Platelet Cyclic Guanosine Monophosphate as a Biomarker of Phosphodiesterase Type 5 Inhibitor Efficacy in the Treatment of Erectile Dysfunction: A Randomized Placebo-Controlled Study

Background

Phosphodiesterase 5 inhibitors (PDE5-Is) are a mainstay in the therapy of erectile dysfunction (ED). The primary end point of clinical efficacy, both in clinical studies and normal practice, is represented by the International Index of Erectile Function (IIEF).

Objective

To evaluate if platelet cyclic guanosine monophosphate (cGMP) could represent a valuable marker for PDE5-I activity in ED.

Design, setting, and participants

The study enrolled 46 patients with psychogenic, organic, and mixed ED (20–71 yr of age; IIEF score <26). Patients were randomized to 6 wk of vardenafil, 5 mg/d at bedtime, or placebo.

Intervention

All patients donated two blood samples, one before starting the protocol and the second after 6 wk of treatment.

Measurements

Platelet cGMP was measured in both placebo and vardenafil groups. All the patients completed the IIEF-Erectile Function (EF) domain and the sexual encounter profile (SEP) and underwent visual sexual stimulation (VSS) coupled with Rigiscan. All the measurements were performed prior to starting the protocol and after the 6 wk of treatment.

Results and limitations

Platelet cGMP production was significantly (p < 0.05) elevated in patients taking 5 mg vardenafil versus placebo. Vardenafil was not superior to placebo in improving IIEF-EF and SEP scores. Conversely, VSS-Rigiscan revealed a significant amelioration (p < 0.028) in the vardenafil group versus placebo. The changes in platelet cGMP level correlated well with VSS-Rigiscan (p = 0.0037) but not with IIEF-EF and SEP.

Conclusions

Platelet cGMP could represent a relatively simple, reliable, and objective biomarker of PDE5-I activity in ED clinical studies. Larger clinical studies are needed to further validate the use, utility, and limits of this assay.     

Histopathologic excision margin affects local recurrence rate: analysis of 2681 patients with melanomas < or =2 mm thick

OBJECTIVE: Prospective trials have shown that 1-cm and 2-cm margins are safe for melanomas <1 mm thick and > or =1 mm thick, respectively. It is unknown whether narrower margins increase the risk of LR or mortality. SUMMARY BACKGROUND DATA: To determine the relationship between histopathologic excision margin, local recurrence (LR) and survival for patients with melanomas < or =2 mm thick. METHODS: Data were extracted from the Sydney Melanoma Unit database for all patients with cutaneous melanoma < or =2 mm thick, diagnosed up to 1996. Patients with positive excision margins or follow-up <12 months were excluded, leaving 2681 for analysis. Outcome measures were LR (recurrence <5 cm from the excision scar), in-transit recurrence, and disease-specific survival. Factors predicting LR and overall survival were tested with Cox proportional hazards analysis. RESULTS: Median follow-up was 83.8 months. LR was identified in 55 patients (median time to recurrence, 37 months). At 120 months, the actuarial LR rate was 2.9%. Five-year survival after LR was 52.8%. In multivariate analysis, only margin of excision and tumor thickness were predictive of LR (both P = 0.003). When all patients with a margin <0.8 cm in fixed tissue (corresponding to a margin of <1 cm in vivo) were excluded from analysis, margin was no longer significant in predicting LR. Thickness, ulceration, and site were predictive of survival, but margin was not (P = 0.49). CONCLUSIONS: Histopathologic margin affects the risk of LR. However, if the in vivo margin is > or =1 cm, it no longer predicts risk of LR. Patient survival is not affected by margin.     

Strabismus in adults with uveal melanoma following episcleral plaque brachytherapy

PURPOSE: To ascertain the incidence of persistent strabismus in patients treated with plaque brachytherapy and its subsequent treatment. METHODS: A single center retrospective case note review of adult patients with persistent diplopia or strabismus following plaque brachytherapy for all types of intraocular tumors between 1996 and 2004. RESULTS: A total of 929 consecutive adults underwent plaque brachytherapy during the study period at a single center. Sixteen patients (1.7%) with treated uveal melanoma developed persistent diplopia or strabismus. In 11 patients (69%) the timing of onset was in the first year, in 2 (13%) in the second year, and one each (6% each) in years 5, 7, and 8. Two patients (13%) did not require any intervention. Fourteen patients (88%) required treatment: 7 (50%) were treated with prisms only, 3 (21%) underwent botulinum toxin (BTXA) injections, and 4 (29%) were treated with extraocular muscle surgery (3 required one operation and one required 2 procedures). CONCLUSIONS: The incidence of ocular motility disorders following plaque brachytherapy in our cohort was 1.7% over 8 years and we include this in the consent process for conservative treatment of intraocular tumors. Options for treatment for persistent diplopia or strabismus include prisms, botulinum toxin injection, or surgery.     

