A systematic review and meta-analysis of placebo effect in clinical trials on chronic prostatitis/chronic pelvic pain syndrome.

BACKGROUND: It is a common practice to control efficacy of pharmacological treatment with a placebo group. However, placebo itself may affect subjective and even objective results. The purpose of this study was to evaluate the placebo effect on symptoms of CP/CPPS to improve future clinical trials. METHODS: A search at three databases (Scopus, MEDLINE, and Web of Science) was conducted to identify double-blind placebo-controlled clinical trials on the treatment of CP/CPPS published until April 2021. The primary outcome - National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score. SECONDARY OUTCOMES: Qmax, PVR, IPSS, and prostate volume. RESULTS: A total of 3502 studies were identified. Placebo arms of 42 articles (5512 patients, median 31 patients) were included in the systematic review. Systematic review identified positive changes in the primary endpoint, meta-analysis of 10 articles found that NIH-CPSI total score results were significantly influenced by placebo, mean difference -4.2 (95% confidence interval [CI]: -6.31, -2.09). Mean difference of NIH-CPSI pain domain was -2.31 (95% CI: -3.4, -1.21), urinary domain -1.12 (95% CI: -1.62, -0.62), quality of life domain -1.67 (95% CI: -2.38, -0.96); p < 0.001 for all. In case of the objective indicator - Qmax, there were three articles included in the meta-analysis. Qmax mean change from baseline was 0.68 (95% CI: -0.85, 2.22, p = 0.38). Systematic review showed no significant changes in pain, measured by VAS or other scores, IPSS and PVR. CONCLUSIONS: Placebo significantly affected the subjective parameters (NIH-CPSI) and limitedly affected various other measurements of pain (visual analog scale, McGill pain questionnaire). There was no long-term effect on IPSS and objective measurements (Qmax, PVR). This study can be used in further clinical trials to develop general rules of CPPS treatment assessment.

MRI-derived PRECISE scores for predicting pathologically-confirmed radiological progression in prostate cancer patients on active surveillance.

OBJECTIVES: To assess the predictive value and correlation to pathological progression of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scoring system in the follow-up of prostate cancer (PCa) patients on active surveillance (AS). METHODS: A total of 295 men enrolled on an AS programme between 2011 and 2018 were included. Baseline multiparametric magnetic resonance imaging (mpMRI) was performed at AS entry to guide biopsy. The follow-up mpMRI studies were prospectively reported by two sub-specialist uroradiologists with 10 years and 13 years of experience. PRECISE scores were dichotomized at the cut-off value of 4, and the sensitivity, specificity, positive predictive value and negative predictive value were calculated. Diagnostic performance was further quantified by using area under the receiver operating curve (AUC) which was based on the results of targeted MRI-US fusion biopsy. Univariate analysis using Cox regression was performed to assess which baseline clinical and mpMRI parameters were related to disease progression on AS. RESULTS: Progression rate of the cohort was 13.9% (41/295) over a median follow-up of 52 months. With a cut-off value of category ≥ 4, the PRECISE scoring system showed sensitivity, specificity, PPV and NPV for predicting progression on AS of 0.76, 0.89, 0.52 and 0.96, respectively. The AUC was 0.82 (95% CI = 0.74-0.90). Prostate-specific antigen density (PSA-D), Likert lesion score and index lesion size were the only significant baseline predictors of progression (each p < 0.05). CONCLUSION: The PRECISE scoring system showed good overall performance, and the high NPV may help limit the number of follow-up biopsies required in patients on AS. KEY POINTS: • PRECISE scores 1-3 have high NPV which could reduce the need for re-biopsy during active surveillance. • PRECISE scores 4-5 have moderate PPV and should trigger either close monitoring or re-biopsy. • Three baseline predictors (PSA density, lesion size and Likert score) have a significant impact on the progression-free survival (PFS) time.

Temperature changes during laser lithotripsy with Ho:YAG laser and novel Tm-fiber laser: a comparative in-vitro study.

