Five-year results of non-penetrating deep sclerectomy with demineralized cancellous bone xenogenically derived collagen glaucoma implant

Purpose

To investigate the long-term effectiveness of non-penetrating deep sclerectomy (NPDS) with xenogenically derived cancellous bone collagen glaucoma implant (XCB-CGI) implantation in patients with primary open-angle glaucoma (POAG).

Materials and methods

Retrospective chart review of patients with POAG stages 2 and 3 was treated with NPDS and XCB-CGI. Follow-up was at 6 months, 1, 2, 3, 4 and 5 years after surgery. Main outcomes were intraocular pressure (IOP) and medication burden. Secondary outcomes were visual acuity, corneal hysteresis (CH), visual field (VF) and optical coherence tomography (OCT) parameter analysis.

Results

Among 71 patients (71 eyes), the mean age was 72.7?±?9.8. Average initial IOP was 27.7?±?7.9 and average initial med load was 2.36?±?0.99. At 6 months, 1, 2, 3, 4 and 5 years, the average IOP was 14.9?±?3.3 mm Hg (46.2% reduction), 15.3?±?4.0 mm Hg (44.7% reduction), 14.2?±?3.8 mm Hg (48.7% reduction), 15.2?±?3.3 mm Hg (45.0% reduction), 15.5?±?3.3 mm Hg (44.0% reduction) and 14.2?±?2.8 mm Hg (48.7% reduction), respectively. In 5 years, the success rate was 34% and 67%, without, and with medications (1.8?±?0.8 meds required), respectively. Visual acuity was not significantly different (P?>?.05) at all follow-up visits from baseline. Mean CH increased by 2.1?±?0.8 (P?=?.05). No glaucomatous deterioration of the VF and OCT parameters was detected in 56 eyes at the 5-year follow-up.

Conclusion

NPDS with XCB-CGI implantation is an effective procedure to normalize the level of IOP, stabilize glaucomatous changes and decrease the number of meds needed for glaucoma control.

     

Survival distributions impact the power of randomized placebo-phase design and parallel groups randomized clinical trials

Objectives

The study evaluated the power of the randomized placebo-phase design (RPPD)—a new design of randomized clinical trials (RCTs), compared with the traditional parallel groups design, assuming various response time distributions. In the RPPD, at some point, all subjects receive the experimental therapy, and the exposure to placebo is for only a short fixed period of time.

Study Design and Setting

For the study, an object-oriented simulation program was written in R. The power of the simulated trials was evaluated using six scenarios, where the treatment response times followed the exponential, Weibull, or lognormal distributions. The median response time was assumed to be 355 days for the placebo and 42 days for the experimental drug.

Results

Based on the simulation results, the sample size requirements to achieve the same level of power were different under different response time to treatment distributions. The scenario where the response times followed the exponential distribution had the highest sample size requirement. In most scenarios, the parallel groups RCT had higher power compared with the RPPD.

Conclusion

The sample size requirement varies depending on the underlying hazard distribution. The RPPD requires more subjects to achieve a similar power to the parallel groups design.     

Methods for Measuring Multiple Medication Adherence: A Systematic Review–Report of the ISPOR Medication Adherence and Persistence Special Interest Group

Background

A broad literature base exists for measuring medication adherence to monotherapeutic regimens, but publications are less extensive for measuring adherence to multiple medications.

Structure and characteristics of community‐based multidisciplinary wound care teams in Ontario: An environmental scan

Multidisciplinary team approach is an essential component of evidence‐based wound management in the community. The objective of this study was to identify and describe community‐based multidisciplinary wound care teams in Ontario. For the study, a working definition of a multidisciplinary wound care team was developed, and a two‐phase field evaluation was conducted. In phase I, a systematic survey with three search strategies (environmental scan) was conducted to identify all multidisciplinary wound care teams in Ontario. In phase II, the team leads were surveyed about the service models of the teams. We identified 49 wound care teams in Ontario. The highest ratio of Ontario seniors to wound team within each Ontario health planning region was 82,358:1; the lowest ratio was 14,151:1. Forty‐four teams (90%) participated in the survey. The majority of teams existed for at least 5 years, were established as hospital outpatient clinics, and served patients with chronic wounds. Teams were heterogeneous in on‐site capacity of specialized diagnostic testing and wound treatment, team size, and patient volume. Seventy‐seven percent of teams had members from three or more disciplines. Several teams lacked essential disciplines. More research is needed to identify optimal service models leading to improved patient outcomes.     

Value of Multiparametric MRI in the Work-up of Prostate Cancer

The role of magnetic resonance imaging (MRI) in prostate cancer evaluation is controversial and likely underestimated. Technological advances over the past 5 years have demonstrated that multiparametric MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI, can evaluate the actual tumor burden of a newly diagnosed prostate cancer more accurately than sextant biopsy protocols. Tumor risk, defined by the D’Amico criteria, hence can be re-evaluated by multiparametric MRI. As a result, there is increasing evidence that MRI before repeat or even initial biopsy can accurately select patients who require immediate biopsies and those in whom biopsy could be deferred. Also, a relationship between apparent diffusion coefficient (ADC), calculated from DWI, and Gleason score was found. Thus, MRI before biopsy helps to detect high-grade tumors to target biopsies within areas of low ADC values. To achieve good targeting accuracy, transrectal ultrasound (TRUS)-MRI image registration is necessary. Three-dimensional deformable registration is sufficiently accurate to match TRUS and MRI volumes with a topographic precision of 1 mm. Real-time MRI-guided biopsy is another technique under evaluation. Both approaches will allow for increasing acceptance of focal therapies, should these techniques be validated in the future.     

TRPM8 channel as a novel molecular target in androgen-regulated prostate cancer cells

The cold and menthol receptor TRPM8 is highly expressed in prostate and prostate cancer (PC). Recently, we identified that TRPM8 is as an ionotropic testosterone receptor. The TRPM8 mRNA is expressed in early prostate tumors with high androgen levels, while anti-androgen therapy greatly reduces its expression. Here, from the chromatin-immunoprecipitation (ChIP) analysis, we found that an androgen response element (ARE) mediates androgen regulation of trpm8. Furthermore, using immunofluorescence, calcium-imaging and planar lipid bilayers, we identified that TRPM8 channel is functionally regulated by androgens in the prostate. Although TRPM8 mRNA is expressed at high levels, we found that the TRPM8 protein undergoes ubiquitination and degradation in PC cells. The mass-spectrometry analysis of TRPM8, immunoprecipitated from LNCaP cells identified ubiquitin-like modifier-activating enzyme 1 (UBA1). PYR-41, a potent inhibitor of initial enzyme in the ubiquitination cascade, UBA1, increased TRPM8 activity on the plasma membrane (PM) of LNCaP cells. Furthermore, PYR-41-mediated _PMTRPM8 activity was accompanied by enhanced activation of p53 and Caspase-9. Interestingly, we found that the trpm8 promoter possesses putative binding sites for p53 and that the overexpression of p53 increased the TRPM8 mRNA levels. In addition to the genomic regulation of TRPM8 by AR and p53, our findings indicate that the testosterone-induced _PMTRPM8 activity elicits Ca²⁺ uptake, subsequently causing apoptotic cell death. These findings support the strategy of rescuing _PMTRPM8 expression as a new therapeutic application through the regulation of PC cell growth and proliferation.