Scheimpflug imaging to determine intraocular lens power in vivo

PURPOSE: To assess the feasibility of determining intraocular lens (IOL) power by measurement of the central optic thickness using clinically available Scheimpflug imaging (Pentacam, Oculus). SETTING: King's College Hospital Ophthalmology Department, London, United Kingdom. METHODS: Sixty-seven eyes were assessed 1 month after uneventful phacoemulsification with in-the-bag implantation of AcrySof MA60AC IOLs (Alcon). The correlation between IOL thickness measurement and IOL power was calculated. Repeatability of central optic thickness measurement was determined from 10 successive scans of 4 patients. RESULTS: Within-subject standard deviation increased with the subject mean. The coefficient of variability was 1.4%. Measured lens thickness was highly correlated with lens power (R(2) = 0.94, P<.001). Over the measured range, 95% confidence intervals varied between +/-0.83 diopters (D) and +/-0.92 D. CONCLUSIONS: Central IOL thickness measurements with the Pentacam Scheimpflug camera were highly repeatable and closely correlated with the known IOL power. The IOL power, calculated from a regression equation, is likely to be less than +/-1.00 D away from the actual power. Approximate in vivo IOL power determination is feasible with clinically available Scheimpflug imaging. This could be applied clinically in cases of unexplained postoperative refractive error.     

Human telomerase RNA component expression in Spitz nevi,common melanocytic nevi,and malignant melanomas

BACKGROUND: Telomerase is a ribonucleoprotein DNA polymerase that is capable of synthesizing telomeres onto the ends of chromosomes. The cumulative loss of telomerase activity is believed to be associated with cell senescence. Telomerase activity has been shown to be higher in malignant melanomas than in common melanocytic nevi. The aim of the present study was to elucidate the pattern of expression of the human telomerase RNA (hTER) component in routinely processed specimens of Spitz nevi, malignant melanomas, and ordinary melanocytic nevi. METHODS: Ten specimens of each type of tumor were studied, using an in situ hybridization technique. RESULTS: All three types of tumors demonstrated moderate to high intensities of hTER expression, usually in more than half of the tumor cells, and the majority of the studied lesions in each group did not show stratification of staining. The hTER component was also detected in the epidermis, sweat glands, and pilosebaceous units. CONCLUSIONS: hTER levels do not necessarily correlate with the level of telomerase activity, and the level and pattern of hTER expression are not useful as an adjunct to the histologic differential diagnosis of Spitz nevi from melanocytic nevi and malignant melanomas.     

How does feedback from patients impact upon healthcare student clinical skill development and learning? A systematic review

Background: A key feature of health professionals’ training, irrespective of discipline, is the acquisition and application of clinical and communication skills. Despite this, little is known about the potential role of patient feedback on this process. This systematic review aimed to answer the question: How does feedback from patients impact upon healthcare student clinical skill development and learning?

Design: Systematic review of published literature.

Methods: Electronic databases were searched for studies that explored the effects of patient feedback on student learning and were published before March 2016. Eligible articles underwent methodological evaluation using the McMaster University Critical Evaluation Forms and data extraction.

Results: A total of 237 articles were retrieved following searches of electronic databases and hand searches of reference lists. Twelve (7 quantitative, 2 qualitative, 3 mixed methods) studies met the inclusion criteria. Eleven studies reported that patient feedback improved students’ clinical skills.

Conclusion: Minimal research has explored the impact of patient feedback on student learning. The research to date suggests that direct feedback from patients may be beneficial for the development of students’ communication and clinical skills; however, the wide variety of evaluation methods and the lack of validated tools for patients to provide feedback suggest that further exploration is warranted.