AIM: The aim of this study was to compare the thermal effects of Ho:YAG and Tm-fiber lasers during lithotripsy in an in-vitro model via real-time temperature measurement. METHODS: We compared a Ho:YAG laser (pav up to 100 W, Lumenis, Yokneam, Israel) and a superpulse Tm-fiber laser (SP TFL, pav up to 40 W, NTO IRE-Polus, Fryazino, Russia), both equipped with 200 µm bare-ended fibers. The following settings were used: 0.2 J, 40 Hz (nominal pav 8 W). Power meter FieldMaxII-TO (Coherent, Santa Clara, CA, USA) was used to verify output laser power (pav). Each laser was fired for 60 s in two setups: (1) thermos-insulated (quasi-adiabatic) cuvette; (2) actively irrigated setup with precise flow control (irrigation rates 0, 10, 35 mL/min). RESULTS: Power measurements performed before the test revealed a 10% power drop in Ho:YAG (up to 7.2 ± 0.1 W) and 6.25% power drop in SP TFL (up to 7.5 ± 0.1). At the second step of our experiment, irrigation reduced the respective temperatures in the same manner for both lasers (e.g., at 35 mL/s SP TFL - 1.9 °C; for Ho:YAG laser - 2.8 °C at 60 s). CONCLUSION: SP TFL and Ho:YAG lasers are not different in terms of volume-averaged temperature increase when the same settings are used in both lasers. Local temperature rises may fluctuate to some degree and differ for the two lasers due to varying jet streaming caused by non-uniform heating of the aqueous medium by laser light.

Serial changes in tumour measurements and apparent diffusion coefficients in prostate cancer patients on active surveillance with and without histopathological progression.

OBJECTIVE: To analyse serial changes in MRI-derived tumour measurements and apparent diffusion coefficient (ADC) values in prostate cancer (PCa) patients on active surveillance (AS) with and without histopathological disease progression. METHODS: This study included AS patients with biopsy-proven PCa with a minimum of two consecutive MR examinations and at least one repeat targeted biopsy. Tumour volumes, largest axial two-dimensional (2D) surface areas, and maximum diameters were measured on T2 weighted images (T2WI). ADC values were derived from the whole lesions, 2D areas, and small-volume regions of interest (ROIs) where tumours were most conspicuous. Areas under the ROC curve (AUCs) were calculated for combinations of T2WI and ADC parameters with optimal specificity and sensitivity. RESULTS: 60 patients (30 progressors and 30 non-progressors) were included. In progressors, T2WI-derived tumour volume, 2D surface area, and maximum tumour diameter had a median increase of +99.5%,+55.3%, and +21.7% compared to +29.2%,+8.1%, and +6.9% in non-progressors (p < 0.005 for all). Follow-up whole-volume and small-volume ROIs ADC values were significantly reduced in progressors (-11.7% and -9.5%) compared to non-progressors (-6.1% and -1.6%) (p < 0.05 for both). The combined AUC of a relative increase in maximum tumour diameter by 20% and reduction in small-volume ADC by 10% was 0.67. CONCLUSION: AS patients show significant differences in tumour measurements and ADC values between those with and without histopathological disease progression. ADVANCES IN KNOWLEDGE: This paper proposes specific clinical cut-offs for T2WI-derived maximum tumour diameter (+20%) and small-volume ADC (-10%) to predict histopathological PCa progression on AS and supplement subjective serial MRI assessment.

Promises and Hurdles of Medical Tourism Development in the Russian Federation.

