The Centers for Disease Control and Prevention have recommended that HIV care clinics incorporate prevention into clinical practice. This report summarizes HIV care providers' attitudes and ...counseling practices before and after they received training to deliver a counseling intervention to patients. Providers at seven HIV clinics received training in delivering a counseling intervention (Positive STEPs) to their patients and completed baseline and follow-up questionnaires to measure changes in prevention parameters. A cohort of patients at each clinic was independently surveyed about counseling experiences. Compared with the pretraining period, providers' self-ratings collected after they initiated the intervention showed significant (p < .05) positive changes in attitudes, comfort, self-efficacy, and frequency of delivering prevention counseling. Patients reported an increase in prevention counseling received from providers after training. The findings indicate that the training and delivery of the Positive STEPs intervention was associated with positive changes in providers' attitudes and HIV prevention counseling to patients.
To evaluate the relative efficacy and safety of 5-fluorouracil (5-FU) and mitomycin C (MMC) when used as adjuncts with primary trabeculectomy in eyes not at high risk for failure.
Prospective ...multicenter, randomized clinical trial.
One hundred thirteen patients with primary open-angle, pseudoexfoliative, pigmentary, or angle-closure glaucoma undergoing primary trabeculectomy were recruited.
One eye of each patient was randomized to receive either 5-FU (50 mg/ml for 5 minutes) or MMC (0.4 mg/ml for 2 minutes).
Intraocular pressure (IOP), visual acuity, complications, and interventions were documented at fixed intervals after surgery. The study also examined progression of visual field loss, long-term complications, and bleb appearance 3 years after surgery.
Of the 108 patients with complete perioperative information, 54 eyes received 5-FU and 54 received MMC. The proportion of patients reaching different predefined target IOPs after surgery was slightly higher in the MMC group than in the 5-FU group. This difference was less than 25%, which would have been necessary to achieve statistical significance with a power of 0.8 and the sample size used. Likewise, there was no statistically significant difference between the groups with regard to mean preoperative IOP, complications, or interventions. Mean postoperative follow-up was 309 and 330 days in the 5-FU and MMC groups, respectively (
P = 0.593).
5-Fluorouracil and MMC were found to be equally safe and effective adjuncts to primary trabeculectomy in the short- and medium-term postoperative periods.
Ibrutinib, a once-daily oral inhibitor of Bruton tyrosine kinase, has greatly improved outcomes for patients with chronic lymphocytic leukemia (CLL). The phase 3 RESONATE trial, which compared ...single-agent ibrutinib to ofatumumab in high-risk, relapsed patients with CLL, provided support for approval of ibrutinib in the United States and Europe. We describe long-term follow-up of patients treated in RESONATE, where continued superiority of progression-free survival (PFS) (hazard ratio HR, 0.133; 95% confidence interval CI, 0.099-0.178) was observed. Overall survival benefit continues (HR, 0.591; 95% CI, 0.378-0.926), although with decreased magnitude relative to that seen before crossover to ibrutinib was implemented for patients on ofatumumab (HR, 0.426; 95% CI, 0.220-0.823). Notably, overall response to ibrutinib increased over time, with 91% of patients attaining a response. The PFS benefit with ibrutinib was independent of baseline risk factors, although patients with ≥2 prior therapies had shorter PFS than those with <2 prior therapies, and the presence of TP53 or SF3B1 mutations showed a trend toward shorter PFS vs without these factors. Median duration of ibrutinib was 41 months, with 46% remaining on treatment at a median follow-up of 44 months. Grade ≥3 adverse events generally decreased over time, causing only a small proportion of patients to cease therapy. Ibrutinib was discontinued due to progressive disease in 27% of patients. This long-term study provides support for sustained efficacy and safety of ibrutinib in relapsed/refractory CLL and consideration of study provisions that allow crossover to investigational therapy when benefit has been clearly demonstrated. This trial was registered at www.clinicaltrials.gov as #NCT01578707.
•Extended ibrutinib treatment showed sustained PFS in previously treated patients with CLL, including those with high-risk cytogenetics.•Overall survival outcomes were sustained and no long-term safety signals have emerged with 4 years of follow-up on ibrutinib treatment.
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Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic ...lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months. Pharmacokinetic assessment of ibrutinib exposure at 420-mg dose suggested similar exposure regardless of patient weight or age. As assessed by independent review committee, patients with higher DI experienced longer median progression-free survival (PFS) compared with those with lower DI regardless of del17p and/or TP53 status. Of 79 patients requiring a drug hold, treatment was restarted at the original dose in 73 (92%) patients. Mean duration of a missed-dose event was 18.7 days (range, 8-56). Patients missing ≥8 consecutive days of ibrutinib had a shorter median PFS vs those missing <8 days (10.9 months vs not reached). These results support sustained adherence to once-daily ibrutinib dosing at 420 mg as clinically feasible to achieve optimal outcomes in patients with previously treated CLL. The trial was registered at www.clinicaltrials.gov as #NCT01578707.
•Higher ibrutinib DI is associated with improved PFS, independent of del17p or TP53 mutation.•Ibrutinib hold for >1 week, often needed to manage adverse events, is associated with increased PFS events.
Nuclear export of unspliced and singly spliced viral mRNA is a critical step in the HIV life cycle. The structural basis by which the virus selects its own mRNA among more abundant host cellular RNAs ...for export has been a mystery for more than 25 years. Here, we describe an unusual topological structure that the virus uses to recognize its own mRNA. The viral Rev response element (RRE) adopts an “A”-like structure in which the two legs constitute two tracks of binding sites for the viral Rev protein and position the two primary known Rev-binding sites ∼55 Å apart, matching the distance between the two RNA-binding motifs in the Rev dimer. Both the legs of the “A” and the separation between them are required for optimal RRE function. This structure accounts for the specificity of Rev for the RRE and thus the specific recognition of the viral RNA.
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•The 233 nucleotide RRE of HIV-1 folds into an “A”-like structure•The two “legs” of the “A” consist of two main segments of the RRE structure•The two known Rev primary binding sites are about 55 Å apart•Both segments must be present for Rev oligomerization and HIV export function
A unique “A” shaped structure found in RNA’s from HIV explains how they are selectively chosen for nuclear export by the viral protein Rev.
Neuroendocrine tumors Clark, Orlo H; Ajani, Jaffer; Benson, 3rd, Al B ...
Journal of the National Comprehensive Cancer Network
4, Številka:
2
Journal Article
Purpose
Physical and digital phantoms play a key role in the development and testing of nuclear medicine instrumentation and processing algorithms for clinical and research applications, including ...neuroimaging using positron emission tomography (PET). We have developed and tested a digital reference object (DRO) version of the original segmented magnetic resonance imaging (MRI) data used for the three‐dimensional (3D) PET brain phantom developed by Hoffman et al., which is used as the basis of a commercially available physical test phantom.
Methods
The DRO was constructed by subdividing the MRI image planes the original phantom was based on to create equal‐thickness slices and re‐labeling voxels. The digital data was then embedded in a PET Digital Imaging and Communications in Medicine format and tested for compliance.
Results
We then tested the DRO by comparing it to computed tomography (CT) images of the physical phantom summed to form composite slices with axial extent similar to the DRO, but with a factor of two better in‐slice resolution. For composite slices, 91% of voxels were labeled in full agreement, 5% of the voxels were 50–75% accurate, and the remaining 4% of voxels had 25% or less agreement.
Conclusions
This DRO can be used as an input for PET scanner simulation studies or for comparing simulations to measured Hoffman phantom images.
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