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We investigated the comparative efficacy and safety of dirithromycin and erythromycin in the treatment of skin and soft tissue infections in this double-blind, randomized, multicentre study, in which 439 patients were randomized to treatment with dirithromycin (500 mg daily for 5 days) or erythromycin (250 mg every 6 h for 7 days). All randomized patients were included in the termination analysis, which showed that 187 of 220 (85.0%) dirithromycin recipients and 177 of 219 (80.8%) erythromycin recipients were clinically cured or improved (95% confidence interval (CI) −3.0% to +11.4%). In the termination analysis of the 211 bacteriologically evaluable patients, clinical cure or improvement occurred in 83 of 100 (83%) dirithromycin recipients and in 89 of 111 (80.2%) erythromycin recipients (95% CI −7.8% to +13.4%), and bacteriological eradication occurred in 85 of 100 (85%) and 89 of 111 (80.2%), respectively. Adverse events were similar in incidence and nature between the two groups, except that there was less nausea with dirithromycin (3.6% versus 8.2%; P = 0.042). Ten of 220 (4.5%) dirithromycin recipients and 27 of 219 (12.3%) erythromycin recipients returned >20% of their prescribed medication (P = 0.033). In the treatment of skin and soft tissue infections, dirithromycin (500 mg daily for 5 days) was comparable in efficacy to, and caused significantly less nausea than, erythromycin (250 mg every 6 h for 7 days). Compliance with the dirithromycin regimen was superior to that with the erythromycin regimen. [ABSTRACT FROM PUBLISHER]

The coefficient of diffusion of air through the pore water of clay soils has been measured directly and has been shown to be markedly less than for free water and to decrease with water content. It has been shown that these low coefficients of diffusion are not accounted for by the sinuosity of the flow channels, or by any important departure from Henry's law of solution at curved air-water interfaces. The main factors appear to be constrictions in the flow channels and the reduced viscosity of the adsorbed water. It is concluded that air-water equilibrium in partly saturated soils will be attained much more slowly than is generally assumed. [ABSTRACT FROM AUTHOR]

Preventing bovine respiratory disease (BRD) among incoming calves is a challenge for feedlot or backgrounding systems. The objective of this study was to determine the effect of Excede® at arrival or at revaccination on morbidity, mortality, and gain in both feedlot and pasture receiving systems. A total of 2,264 steer calves from 3 buyers were assigned randomly to pens receiving one of three treatments with 12 replications per treatment. Seven reps were in a feedlot receiving system (20 steers/pen; 36 m2/steer) and 5 reps were on cool-season pastures (88-152 steers/1.6-10.1 ha pasture). All calves received modified-live viral vaccine and Haemophilus somnus bacterin at initial processing and reprocessing. All calves received injectable anthelmintic at initial processing and 7-way Clostridium spp. bacterin-toxoid at reprocessing (median 18 d; d 16-27). Treatments included no antibiotic at arrival (CON), Excede (6.6 mg/kg BW) at arrival (ARR), or Excede (6.6 mg/kg BW) at revaccination (REVAC). Respiratory disease incidence and BW data were analyzed accounting for correlated observations of steer within pen. No differences (P < 0.05) of initial or final BW, or ADG were observed due to treatment. Initial BW, treatment, receiving system (pasture or feedlot), and buyer explained the cumulative incidence of respiratory disease for the study period (P < 0.01) in a generalized estimating equations logistic regression model. Cumulative incidence of BRD was 4.7 ± 1.1%, 11.0 ± 1.9%, and 13.8 ± 2.1% for ARR, CON, and REVAC, respectively. The ARR model-adjusted incidence of BRD was less than CON (P < 0.01). The model-adjusted incidence of BRD among REVAC steers was not significantly different from CON. Cumulative incidence of BRD was less (P = 0.02) for pasture receiving than feedlot receiving, 7.4 ± 1.1% and 11.0 ± 2.1% respectively. Most incidents of BRD occurred during the first 14 days of arrival and before the REVAC medication was administered. The ARR medication effectively improved animal health status by reducing BRD incidence. [ABSTRACT FROM AUTHOR]

Discusses the abstract of the study 'Evaluation of initial implants on performance and carcass quality in feedlot heifers,' presented at the American Society of Animal Science's Midwestern Branch conference on March 17-19, 2003, in Des Moines, Iowa.

