盐酸布替萘芬乳膏治疗体股癣和手足癣临床疗效观察

目的观察盐酸布替萘芬乳膏对体股癣和手足癣的疗效。方法盐酸布替萘芬乳膏擦患处,每日1次。疗程体股癣为2周,手足癣为4周,记录临床症状,并做真菌培养。治疗2周复查,4周后随访,进行总体评价。结果体股癣和手足癣患者4周后复查。临床痊愈率分别为94.7%、89.0%、86.0%;总有效率分别为100%、97.8%、93.0%。皮损大部或基本消退,未发现耐药性。结论盐酸布替萘芬乳膏对体股癣和手足癣的疗效良好。     

HPLC测定盐酸布替萘芬乳膏中有关物质的含量

目的建立HPLC测定盐酸布替萘芬乳膏中布替萘芬有关物质的方法。方法以十八烷基键合硅胶为填充剂,流动相为醋酸盐缓冲液-甲醇-异丙醇(17∶70∶13),检测波长282 nm,流速1.0 m L/min。结果布替萘芬有关物质在0.625~5.000μg/m L范围内呈良好的线性关系(r=0.9989),检出限2.6 ng。结论该方法分离效果好,灵敏高,重复性好,可用于盐酸布替萘芬有关物质的含量测定。     

聚山梨酯80对盐酸布替萘芬乳膏微生物限度方法学验证影响的研究

目的 寻找比例合适的稀释剂,提高盐酸布替萘芬乳膏微生物限度方法学验证实验中实验菌的回收率.方法 调整稀释剂pH 7.0氯化钠-蛋白胨缓冲液中聚山梨酯80的比例,按照中国药典2005年版二部微生物限度检查法检查.结果 pH 7.0氯化钠-蛋白胨缓冲液含15%聚山梨酯80的实验菌蚓收牢明显高于含5%,10%,20%聚山梨酯80的回收率.结论 pH 7.0氯化钠-蛋白胨缓冲液含15%聚山梨酯80的实验菌回收率最为适宜.     

聚山梨酯80对盐酸布替萘芬乳膏微生物限度方法学验证影响的研究

目的寻找比例合适的稀释剂,提高盐酸布替萘芬乳膏微生物限度方法学验证实验中实验菌的回收率。方法调整稀释剂pH7.0氯化钠-蛋白胨缓冲液中聚山梨酯80的比例,按照中国药典2005年版二部微生物限度检查法检查。结果pH7.0氯化钠-蛋白胨缓冲液含15%聚山梨酯80的实验菌回收率明显高于含5%,10%,20%聚山梨酯80的回收率。结论pH7.0氯化钠-蛋白胨缓冲液含15%聚山梨酯80的实验菌回收率最为适宜。     

Negatively controlled,randomized clinical trial to evaluate intramammary treatment of nonsevere,gram-negative clinical mastitis

