Lower Treatment Effect Research Articles

Tuberculosis in the Russian Federation: Situation, Challenges and Perspectives

Tuberculosis (TB) is a significant problem of public health both in Russia and abroad. About one third of the world’s population is infected with Mycobacterium tuberculosis. Every year more than 10 million new TB cases are registered in the world, and about 1.7 million people die from TB. In the Russian Federation, due to the measures taken by the Government and health authorities the epidemic TB situation has been noticeably improved since the sharp deterioration in the 90s of the last century. At the same time, the spread of drug-resistant TB and its low treatment effectiveness, the spread of combined HIV and TB infection reduces the effectiveness of anti-tuberculosis interventions. The research conducted by CTRI, the WHO Collaborating Center for TB in the Russian Federation, is aimed at solving such urgent problems as studying latent infection mechanisms, developing new test systems for accelerated diagnostics of drug resistance, clinical approbation and introduction of short effective regimens of chemotherapy, developing new antituberculosis agents. The achieved successes in the study of tuberculosis in the 21st century creates preconditions for eliminating its epidemic both in Russia and the world, though suggesting imminent breakthrough for tuberculosis is a hasty conclusion.

Efficacy characteristics of different therapeutic modalities for locally advanced prostate cancer: a Bayesian network meta-analysis of randomized controlled trials.

Though previous studies have investigated the efficacy characteristics of several different therapeutic modalities for locally advanced prostate cancer (LAPCa) patients, the available results remained unestablished. Therefore, the aim of this meta-analysis was conducted to clarify such differences. The online PubMed, EMBASE and Web of Science were comprehensively searched for relevant studies published before September 1st, 2017, and eventually eleven relevant studies met the inclusion criteria. The hazard odds ratios (HRs) with 95% credible interval (CI) were utilized to evaluate the efficacy characteristics of several different therapeutic modalities for LAPCa patients by Markov chain Monte Carlo methods. Five different therapeutic modalities were ultimately enrolled to shed light on the efficacy characteristics for LAPCa patients and seven different clinical outcomes were finally analyzed in this study. The cumulative rank probability of overall survival (OS) or cancer-specific survival (CSS) from best to worst was radiotherapy (RT) + orchiectomy, RT + long-term androgen deprivation therapy (LTADT), RT + short-term androgen deprivation therapy (STADT), LTADT and RT; RT + LTADT, RT + orchiectomy, RT + STADT, LTADT and RT, respectively. Meanwhile, in the terms of progression-free survival (PFS), biochemical failure rate (BFR), disease-free survival (DFS), local progression rate (LPR) and metastasis rate (MR), RT + LTADT as well as RT + STADT had a higher, whereas RT alone or LTADT had a relatively lower treatment effect. All in all, our results indicated that RT + LTADT or RT + orchiectomy was among the best two therapeutic regimens in the prognostic aspects of the patients with LAPCa. Furthermore, in consideration of reducing invasive treatment of eligible patients, RT + LTADT could yield better survival benefit of LAPCa patients, compared with others. In addition, the results of our analysis might provide a reference in the clinical selection. Larger sample sizes of strictly designed randomised controlled trials (RCTs) were wanted to validate our findings.

Factors associated with rectal tumor and their influence on tumor regression grade after neoadjuvant chemoradiotherapy

Aim. To determine relation between localization, grade of invasion and differentiation in rectal tumor and tumor regression grade after neoadjuvant chemoradiation therapy.
 Methods. 88 patients with local advanced rectal cancer (Т2-4N0-2М0) were analyzed: 46 females and 42 males. The average age was 52.4±1.4 years. All patients underwent neoadjuvant chemoradiotherapy. In all groups regardless of tumor localization patients with stage T3 and moderate differentiation grade predominated.
 Results. Complete pathological tumor response of grade 4 (TRG4) was revealed in 13 (14.7%) patients, grade 3 (TRG3) in 34 (38.6%) patients, low treatment effect (tumor response grade 2, TRG2) was registered in 26 (29.5%) patients, and lack of treatment effect (grade 1, TRG1) in 15 (17.2%) patients. Analysis of the data from patients with complete or nearly complete tumor regression (grade 3 and 4) demonstrated that such effect of neoadjuvant treatment was most often observed in patients with tumor localized in rectal lower ampulla (58.6%). Among patients with moderately differentiated adenocarcinomas, patients with tumor response of grade 3 and 4 predominated: 28 (56%) patients. According to invasion grade, in all groups patients with therapeutic response grade 3 and 4 prevailed, but most prominently - in groups of patients with stage T4a and T4b - 58.9%.
 Conclusion. The closer to anus tumor is located, the more significant effect neoadjuvant therapy has; moderate tumor differentiation grade can be considered as a relative predictive factor of tumor regression on preoperative chemoradiation therapy.

