Study Designs for Evaluation of Combination Treatment: Focus On Individual Patient Benefit

Combination treatment, i.e., the use of two or more drugs for the same condition, is frequent in medicine if monotherapy yields an insufficient therapeutic response. We here review and challenge clinical study designs and formats of reporting outcomes for the evaluation of the benefit/risk ratio of combination treatment over monotherapy. We demonstrate that benefits of combination treatment at the group level over-estimate the probability of benefit at the single patient level based on outcome simulations under almost any imaginable setting. Based on these findings we propose that studies testing combination treatment should always report on percentages of responders to monotherapy and combination treatment. We provide equations that allow calculation of the percentage of patients truly benefitting from combination (responders to both monotherapies) and that of patients exposed to risk of harm from adverse effects without a reasonable expectation of individual benefit. These considerations are explained based on real clinical data, mostly from the field of functional urology (male lower urinary tract symptoms).

Examining the Utility of the LSI-R in a Sample of Women who have Sexually Offended

The ability to identify factors predictive of recidivism among individuals who have offended is integral to properly targeting supervision and treatment focus. Instruments such as the Level of Service Inventory–Revised (LSI-R) show promise with general justice-involved females, but no study to our knowledge has assessed it with women who have sexually offended. The purpose of this study is to examine the utility of the LSI-R in a sample of 243 women from the State of Texas who have sexually offended. Results indicate that the total score was significantly related to criminal recidivism (Harrell’s C = .67) and any recidivism (Harrell’s C = .65). Analyses of the subscales indicated that criminal history and alcohol/drug subscales were significantly related to all forms of recidivism, while the education/employment and financial scales were significantly related to criminal recidivism and any recidivism. These results provide insight into risk assessment and treatment for women who have sexually offended.

Immunotherapy in Metastatic Mucosal Melanoma with Disseminated Intravascular Coagulation: A Case of Success

Mucosal melanoma accounts for 1% of all melanomas. It is more aggressive than cutaneous melanoma, and local excision provides the best disease-free survival. The vast majority of patients eventually develop metastases, with a metastatic pattern independent of the primary tumor site. While studies show that BRAF and KIT inhibitors have a role in the management of these patients, the actual treatment focus is on immunotherapy. Herein is described the case of a 79-year-old woman with metastatic mucosal melanoma and bone marrow infiltration causing disseminated intravascular coagulation, who was treated with an immunotherapy combination (anti-CTLA-4 and anti-PD-1 antibodies), achieving complete disease remission. This is the third case of melanoma with disseminated intravascular coagulation at presentation and the second case treated with immunotherapy in the literature, but the only one achieving disease remission.

Varicocele and male infertility: Historical, anatomical and urological perspectives – a mini review

Varicocele is defined as an abnormal dilatation of the pampiniform plexus of the spermatic cord. This is seen in 10 to 20% of general population and is one of the most common correctable causes of male infertility. The history of varicocele dates back to the era of Ancient Greeks to about 600 BC, who had sculptured varicocele in their statues as a tortuous bag of wormsin the scrotum. It was Ambrose Pare who gave a poetic description to the pooling of blood in the spermatic cords and subsequently Curling coined the term Varicocele The intricacy of the venous drainage of the scrotum and its contents and the criss crossing of the veins makes the thermo-regulatory mechanism regulating spermatogenesis, even more complex. The Cremaster and Dartos greatly aid in facilitating the thermo-regulatory mechanism of scrotal wall, which forms the anatomical basis of oligospermia in patients with varicocele. Apart from a visible change in seminal parameters, the benefits of varicocelectomy have extended on to an improvement in serum testosterone and enhancement of erectile and ejaculatory functions. With a greater knowledge of the pathophysiology of varicocele and with better understanding of the roles of gene polymorphisms and reactive oxygen species, the indications for varicocelectomy gain more support and evidence. A sound anatomical knowledge and an in-depth understanding of the events that take place at molecular level might shift the treatment focus in future from varicocelectomy to molecular targeted therapies.