Once-daily 0.1% mometasone furoate cream versus twice-daily 0.1% betamethasone valerate cream in the treatment of a variety of dermatoses

A randomized, investigator-blind, parallel-group trial was conducted to compare the safety and efficacy of 0.1% mometasone furoate cream applied once daily with that of 0.1% betamethasone valerate cream applied twice daily in patients (n = 69) with allergic contact dermatitis, atopic dermatitis and other steroid-responsive dermatoses. After 3 day's treatment improvement in conditions averaged 38.2% and 39.3%, respectively, in the mometasone and betamethasone treatment groups, and after 21 days average improvements were 93.6% and 96.5%, respectively. The physicians' global evaluation of overall change in disease status and the patients' evaluation of treatment also indicated that the two treatment regimens produced comparable, rapid and progressive improvements in the patients' conditions, and no local side-effects were reported. It is concluded that mometasone furoate was as effective as betamethasone valerate in the treatment of a variety of steroid-responsive dermatoses, although mometasone furoate was applied only half as frequently.     

A randomized trial of combination therapy with intralesional interferon alpha 2b and podophyllin versus podophyllin alone for the therapy of anogenital warts

To determine the value of combining interferon with standard local therapy in the treatment of human papillomavirus infection, 97 patients with anogenital warts were randomized to a short course of either interferon plus podophyllin or podophyllin alone. Interferon alpha 2b (1.5 x 10(6) IU) was injected intralesionally and podophyllin resin applied topically to each of three warts once weekly for 3 weeks. Maximal responses occurred within 2 weeks of therapy, and overall there was complete clearance of treated warts in 67% of interferon and podophyllin versus 42% of podophyllin recipients (P less than .05, chi 2). Clearance rates were greater in women, patients with warts of less than or equal to 12 months' duration, and HIV-seronegative patients. Of patients with complete clearance, 67% of interferon and podophyllin and 65% of podophyllin recipients experienced recurrences. Thus, in short treatment courses of anogenital warts, intralesional interferon enhanced the effect of topical podophyllin, and trials of combination therapy using more intensive or prolonged regimens of interferon are warranted.     

Effect of tacrolimus (FK506) and sirolimus (rapamycin) mono- and combination therapy in prolongation of renal allograft survival in the monkey

BACKGROUND: Our previous studies confirmed that tacrolimus (FK506) and sirolimus [rapamycin (RAPA)], in combination, are not antagonistic but are synergistic in the prolongation of heart and small bowel grafts in the rodent. The aim of this study was to confirm further the synergistic effect of combined FK506 and RAPA in the more clinically relevant model, kidney transplantation in monkeys. METHODS: A total of 60 male Vervet monkeys were randomly assigned to 10 groups (n> or =5). Monkeys with renal allografts were treated with different doses of FK506 and/or RAPA orally for 60 days. Graft survival, body weight, clinical biochemistry determinations, oral glucose tolerance test, trough levels of the two drugs, and histopathology were investigated. RESULTS: Low doses of FK506 (1 or 4 mg/kg) combined with RAPA (0.5 mg/kg) produced synergistic effect in the prolongation of renal graft survival [combination index (CI) = 0.292, 0.565]. There were no additive or synergistic drug-associated toxicities such as hyperglycemia, nephrotoxicity, and hyperlipidemia. There also was no pharmacological antagonism. CONCLUSION: Concomitant therapy of low-dose (drug-optimal) FK506 and RAPA produced a synergistic effect in the prolongation of kidney allograft survival in Vervet monkeys without additive drug-associated toxicities.     

Sulfhydryl Reactivity: Mechanism of Action of Several Antiviral Compounds—Selenocystine, 4-(2-Propinyloxy)-β-Nitrostyrene, and Acetylaranotin

The addition of 5 mM dithiothreitol to a cell-free assay system for influenza ribonucleic acid (RNA) polymerase activity reverses the inhibitory activity otherwise possessed by three established antiviral compounds: selenocystine, 4-(2-propinyloxy)-beta-nitrostyrene, and acetylaranotin. Although 50% or greater enzyme inhibitory activity is repeatedly achieved for these compounds at a concentration of approximately 50 mug/ml (0.1 to 0.25 mM) in the absence of dithiothreitol, no inhibition is seen in its presence at inhibitor concentrations as high as 200 mug/ml. Against the deoxyribonucleic acid-directed RNA polymerases of Escherichia coli and chicken embryo cells, acetylaranotin and 4-(2-propinyloxy)-beta-nitrostyrene caused very little inhibition. Only selenocystine significantly inhibited these two enzymes in the absence of reducing agent, but to an extent substantially less than that obtained against the viral enzyme. These results appear to suggest that influenza RNA polymerase is uniquely sensitive to a variety of structurally diverse antiviral compounds as a consequence of their sulfhydryl reactivity-a fact which might aid in the search for and development of more potent chemotherapeutic agents.     

Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy.

BACKGROUND AND DESIGN--Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS--Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS--This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.     

So much to teach,so little time: a prospective cohort study evaluating a tool to select content for a critical care curriculum

Introduction  

Curricular content is often based on the personal opinions of a small number of individuals. Although convenient, such curricula may not meet the needs of the target learner, the program or the institution. Using an objective method to ensure content validity of a curriculum can alleviate this issue.     

Teachers’ Promotion or Inhibition of Children’s Aggression Depends on Peer-Group Characteristics

Researchers have increasingly started to pay attention to how contextual factors, such as the classroom peer context and the quality of student–teacher interactions, influence children’s aggressive behavior. This longitudinal study was designed to examine the degree to which benefits and costs of different teaching practices (child-centered and child-dominated) would be dependent on the initial peer-group composition (aggregate levels of aggression and victimization at the beginning of first grade). Teachers provided ratings of aggression and victimization (N = 523 first-grade students; M age at the beginning of first grade = 7.49 years, SD = 0.52). Information about different teaching practices was obtained via observations. Our results show that whereas child-centered practices are beneficial in high-victimization classrooms, child-dominated practices inhibit the development of aggression in low-victimization classroom contexts. Our findings highlight the importance of moving beyond main-effect models to studying how different contextual influences interact to promote, or inhibit, the development of aggression.     

Changes in residents’ opportunities for experiential learning over time

Medical Education 2012: 46 : 1189–1193 Context Learning in the clinical environment is believed to be a crucial component of residency training. However, it remains unclear whether recent changes to postgraduate medical education, including the implementation of work hour limitations, have significantly impacted opportunities for experiential learning. Therefore, we sought to quantify opportunities to gain clinical experience within medical‐surgical intensive care units (ICUs) over time. Methods Data on the numbers of patients admitted and invasive procedures performed per day between 1 July 2001 and 30 June 2010 within three academic medical‐surgical ICUs in Calgary, Alberta, Canada were obtained from electronic medical records. These data were matched to resident doctor on‐call schedules and residents’ opportunities to admit patients and participate in procedures were calculated and compared over time using Spearman’s rho. Results We found that over a 9‐year period, the opportunities afforded to residents (n = 1156) to admit patients (n = 17 189) and perform procedures (n = 52 827) during ICU rotations decreased by 32% (p < 0.001) and 34% (p < 0.001), respectively. Conclusions Our results suggest that there has been a significant decrease in residents’ clinical experiences in the ICU over time. Further investigations to better understand these changes and how they may impact on performance as residents become independent practising doctors are warranted.     

Influence of residency training on multiple attempts at endotracheal intubation

Purpose

Endotracheal intubation (ETI) of critically ill patients is a high-risk procedure that is commonly performed by resident physicians. Multiple attempts (≥2) at intubation have previously been shown to be associated with severe complications. Our goal was to determine the association between year of training, type of residency, and multiple attempts at ETI.

Methods

This was a cohort study of 191 critically ill patients requiring urgent intubation at two tertiary care teaching hospitals in Vancouver, Canada. Multivariable logistic regression was used to model the association between postgraduate year (PGY) of training and multiple attempts at ETI.

Results

The majority of ETIs were performed for respiratory failure (68.6%) from the hours of 07:00–19:00 (60.7%). Expert supervision was present for 78.5% of the intubations. Multiple attempts at ETI were required in 62%, 48%, and 34% of patients whose initial attempt was performed by PGY-1, PGY-2, and PGY-3 non-anesthesiology residents, respectively. Anesthesiology residents required multiple attempts at ETI in 15% of patients, regardless of the year of training. The multivariable model showed that both higher year of training (risk ratio [RR] 0.74; 95% confidence interval [CI] 0.54-0.93; P < 0.01) and residency training in anesthesiology (RR 0.52; 95% CI 0.20-1.0; P = 0.05) were independently associated with a decreased risk of multiple intubation attempts. Finally, intubations performed at night were associated with an increased risk of multiple intubation attempts (RR 1.3; 95% CI 1.0-1.4; P = 0.03).

Conclusion

Year of training, type of residency, and time of day were significantly associated with multiple tracheal intubation attempts in the critical care setting.