Risk factors for adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnant women

Intrahepatic cholestasis of pregnant women (ICPW) is associated with an increased risk of complications of pregnancy. Objective prognostic markers of adverse pregnancy outcomes except for a high level of bile acids (BA) in the mother's blood serum, exceeding 40 μmol/l, do not currently exist. However, the determination of the BA levels is not available in all laboratories, which indicates the need to search for other informative prognostic markers of complications of pregnancy in patients with ICPW. Objective: to determine the risk factors for adverse pregnancy outcomes in ICPW. Materials and methods. A prospective study included 97 pregnant women diagnosed with ICPW. The diagnosis was established with an increase in the serum level of the BA in excess of 10 μmol/l. Patients underwent clinical and laboratory examinations with assessment of biochemical markers of liver damage, antioxidant status (determination of superoxide dismutase, glutathione peroxidase, selenium, zinc level). Biochemical indices and severity of pruritus were assessed at the time of diagnosis of ICPW, after 1 and 2 weeks of treatment with ursodeoxycholic acid (UDCA) at a dose of 500 mg to 2 g per day. In the study of perinatal outcomes, the term of delivery, the method of delivery, the presence of signs of intrauterine fetal hypoxia, the state of the fetus at the time of birth were taken into account. Results of the study. In the observed group of patients, the incidence of preterm birth was 31.9%, intrauterine fetal hypoxia 29.9%, pre-eclampsia 23.7%, the need for a cesarean section due to the development of pregnancy complications arose in 40 (41.2%) cases. The risk factors for complications of pregnancy in patients with ICPW were: early onset and longer duration of ICPW, reactivation of cholestasis after its regression against the background of UDCA treatment and less effective treatment of skin itching in patients with manifest forms of ICPW. The laboratory markers of adverse pregnancy outcomes were a high level of maternal total serum BA and a low efficiency of its reduction against the background of treatment, a slow rate of decrease in hepatic transaminase activity against the background of treatment, a low level of antioxidant protection enzymes. The use of sex hormones during pregnancy promoted more frequent development of preeclampsia and increased the frequency of indications for cesarean delivery. The conclusion. Patients with early manifestation of ICPW and reactivation of cholestasis after its regression on the background of treatment, low effectiveness of treatment of pruritus, and also taking drugs of sex hormones require special attention and active management in connection with an increased risk of complications of pregnancy. It is advisable to carry out dynamic monitoring of the level of BA, hepatic transaminases and antioxidant enzymes in dynamics against the backdrop of treatment with ICPW to assess the effectiveness of treatment and timely prediction of possible complications of pregnancy.

Is there association between characteristics of gastric tumor growth and activation of different growth factor systems?

29 Background: Signet-ring cell carcinoma of the stomach (SRCC) is significantly associated with poor prognosis and low treatment effectiveness, compared to adenocarcinoma of the stomach (AC). One of the causes of SRCC aggressive course can be its diffuse invasive growth pattern. The ability of tumor cells to synthesize and/or capture growth factors ensures the independent tumor development. VEGF, EGF, IGFI and EGFII facilitate neoangiogenesis and regulation of malignant processes in paracrine/autocrine mechanisms. The purpose of the study was to find the difference between local levels of VEGF, EGF, IGFI and IGFII in tumor and intact tissues in AC and SRCC. Methods: Levels of VEGF, EGF, EGFR, IGF-I and IGFII were determined by ELISA in tumor and intact gastric tissues of 15 AC patients and 10 SRCC patients (T2-3N0-2M0, G2-3), mean age 62.8±2.38 years. Results: Levels of IGF-I, IGF-II and VEGF in intact gastric tissues were similar in AC and SRCC. EGF and EGFR levels in AC were 2.9 and 1.5 higher than in SRCC. Levels of VEGF in AC tumor tissues, compared to intact gastric tissues, increased by 2.3 times, EGF and EGFR did not change, and IGFI and IGFII decreased by 2.1 and 1.8 times, respectively. Tumor tissues of SRCC patients showed the increased levels of EGF (by 2.9 times) and EGFR (by 1.8 times); VEGF and IGF were similar to the levels in intact tissues. SRCC was characterized by the activation of systems of EGF and IGF, but not VEGF. AC demonstrated the stimulation of VEGFA neoangiogenesis. Conclusions: The activation of systems of EGF and IGF in SRCC could be associated with some characteristics of the diffuse growth pattern and the tumor origin from neuroendocrine cells which facilitates the autocrine/paracrine regulation of the invasive growth. AC requires neoangiogenesis which is realized primarily by the VEGF system.