Background: Development of medical tourism improves access to healthcare in countries where the necessary medical procedures are not available or accessible to its citizens. In the country of destination, medical tourism stimulates economic development and raises the quality of healthcare provided. There are both microeconomic and macroeconomic factors affecting the development of medical tourism. Microeconomic factors relate to the receivers and providers of healthcare. Macroeconomic factors relate to the government policy being implemented to support the development of medical tourism. This study aims to identify factors affecting the development of medical tourism in Russia. Methodology: An expert survey of 36 heads of medical organizations in Russia was conducted to assess the problems that impede the development of the medical care system to foreign patients in Russia, as well as propose possible solutions. The degree of covariation among experts was calculated using the Kendall concordance coefficient. Results: The experts gave consistent evaluation to numerous sets of problems that impede the development and proposed concrete measures for the development of inbound medical tourism in Russia. These measures ranged from microeconomic to macroeconomic approaches and were directed toward a holistic and coordinated development of medical tourism within Russia. Conclusion: Based on the results, Russia has several micro- and macroeconomic competitive advantages and disadvantages in facilitating medical tourism. The study yielded a set of measures for the development of inbound medical tourism and the promotion of the export of medical services in the Russian Federation, which can be extended to other countries or parties who are seeking to develop medical tourism.

The effect of capped biparametric magnetic resonance imaging slots on weekly prostate cancer imaging workload.

OBJECTIVE: To introduce capped biparametric (bp) MRI slots for follow-up imaging of prostate cancer patients enrolled in active surveillance (AS) and evaluate the effect on weekly variation in the number of AS cases and total MRI workload. METHODS: Three 20 min bpMRI AS slots on two separate days were introduced at Addenbrooke's Hospital, Cambridge. The weekly numbers of total prostate MRIs and AS cases recorded 15 months before and after the change (Groups 1 and 2, respectively). An intergroup variation in the weekly scan numbers was assessed using the coefficient of variance (CV) and mean absolute deviation; the Mann-Whitney U test was used for an intergroup comparison of the latter. RESULTS: In AS patients, a shift from considerable to moderate variation in weekly scan numbers was observed between the two groups (CV, 51.7 and 26.8%, respectively); mean absolute deviation of AS scans also demonstrated a significant decrease in Group 2 (1.28 vs 2.58 in Group 1; p < 0.001). No significant changes in the variation in total prostate MRIs were observed, despite a 10% increased workload in Group 2. CONCLUSION: A significant reduction in weekly variation of AS cases was demonstrated following the introduction of capped bpMRI slots, which can be used for more accurate long-term planning of MRI workload. ADVANCES IN KNOWLEDGE: The paper illustrates the potential of introducing capped AS MRI slots using a bp protocol to reduce weekly variation in demand and allow for optimising workflow, which will be increasingly important as the demands on radiology departments increase worldwide.

Genetic analysis of melanocortin 1 receptor red hair color variants in a Russian population of Eastern Siberia.

The melanocortin 1 receptor is a Gs protein-coupled receptor implicated in melanogenesis regulation. The receptor gene is highly polymorphic, which accounts for the association of several of its single-nucleotide polymorphisms (SNPs) with an increased risk of melanoma. The present study aimed to evaluate the distribution of melanocortin 1 receptor gene variants R151C, R160W, and D294H within the Russian population of Eastern Siberia and its association with melanoma development. Melanoma patients (n=95) admitted to Krasnoyarsk Territorial Oncological Center and healthy controls (n=334) were enrolled in the study. A clinical examination of patients was performed to evaluate the phenotypic features of melanoma patients. SNPs were analyzed by real-time PCR. Clinical examination indicated a more frequent occurrence of fair skin type, blue eyes, blonde and red hair, and more frequent localization of freckles on the neck, trunk, and extremities in the melanoma group of patients. The R151C melanocortin 1 receptor gene variant was found in 18% of melanoma patients and associated with an increased likelihood of melanoma development (odds ratio=6.4; 95% confidence interval: 2.8-14.3; P=0.0001). The two remaining variant alleles of the melanocortin 1 receptor gene occurred with low frequency both in controls and in the melanoma group. The R160W SNP was identified neither in controls nor in melanoma patients. The D294H heterozygous variant was observed in 0.3% of individuals in the control group and in 1.1% of the patients in the melanoma group. Such an asymmetric distribution of the melanocortin 1 receptor within red hair color genotypes in the population under study compared with other populations may be because of Russian genetic homogeneity. Carriers of the mutant R151C allele should exercise caution in terms of exposure to the sun to avoid the risk of melanoma development.