The objective of this negatively controlled, randomized clinical trial was to examine clinical outcomes of 2-d or 8-d treatment using an approved intramammary (IMM) product containing ceftiofur hydrochloride compared with no antimicrobial treatment of nonsevere, gram-negative cases of clinical mastitis (CM). Additionally, we contrasted clinical outcomes of cases caused by Escherichia coli (n = 56) or Klebsiella pneumoniae (n = 54). Cases (n = 168) of nonsevere (abnormal milk or abnormal milk and udder) CM were randomly assigned to receive 2 d (n = 56) or 8 d (n = 56) of IMM ceftiofur or assigned to a negative control group (n = 56). At enrollment, quarter milk samples were collected and used for on-farm culture, somatic cell count (SCC), and confirmatory microbiological analysis. Quarter milk samples were collected weekly from 7 to 28 d after enrollment for microbiological and SCC analysis. Clinical outcomes were followed for 90 d or until the end of lactation (follow-up period, FUP). Overall, no significant differences in quarter-level recurrence of CM (32% for negative control, 34% for the 2-d treatment, and 32% for the 8-d treatment), culling (18% for negative control, 12% for 2-d treatment, and 11% for 8-d treatment), voluntary dry-off of affected quarters (20% for negative control, 30% for 2-d treatment, and 27% for 8-d treatment), days until return to normal milk (4.2 days for negative control, 4.8 days for 2-d treatment, 4.5 days for 8-d treatment), weekly quarter-SCC during the FUP (6.1, 6.3, and 6.0 log₁₀SCC for the negative control, 2-d, and 8-d treatments, respectively), or daily milk yield during the FUP (37.1, 36.3, and 37.6 kg/cow per day for the negative control, 2-d, and 8-d treatments, respectively) were observed among experimental groups. Days of discarded milk were greater for cows assigned to 8-d IMM ceftiofur (11.1 d) than for cows assigned to 2-d (6.9 d) or cows assigned to negative control (5.6 d). Bacteriological cure (BC) at 14 and 21 d after enrollment was greater in cows assigned to 8-d (89%) and 2-d (84%) treatment than in cows assigned to negative control (67%), but this outcome was confounded by pathogen. For CM caused by Kleb. pneumoniae, BC was greater for quarters assigned to receive treatment (combined 2-d and 8-d groups; 74% BC) than for quarters assigned to negative control (18%). In contrast, no differences in BC were observed for CM caused by E. coli (97–98%). Culling and voluntary dry-off of affected quarters were significantly greater for cows with quarters affected by Kleb. pneumoniae (22% culled, 39% voluntary dry-off of quarters) than for cows with quarters affected with E. coli (7% culled, 11% voluntary dry-off of quarters). Overall, use of IMM ceftiofur did not result in improvement of most clinical outcomes, but differences between E. coli and Kleb. pneumoniae were evident. In contrast to E. coli, Kleb. pneumoniae caused chronic intramammary infection and induced worse clinical outcomes. Intramammary antibiotic treatment of most mild and moderate cases of CM caused by E. coli is not necessary, but more research is needed to identify which quarters affected by Kleb. pneumoniae may benefit from antimicrobial therapy.     

Topical ivermectin-metronidazole gel therapy in the treatment of blepharitis caused by Demodex spp.: A randomized clinical trial

PurposeTo evaluate the efficacy of topical ivermectin-metronidazole combined therapy in the management of Demodex-associatedblepharitis.MethodsSixty patients with a diagnosis of Demodex-associatedblepharitis were recruited in a randomized clinical trial. Thirty receiving topical ivermectin (0.1%)-metronidazole (1%) gel treatment on days 0, 15 and 30. Thirty additional patients were used as a control group receiving vehicle on days 0, 15 and 30. The primary efficacy measure was the number of Demodex spp. mitesin the eyelashes of patients. The secondary outcomes included clinical improvement of signs and adverse events.ResultsComplete eradication of Demodex spp. was found in 96.6% of patients in the treatment group. Furthermore, a significant reduction of inflammation signs were found in all treated patients versus controls. None of the patients experienced any adverse effects associated with the treatment.ConclusionDemodex infection was controlled satisfactorily with the ivermectin (0.1%)-metronidazole (1%) gel, and no adverse effects were observed. Application of this gel for the treatment of different parasitic infections of the eyelids could be feasible, and this requires further exploration.     

Negatively controlled,randomized clinical trial to evaluate use of intramammary ceftiofur for treatment of nonsevere culture-negative clinical mastitis