Randomised controlled trial of Lactobacillus rhamnosus (LGG) versus placebo in children presenting to the emergency department with acute gastroenteritis: the PECARN probiotic study protocol

IntroductionAcute gastroenteritis (AGE) is a common and burdensome condition that affects millions of children worldwide each year. Currently available strategies are limited to symptomatic management, treatment and prevention of dehydration...

The use of nemabiome metabarcoding to explore gastro-intestinal nematode species diversity and anthelmintic treatment effectiveness in beef calves

Next-generation deep amplicon sequencing, or metabarcoding, has revolutionized the study of microbial communities in humans, animals and the environment. However, such approaches have yet to be applied to parasitic helminth communities. We recently described the first example of such a method – nemabiome sequencing – based on deep-amplicon sequencing of internal transcribed spacer 2 (ITS-2) rDNA, and validated its ability to quantitatively assess the species composition of cattle gastro-intestinal nematode (GIN) communities. Here, we present the first application of this approach to explore GIN species diversity and the impact of anthelmintic drug treatments. First, we investigated GIN species diversity in cow-calf beef cattle herds in several different regions, using coproculture derived L3s. A screen of 50 Canadian beef herds revealed parasite species diversity to be low overall. The majority of parasite communities were comprised of just two species; Ostertagia ostertagi and Cooperia oncophora. Cooperia punctata was present at much lower levels overall, but nevertheless comprised a substantive part of the parasite community of several herds in eastern Canada. In contrast, nemabiome sequencing revealed higher GIN species diversity in beef calves sampled from central/south-eastern USA and Sao Paulo State, Brazil. In these regions C. punctata predominated in most herds with Haemonchus placei predominating in a few cases. Ostertagia ostertagi and C. oncophora were relatively minor species in these regions in contrast to the Canadian herds. We also examined the impact of routine macrocyclic lactone pour-on treatments on GIN communities in the Canadian beef herds. Low treatment effectiveness was observed in many cases, and nemabiome sequencing revealed an overall increase in the proportion of Cooperia spp. relative to O. ostertagi post-treatment. This work demonstrates the power of nemabiome metabarcoding to provide a detailed picture of GIN parasite community structure in large sample sets and illustrates its potential use in research, diagnostics and surveillance.

Cognitive behavioral therapy added to pharmacotherapy in patients suffering from pharmacoresistant obsessive-compulsive disorder

BackgroundThe objective of investigation was to determine whether patients with obsessive-compulsive disorder (OCD) resistant to drug therapy may improve their condition using intensive, systematic cognitive behavioural therapy (CBT) lasting six weeks and whether it is possible to predict treatment outcome using clinical and selected psychological characteristics.MethodFrom 66 OCD patients fifty-seven completed program. The diagnosis was confirmed using the structured mini international neuropsychiatric Interview. Patients were rated using the objective and subjective forms of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), objective and subjective forms of the Clinical Global Impression (CGI), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), dissociative experiences scale, 20-item Somatoform dissociation questionnaire and sheehan disability scale before treatment, and with subjective Y-BOCS, objective and subjective CGI, BAI and BDI at the end of treatment. Patients were treated with antidepressants and daily intensive group CBT for six weeks.ResultsDuring 6-week intensive CBT program in combination with pharmacotherapy, there was significant improvement in patients suffering from OCD resistant to drug treatment. There were statistically significantly decreased scores of scales assessing severity of OCD symptoms, anxiety, and depressive feelings. A lower treatment effect was achieved specifically in patients who (a) showed fewer OCD themes in symptomatology, (b) showed higher level of somatoform dissociation, (c) had poor insight and (d) had a higher initial level of overall severity of the disorder. Remission of the disorder was more likely in patients who (a) had good insight, (b) had a lower initial level of anxiety and (c) had no comorbid depressive disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Does entrepreneurship pay for women and immigrants? A 30 year assessment of the socio-economic impact of entrepreneurial activity in Germany