With consistently rising rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) since 2014, the need for increased screening, testing, and treatment of bacterial sexually transmitted infections (STIs) in people at risk is clear. In this study, people with HIV were asked to complete a comprehensive audio computer-assisted self-interview sexual history at routine clinic-based laboratory visits every 3-6 months. The sexual health screening resulted in an automated summary of recommended bacterial STI tests. Self-collection of recommended extragenital CT/GC specimens was implemented to decrease the need for a provider to collect the specimen(s) and to give more control to the client. In total, extragenital CT/GC testing returned a 7.3% ( n  = 11) test positivity for CT and/or GC, with the highest test positivity of 14% ( n  = 7) among rectal swabs and 4% ( n  = 4) for pharyngeal swabs. Urogenital testing for combined CT/GC returned a 4.8% ( n  = 11) test positivity. All participants with extragenital CT/GC who underwent simultaneous urine testing returned discordant laboratory results, with urine collected at the same clinic visit resulting as negative. In addition, 7 of 11 (63.6%) of the positive extragenital GC/CT cases were asymptomatic. Therefore, extragenital site-specific testing was essential in appropriately diagnosing and treating CT and GC among participants. When extragenital STI testing was recommended, participants needing extragenital CT/GC specimens primarily chose self-collection after a brief demonstration. Error rates between self- versus provider-collected samples did not differ, and participants provided positive feedback on the intervention and self-collection process in satisfaction surveys taken at the end of each visit.

Geographic access to community pharmacies is an important aspect of access to appropriate medicines. This study aimed to explore changes in the number and location of pharmacies in New Zealand and determine whether some populations have poor geographical access to pharmacies. Pharmacy numbers in New Zealand have been declining since the mid-1980s, and, adjusted for population growth, there are now only half the number there was in 1965. While the urbanisation of pharmacies has been matched by loss of population in rural areas, the loss of pharmacies from smaller rural towns leaves many people with poor access to pharmacy services., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: To assess the dose-response relationship, efficacy and safety of tabalumab, a human monoclonal antibody that neutralises membrane-bound and soluble B-cell activating factor (BAFF), in patients with rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX)., Methods: In this phase 2, 24-week, double-blind, placebo-controlled, dose-ranging study, patients with RA (N=158) on stable  MTX were randomised by Bayesian-adaptive method to receive 1, 3, 10, 30, 60, or 120 mg tabalumab or placebo subcutaneously every 4 weeks for 24 weeks. The primary objective was to test for a significant dose-response relationship using a statistical model of the proportion of patients having ≥50% improvement in American College of Rheumatology (ACR) criteria (ACR50) at week 24 (prespecified α=0.10)., Results: At week 24, a significant dose-response relationship was observed using ACR50 (p=0.059) and ACR20 (p=0.044) response rates. Using model-estimated data, only 120 mg had significantly higher ACR50 and ACR20 response rates versus placebo (p<0.05). Observed response rates were significantly higher for 120 mg versus placebo as measured by ACR50 at weeks 12 (p=0.039) and 20 (p=0.018), but not week 24, and by ACR20 at weeks 12 (p=0.011) and 24 (p=0.039). Mean DAS28 C-reactive protein  improved with 120 mg at week 24 (p=0.048). Frequency of TEAEs was similar across groups (range 50-69%, p=0.884). Ten (8.2%) tabalumab and 5 (13.9%) placebo patients reported a serious adverse event (SAE). Infections occurred more frequently in patients exposed to tabalumab (30.3% vs 19.4%). Serious infections were reported in 3 (2.5%) tabalumab-treated patients only., Conclusions: A dose-response relationship was detected with monthly subcutaneous tabalumab. A significant effect was detected with the 120 mg dose with no unexpected safety signals. CLINICAL TRIAL #: NCT00785928.

Purpose: Pharmacy dispensing databases provide a comprehensive source of data on medicines use free from many of the biases inherent in administrative databases. There are challenges associated with using pharmacy databases however. This paper describes the methods we used, and their performance, so that other researchers considering using pharmacy databases may benefit from our experiences., Methods: Data were collected from all nine pharmacy dispensing databases in an isolated New Zealand town for the period October 2005-September 2006. Probabilistic record matching was used to link individuals across pharmacies. Patient addresses from the pharmacy data were geo-located to small areas so an area measure of socioeconomic deprivation could be assigned. Medicines were coded according to the ATC-DDD drug classification system., Results: Data on 619,264 dispensings were collected. Record matching reduced an initial pool of individuals from 54,484 to 38,027. Socioeconomic deprivation ranks were assigned for 30,972 (93%) of the 33,375 unique addresses identified, or 36,048 (95%) of individuals. ATC codes were assigned to 613,490 (99%) of the dispensings, with DDDs assigned to 561,223 (91%). Overall, 93% of dispensing records had complete demographic and drug information., Conclusions: The methods described in this paper generated a rich dataset for medicines use research. These methods, while initially resource-intensive, can to a great extent be automated and applied to other locations, and will hopefully prove useful to other researchers facing similar challenges with using pharmacy databases. However, it is difficult to envisage these methods being viable on a long-term or national scale., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Terfenadine is metabolized by the cytochrome P-450 3A subfamily of enzymes (CYP3A). Certain macrolide antibiotic agents inhibit CYP3A and, when coadministered with terfenadine, result in a drug interaction. The authors compared the abilities of dirithromycin (a new macrolide antibiotic agent), its major metabolite erythromycylamine, and the known CYP3A substrate terfenadine to inhibit CYP3A in vitro. The hydroxylation of midazolam in human liver microsomes was used as a probe for CYP3A activity. Dirithromycin and erythromycylamine were low affinity inhibitors of CYP3A (inhibitory binding affinities of 493 mumol/L and 701 mumol/L, respectively); conversely, terfenadine was a moderate affinity inhibitor (inhibitory binding affinity of 28 mumol/L). Based on these data, the authors tested the hypothesis that dirithromycin would not interact with terfenadine in humans. Six healthy men received terfenadine alone (60 mg twice daily) for 8 days, after which dirithromycin (500 mg once daily) was added to the terfenadine regimen for an additional 10 days. The pharmacokinetics of terfenadine (and its acid metabolite) and the QTc interval were measured during both treatments, and it was found that neither parameter was affected. In this study, dirithromycin was found to have low affinity for human CYP3A in vitro, which is in accordance with the study's finding that in vivo dirithromycin has no major effect on the metabolism of the CYP3A substrate terfenadine in humans.

