RESUMO
We report one- and 2-year results of a prospective, 5-year, multicenter study of radiographic, clinical, and patient-reported outcomes following triplanar first tarsometatarsal arthrodesis with early weightbearing. One-hundred and seventeen patients were included with a mean (95% confidence interval [CI]) follow-up time of 16.6 (15.5, 17.7) months. Mean (95% CI) time to weightbearing in a boot walker was 7.8 (6.6, 9.1) days, mean time to return to athletic shoes was 45.0 (43.5, 46.6) days, and mean time to return to unrestricted activity was 121.0 (114.5, 127.5) days. There was a significant improvement in radiographic measures with a mean corrective change of -18.0° (-19.6, -16.4) for hallux valgus angle, -8.3° (-8.9, -7.8) for intermetatarsal angle and -2.9 (-3.2, -2.7) for tibial sesamoid position at 12 months (n = 108). Additionally, there was a significant improvement in patient-reported outcomes (Visual Analog Scale, Manchester-Oxford Foot Questionnaire, and Patient-Reported Outcomes Measurement Information System) and changes were maintained at 12 and 24 months postoperatively. There was 1/117 (0.9%) reported recurrence of hallux valgus at 12 months. There were 16/117 (13.7%) subjects who experienced clinical complications of which 10/117 (8.5%) were related to hardware. Of the 7/117 (6.0%) who underwent reoperation, only 1/117 (0.9%) underwent surgery for a nonunion. The results of the interim report of this prospective, multicenter study demonstrate favorable clinical and radiographic improvement of the HV deformity, early return to weightbearing, low recurrence, and low rate of complications.
RESUMO
Atazanavir is a first-line HIV protease inhibitor commonly co-dosed with ritonavir. Ritonavir inhibits atazanavir metabolism, decreasing variability and increasing plasma concentrations. However, ritonavir use results in higher costs and increased drug-related adverse events. Elucidating atazanavir pharmacokinetics might allow for individualized ritonavir boosting. We previously demonstrated that genetically determined CYP3A5 nonexpression was associated with slower atazanavir clearance CL/F and higher trough concentrations. This effect was prominent in non-African-American men but absent in African-Americans. The present study considers additional genetic predictors of atazanavir CL/F with a focus on race differences. Nine polymorphisms in CYP3A4, ABCG2, NR1I2 (PXR), and SLCO1B1 were evaluated; 330 plasma samples from 30 HIV-negative volunteers, balanced by sex, race, and CYP3A5 expressor status, were available. Analyses were performed using nonlinear mixed-effects modeling (NONMEM). The following factors were univariately associated with atazanavir CL/F (% effect) : African-American race (decreased 35%), female sex (decreased 25%), older age (decreased 1.7%/year), CYP3A5 nonexpressors (decreased 26%), ABCB1 CGC haplotype carriers (1236C/2677G/3435C) (decreased 33%), and CYP3A4*1B carriers (decreased 31%). However, an independent genetic explanation for the differential race effect could not be identified. An interaction was observed with PXR 63396 C>T and CYP3A5 expressor status (p=0.0002). CYP3A5 nonexpressors with a PXR 63396 CC genotype had 37% slower CL/F versus those with CT or TT genotypes. For CYP3A5 expressors, those with a PXR 63396 CC genotype had 63% faster CL/F versus those with CT or TT genotypes. Although this study has as its main limitation a small overall sample size, these results nonetheless provide new leads and impetus to evaluate ways to individualize the need for ritonavir boosting using demographic and genetic predictors of atazanavir pharmacokinetics.