Using data from the German Socio-Economic Panel from 1984 to 2012, we explore income effects of self-employment for females and migrants. Controlling for the selection into self-employment, we differentiate the overall earnings differential between the self-employed and the wage-employed into an endowment effect (they are equipped with characteristics that positively affect earnings in either occupation) and a treatment effect (the income effect solely due to the decision for self-employment). We find that women exhibit both a lower treatment effect and a lower endowment effect than men. Migrants benefit much more from entrepreneurial activities than Germans, having a significantly higher treatment effect. Among the countries of origin, Turkish migrants benefit the most from their self-employment decision, while southern Europeans exhibit the lowest income relevant skills.

Surgical treatment for pulmonary aspergilloma - early and long-term results.

IntroductionPulmonary aspergilloma is a difficult therapeutic problem due to the low effectiveness of conservative treatment and high surgical morbidity.AimTo analyze the early and late results of surgical treatment for pulmonary aspergilloma.Material and methodsFrom 2005 to 2015, 49 patients were treated surgically for pulmonary aspergilloma. Symptoms occurred in 85.7% of cases, including recurrent hemoptysis in 53%. A history of immunosuppressive therapy or chemotherapy was noted in 24.5% of patients. Complex aspergilloma was diagnosed in 79.6% of cases. Immunological test results were positive in 10.2%, and bronchoalveolar lavage samples were positive for Aspergillus species in 18.5% of cases. In 59.2% of patients, the surgical risk was assessed as ASA 3. Thirty seven patients underwent lobectomy, 3 – pneumonectomy, 7 – wedge resection, 1 – decortication, and 1 – cavernostomy.ResultsIn-hospital mortality was 4.1%. Postoperative complications occurred in 63.3% of patients. The most common complications were: prolonged air leak (26.3%), arrhythmias (20.4%), residual pneumothorax (16.3%), respiratory failure (14.3%), atelectasis (12.3%), and bleeding (12.3%). Of the three patients that underwent pneumonectomy, one died, two required repeat thoracotomy because of bleeding, and all three required prolonged mechanical ventilation. Two patients died during the follow-up period. Aspergilloma did not recur in any of the patients who underwent pulmonary resection.ConclusionsDue to the high risk of complications, surgical treatment of pulmonary aspergilloma should be restricted to symptomatic patients in whom lobectomy can be performed. The long-term results of surgical treatment are good, preoperative symptoms abate in most patients, and the rate of aspergillosis recurrence is very low.

Combined chemohormonalradiation treatment of highand very-high-risk non-metastatic prostate cancer

Introduction . Treatment of highand very-high-risk prostate cancer appears to be extremely difficult. External beam radiation therapy combined with long-term androgen deprivation therapy (ADT) plays the main role, though low treatment effectiveness compared to one of intermediateand low-risk groups pushes towards finding new treatment options and modalities. Objective : to enlighten data from modern publications and reviews concerning combined treatment uncluding (or not) chemotherapy and different types of radiation therapy. Risk stratification . Several organizations (NCCN, NICE, ESMO, AUA, EAU and others) offer risk stratification systems. The NCCN system includes the very-high-risk group (Т3b–T4). Nowadays high-risk is set (EAU) when stages ≥ T2c or prostatic specific antigen > 20 ng/ml or Gleason score 8–10 appear. External beam radiation therapy . Recommended dose is ≥ 74 Gy not depending on risk group. Low overall 10-years survival rate makes searching for new effective treatments inevitable. ADT. Long-term regimens (2–3 years) of ADT in high-risk prostate cancer is undoubtable and neccecary. Biochemical progression-free survival can be achieved by using luteinizing hormone-releasing hormone antagonists in long-term regimens. Brachytherapy . Brachytherapy alone and its combination with external beam radiation therapy show high effectiveness concerning progressionfree survival. In high-risk group survival rates are significantly lower. Improvement can be achieved by using adjuvant long-term ADT and other systemic therapy. Nowadays the results of such clinical trials are not available. Chemotherapy . Chemotherapy as part of combination treatment of non-metastatic hormonal-sensitive high-risk prostate cancer is proved to be effective (increasing progression-free and overall survival), but still rarely used treatment option. Conclusion . Reviews, meta-analyses and phase III clinical trials results show improvement of progression-free survival (and some – overall survival) when using a multimodal approach with chemotherapy. Combination treatment of taxane-base chemotherapy, luteinizing hormonereleasing hormone antagonists as ADT and brachytherapy alone or with external beam radiation therapy seems to be extremely perspective and needing further investigation.