Dirithromycin is a new macrolide antibiotic that is effective against group A beta-hemolytic streptococcal pharyngotonsillitis. This prospective, multicenter, randomized study compared the serum and tonsil tissue concentrations of erythromycylamine (to which dirithromycin is rapidly converted by nonenzymatic hydrolysis during absorption) and erythromycin after 5- and 10-day regimens of dirithromycin and erythromycin, respectively. Thirty-nine patients undergoing elective tonsillectomy but without active tonsillitis were assigned in randomized fashion to receive dirithromycin 500 mg orally once daily (n = 22) or erythromycin base 250 mg orally four times daily (n = 17). Data from 12 patients receiving dirithromycin and 10 receiving erythromycin were eligible for analysis. Mean serum concentrations (+/-standard deviation) of erythromycylamine and erythromycin were 0.20 +/- 0.07 microgram/mL and 0.12 +/- 0.25 microgram/mL, respectively, after the 5-day regimen and 0.17 +/- 0.10 microgram/mL and 1.57 +/- 3.16 micrograms/mL, respectively, after the 10-day regimen. The mean serum concentration of erythromycin after 10 days was skewed by the data for one of the six patients in the group (concentration of > 8 micrograms/mL). Mean concentrations of erythromycylamine in tonsil tissue were 4.62 +/- 0.97 micrograms/ g after 5 days and 3.47 +/- 2.84 micrograms/g after 10 days. Concentrations in tonsillar tissue were undetectable in all patients given erythromycin for 5 days and in 4 of the 6 patients given erythromycin for 10 days. The high concentrations of erythromycylamine in tonsillar tissue agree with the clinical efficacy seen in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis with dirithromycin.

Steady-state theophylline pharmacokinetic parameters were studied in a panel of 14 patients with chronic obstructive pulmonary disease (COPD). Pharmacokinetic parameters were evaluated before, during, and after a 10-day regimen of the macrolide antibiotic, dirithromycin. The addition of dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline, which were not statistically significant. Mean steady-state plasma theophylline trough concentrations (Css,min) were invariant before, during, and after dirithromycin treatment. Mean average steady-state plasma theophylline concentrations (Cav) declined by 7% during dirithromycin treatment (NS), and mean peak plasma concentrations (Css,max) declined by 12% (NS). Theophylline clearance (CL/F) also remained relatively unchanged during dirithromycin treatment exhibiting an increase of only 11% (NS). Dirithromycin treatment does not significantly affect the steady-state pharmacokinetics of theophylline, and its use in COPD patients is not likely to modify treatment outcomes with theophylline.

The steady-state plasma concentrations and pharmacokinetic characteristics of theophylline were studied during intermittent treatment with dirithromycin. The addition of dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (200 mg every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline. Mean steady-state plasma theophylline trough concentrations (Cmin) were invariant before, during, and after dirithromycin treatment; however, mean average steady-state plasma theophylline concentrations (Cav) declined by 18% during dirithromycin treatment (P less than .05), and mean peak plasma concentrations (Css,max) declined by 26% (P less than .01). Theophylline clearance (CL/F) exhibited an increase of comparable magnitude during dirithromycin treatment, although the increase in CL/F was not statistically significant (.05 less than P less than .1). Dirithromycin treatment alters the steady-state pharmacokinetics of theophylline; however, the magnitude of the changes is small and is not likely to modify treatment outcomes.