The objective of this negatively controlled randomized clinical trial was to compare clinical outcomes of 5-d intramammary treatment using ceftiofur hydrochloride and no antimicrobial treatment of nonsevere culture-negative cases of clinical mastitis (CM). A total of 121 cases of nonsevere (abnormal milk or abnormal milk and udder) culture-negative CM were randomly assigned to either treatment (n = 62) or negative control (n = 59) groups. Quarters assigned to treatment received 1 daily intramammary infusion with an approved commercially available product containing ceftiofur hydrochloride for 5 d. Quarters assigned to the negative control group did not receive any interventions. Enrolled cows were followed for 90 d or until the end of lactation. At enrollment, milk samples from the affected quarter were used for on-farm culture, somatic cell count (SCC) analysis, and further microbiological analysis. During the follow-up period, milk samples were collected for microbiological analysis and SCC analysis. No significant differences between treatment and negative control groups were identified for treatment failure (5% for treatment vs. 10% for negative control, n = 121), quarter-level CM recurrence (8 vs. 5%, n = 91), intramammary infection at 14 or 28 d after enrollment (13 vs. 26%, n = 86), days until clinical cure (4.2 vs. 4.0 d), days to culling (48.3 vs. 36.8 d), daily milk production (43.3 vs. 43.6 kg/cow per day), or weekly quarter SCC (5.5 vs. 5.4 log₁₀ SCC). Days of milk discard were greater for cows assigned to the treatment group (8.5 d) compared with cows assigned to the negative control group (5.6 d). During the follow-up period, cases in the treatment group had a 50% risk reduction in IMI compared with cases in the negative control group. Irrespective of group, negative outcomes such as quarter-level CM recurrence (12%), treatment failure (12%), and culling (5%) occurred infrequently in nonsevere culture-negative cases of CM. Use of intramammary ceftiofur for treatment of nonsevere culture-negative cases of CM did not improve any economically relevant clinical outcome such as culling, milk production, or SCC.     

Negatively controlled,randomized clinical trial comparing different antimicrobial interventions for treatment of clinical mastitis caused by gram-positive pathogens

The general objective of this study was to evaluate the effect of 3 intramammary antibiotic interventions using 2 commercially available antibiotics with narrow- or broad-spectrum activity on cure rates of clinical mastitis (CM) caused by gram-positive bacteria. We also compared the efficacy of treatment protocols, including a negative control, on outcomes at the cow and mammary quarter level. Before the onset of the study, 5,987 animals more than 12 mo old were randomly preassigned to 1 of 4 protocols in the event of gram-positive CM (except for Staphylococcus aureus and Trueperella pyogenes) during lactation: 3 infusions with 62.5 mg of amoxicillin performed 12 h apart (AMOX-L); 5 infusions once a day with 62.5 mg of amoxicillin (AMOX-EL); 5 infusions once a day with 125 mg of ceftiofur hydrochloride (CEFT-L); or negative control, no treatment performed until 5 d after diagnosis (NEG-CTR). Randomization was performed to preassign 90% of cows to one of the antibiotic protocols (30% in each group) and 10% to the negative control. A total of 696 quarter cases of CM met the inclusion criteria and were evaluated in the study. Quarter-level outcomes were assessed based on 5 milk samples collected up to 14 ± 3 d following enrollment (i.e., first day of treatment), whereas variables at the cow level [composite somatic cell count (SCC), milk production, and survival in the herd] were assessed up to 90 d after CM diagnosis. Streptococcus uberis, followed by Streptococcus dysgalactiae, were the main causes of gram-positive CM. Overall, clinical cure was higher for CEFT-L than for AMOX-EL, and no difference was observed between CEFT-L and AMOX-L. Likewise, no significant differences were detected on overall bacteriological cure, although some treatment effects were observed at the species level. Compared with antibiotic-treated groups, quarters assigned to NEG-CTR had higher counts of colony-forming units (cfu), 16S rRNA gene copy numbers, and Streptococcus relative abundance (RA) until d 5 after enrollment. Quarters treated with AMOX-L had higher cfu counts on d 5, 8, and 14 after enrollment compared with the other antibiotic protocols. In addition, the RA of Streptococcus spp. was higher on d 14 after enrollment for AMOX-treated quarters compared with the CEFT-L group. Linear score of SCC was higher for AMOX-treated cows than for CEFT-L in the first test day after CM. However, cows assigned to AMOX-L had higher milk production than those submitted to the AMOX-EL and CEFT-L protocols. In conclusion, the 2-d protocol with 3 intramammary infusions of amoxicillin (narrow-spectrum antimicrobial) had similar overall clinical and bacteriological cures as 5 administrations (once a day) with ceftiofur hydrochloride (wide spectrum). No significant difference was observed on CM recurrence and cow survival. However, quarters treated with 5-d protocols were more effective at reducing milk cfu counts than quarters in the AMOX-L protocol. In addition, lower Streptococcus spp. RA was observed in ceftiofur-treated quarters compared with the amoxicillin protocols at d 14 after CM diagnosis. Based on results of microbiome and bacterial load (quantitative PCR and cfu count) up to 5 d after CM diagnosis, antibiotic use remains an indispensable strategy for treatment of CM caused by gram-positive bacteria.     

