Despite the perception that diabetes management was more difficult in college, metabolic control was maintained during college, possibly due to a more intensive treatment approach.

Sexual dysfunction is a complaint of 30-50% of American women. Aside from hormone replacement therapy, there are no current FDA-approved medical treatments for female sexual complaints. The goal of this pilot study was to determine safety and efficacy of sildenafil for use in women with sexual arousal disorder (SAD). Evaluations were completed on 48 women with complaints of SAD. Physiologic measurements, including genital blood flow, vaginal lubrication, intravaginal pressure-volume changes, and genital sensation were recorded pre- and postsexual stimulation at baseline and following 100 mg sildenafil. Subjective sexual function was assessed using a validated sexual function inventory at baseline and following 6 weeks of home use of sildenafil. At termination of the study patients also completed an intervention efficacy index (FIEI). Following sildenafil, poststimulation physiologic measurements improved significantly compared to baseline. Baseline subjective sexual function complaints, including low arousal, low desire, low sexual satisfaction, difficulty achieving orgasm, decreased vaginal lubrication, and dyspareunia also improved significantly following 6 weeks home use of sildenafil. Sildenafil appears to significantly improve both subjective and physiologic parameters of the female sexual response. Double-blind, placebo-controlled studies are currently in progress to further determine efficacy of this medication for treatment of female sexual dysfunction complaints in different populations of women.

PURPOSE Combination treatment with BRAF and MEK inhibitors has demonstrated benefits on progression-free survival (PFS) and overall survival (OS) and is a standard of care for the treatment of advanced BRAF V600–mutant melanoma. Here, we report the 5-year update from the COLUMBUS trial (ClinicalTrials.gov identifier: NCT01909453 ). METHODS Patients with locally advanced unresectable or metastatic BRAF V600–mutant melanoma, untreated or progressed after first-line immunotherapy, were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, vemurafenib 960 mg twice daily, or encorafenib 300 mg once daily. An updated analysis was conducted 65 months after the last patient was randomly assigned. RESULTS Five hundred seventy-seven patients were randomly assigned: 192 to encorafenib plus binimetinib, 191 to vemurafenib, and 194 to encorafenib. The 5-year PFS and OS rates with encorafenib plus binimetinib were 23% and 35% overall and 31% and 45% in those with normal lactate dehydrogenase levels, respectively. In comparison, the 5-year PFS and OS rates with vemurafenib were 10% and 21% overall and 12% and 28% in those with normal lactate dehydrogenase levels, respectively. The median duration of response with encorafenib plus binimetinib was 18.6 months, with disease control achieved in 92.2% of patients. In comparison, the median duration of response with vemurafenib was 12.3 months, with disease control achieved in 81.2% of patients. Long-term follow-up showed no new safety concerns, and results were consistent with the known tolerability profile of encorafenib plus binimetinib. Interactive visualization of the data presented in this article is available at COLUMBUS dashboard. CONCLUSION In this 5-year update of part 1 of the COLUMBUS trial, encorafenib plus binimetinib treatment demonstrated continued long-term benefits and a consistent safety profile in patients with BRAF V600–mutant melanoma.

Staphylococcus aureus nasal carriage is a risk factor for infection in humans, particularly in the hospital environment. Attenuation of carriage has proven effective in reducing the prevalence of infection in some high-risk groups. To study staphylococcal factors that influence nasal colonization, a mouse model of S. aureus nasal colonization was developed. Mice were inoculated intranasally with S. aureus Reynolds, and nasal carriage was evaluated by quantitating cultures of the nasal tissues from mice sacrificed at various time points after inoculation. The majority of mice inoculated with 108 CFU of S. aureusmaintained nasal carriage for at least 20 days. Nasal colonization rates were similar for inbred (BALB/c and C57BL/6) and outbred (ICR) mice. Colonization was not affected by mouse passage of strain Reynolds. Lower inoculum doses (<107 CFU) resulted in reduced colonization after 7 days. However, mice given streptomycin in their drinking water developed long-term carriage of S. aureus, and they were colonized with inocula as low as 105 CFU. Nasal colonization was also established with two other S. aureus strains (one strain each of human and murine origins). S. aureus recovered from the nares of experimentally colonized mice expressed high levels of capsule, and the ability of a capsule-defective mutant to persist in the nares was reduced in comparison to that of the parent strain. This nasal colonization model should prove useful for studies of factors that mediate S. aureus colonization and for assessment of targets for antimicrobial intervention or vaccine development.

We evaluated the ability of intravenous supplementation therapy with alpha(1)-antitrypsin (AAT) to reduce the rate of urinary excretion of desmosine (DES), a specific marker of elastin degradation, in eight men and four women with emphysema due to severe, congenital deficiency of AAT (range 17-69 mg/dl). Nine were former cigarette smokers, two were current smokers, and one reported never smoking; their mean age was 54 (SD 12) yr and their mean FEV(1) was 41 (18%) of predicted. Urinary DES was measured by isotope dilution and HPLC. Prior to the start of AAT supplementation, mean DES excretion was 13.0 (5.0) microg/g creatinine, 73% higher than in healthy nonsmokers. During 8 wk of supplementation therapy, mean urinary DES excretion was 13.0 (5.9) microg/g creatinine, unchanged from the baseline period (p = 0.85 by repeated measures ANOVA). We conclude that baseline levels of elastin degradation in emphysematous patients with severe AAT deficiency were abnormally high and that 8 wk of AAT supplementation therapy did not appreciably reduce the rate of elastin degradation. These findings raise the possibilities that protective levels of AAT in the lungs are insufficient or that elastin degradation in the lungs of these subjects is not dependent upon neutrophil elastase at this time.