 1, 2012, through September 30, 2015. Adults ≥18 years of age who were admitted for inpatient treatment with ≥3 consecutive days of CMS or PMB were included. Generalized linear models compared patients who developed AKI with those who did not. Models were adjusted for patient and clinical characteristics.ResultsA total of 4886 patients were included; 4103 patients received CMS, and 783 received PMB. In the multivariable analyses, the presence of AKI was associated with higher in-hospital mortality in both the CMS cohort (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.9–2.7; P < .001) and the PMB cohort (aOR, 2.7; 95% CI, 1.8–4.2; P < .001). In both cohorts, patients who developed AKI experienced longer hospital stays (9.7 days and 11.6 days in the CMS and PMB cohorts, respectively; P < .001). The mean total hospitalization costs for patients who developed AKI were $47 820 higher (95% CI, $34 918–$60 722) in the CMS cohort and $35 244 higher (95% CI, $17 561–$52 928) in the PMB cohort.ConclusionsThe clinical and economic burden of AKI in the context of polymyxin use is substantial. The use of effective antibiotics with limited toxicity should remain a priority.
Modifiable risk factors such as physical inactivity and smoking may place older women at risk for serious infections although the causal link is yet to be explained. Further research in this area may lead to new strategies aimed at reducing the serious burden of infections in the older population.
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