A randomized controlled clinical trial of bupropion SR and individual smoking cessation counseling.

Efficacy of bupropion SR and individual counseling as smoking cessation treatments was assessed in a randomized, placebo-controlled clinical trial among adult daily smokers. Bupropion SR treatment and counseling were fully crossed in this factorial design so that the efficacy of each treatment and the combination could be estimated, relative to a placebo medication and assessment control condition. Intent-to-treat analyses indicated that bupropion SR increased abstinence rates at the end of treatment, relative to the placebo medication conditions, for both biochemically confirmed 7-day point-prevalence abstinence (OR = 1.97, 95% CI 1.04-3.72) and self-reported prolonged abstinence (OR = 2.90, 95% CI 1.66-5.06). Bupropion SR treatment also improved latency to lapse and relapse and improved the latency between lapse and relapse in survival analyses. Medication effects were more modest for both 12-month point-prevalence abstinence (OR = 1.47, 95% CI 0.74-2.92) and prolonged abstinence (OR = 1.34, 95% CI 0.66-2.72). Counseling was not associated with increases in the likelihood of abstinence at any time point (odds ratios ranged from 0.80 to 1.16 across abstinence outcomes in the full intent-to-treat sample). Counseling and medication did not significantly interact at any time point, and adding counseling did not improve end-of-treatment point-prevalence abstinence (OR = 1.17, 95% CI 0.68-2.03) or prolonged abstinence (OR = 1.26, 95% CI 0.75-2.12) substantially when offered in conjunction with active medication.     

Safety and efficacy of lotilaner ophthalmic solution, 0.25% for the treatment of blepharitis due to demodex infestation: A randomized,controlled, double-masked clinical trial

PurposeTo evaluate the safety and efficacy of lotilaner ophthalmic solution, 0.25% for the treatment of blepharitis due to Demodex infestation compared to vehicle control.MethodsIn this phase II, randomized, controlled, double-masked clinical trial, 60 eligible participants with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either topical lotilaner ophthalmic solution, 0.25% (Tarsus Pharmaceuticals, Inc., Irvine, CA) (study group) or the vehicle without lotilaner (control group) bilaterally twice a day for 28 days. Participants were followed at Days 7, 14, 28, 60 and 90. The efficacy parameters were change in collarette grade and Demodex density at Day 28. Safety parameters were adverse events, changes in corrected distance visual acuity (CDVA), intraocular pressure (IOP) and slit-lamp biomicroscopy.ResultsThe study group showed a statistically significant decrease in collarette grade compared to the control group beginning at Day 14 (p = 0.003) in the upper eyelid and at Day 28 (p = 0.003) in the lower eyelid. Decreases in both lids were maintained through Day 90 (p < 0.001). At Day 28, mite eradication was achieved in 66.7% and 25.9% of eyes in the study and control group (p = 0.005); at Day 90, these proportions were 68.2% and 18.5% (p = 0.001), respectively. No serious adverse events or clinically significant changes in CDVA and IOP were observed.ConclusionFor Demodex blepharitis, treatment with lotilaner ophthalmic solution, 0.25% for 4 weeks is safe and effective. The improvement in collarette grade and mite density observed during the treatment period persisted for at least two months following treatment cessation.