La adherencia al tratamiento es siempre peor de lo que cada uno pensamos. Un problema a resolver en la enfermedad inflamatoria intestinal

New diagnostic and treatment tools are the “stars” of scientific meetings but other aspects may have an even greater impact on patients’ lives. Several new studies presented at DDW (Digestive Disease Week) 2016 demonstrated that: a) treatment adherence continues to be suboptimal even in the most advanced health systems; b) lack of adherence correlates with low treatment effectiveness, with higher levels of intestinal damage and higher costs; and c) the factor most consistently associated with poor adherence is age (the younger the patient, the poorer the adherence). In any new programme aiming to enhance the quality of inflammatory bowel disease management, a key element should be the inclusion of new patient information and communication systems to increase treatment adherence. The new tools available in the telemedicine era provide an opportunity to improve the care of inflammatory bowel disease, but their success is limited by multiple problems. Overcoming these barriers should be our key goal in the next few years.

Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale.

BackgroundIn both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events.MethodsThe effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery.ResultsThe multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged < = 60 and in patients >70.ConclusionsThe present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification.

Clinical experience with a variety of approaches to complex and preventive treatment of functional ovarian cysts

Prevalence of ovary tumors today varies from 11 to 20% and has tendency for growth. Current methods of conservative treatment of ovarian cysts lead to their regression in 50–55% of cases and do not rule out the likelihood of recurrence. The lack of specific symptoms, upward trend, and possibility of ovarian cysts malignancy, low effectiveness of conservative treatment, the invalidity and inappropriateness surgical procedures dictate the need to find pathogenetic methods of correction, and this was the aim of the presented work. In study shows results of the treatment of four equal groups of patients aged from 18 to 39 years with functional ovarian cysts depending on the treatment program. Group I include 30 women with functional ovarian cysts who received basic treatment. Group II (n = 30) received hormonal monotherapy. Group III included 30 patients, who received special extract of Vitex agnus castus – BNO 1095. Group IV (n = 30) received hormonal therapy + special extract of Vitex agnus castus – BNO 1095 for 6 months. The highest efficiency, proving the feasibility of plant use in gynecologist practice was in the IV group, which approved a comprehensive treatment program and preventive therapy (hormone + extract BNO 1095). 93.3% women in this group noted almost complete disappearance of pain sensation, normalization of ovarian-menstrual cycle – 83.3%, cystic lesion regression to the size of the follicle –76.6%. Functional ovarian cysts recurrence during the year is not observed only in this group. Special extract of Vitex agnus castus – BNO 1095 is effective in both monotherapy and especially when you turn it into a comprehensive scheme for the treatment and prevention of functional ovarian cysts.

BLOCK HF: how far does it extend indications for cardiac resynchronization therapy?

The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) trial, published in April 2013 [Curtis AB, Worley SJ, Adamson PB, et al; Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial Investigators. Biventricular pacing for atrioventricular block and systolic dysfunction. N Engl J Med 2013; 368:1585-1593], explored whether cardiac resynchronization therapy (CRT) was superior to conventional pacing in patients with conventional indications for pacing, left ventricular dysfunction and NYHA (New York Heart Association) class I-III. The trial took 8 years and a source of concern is selection bias, because participating centers had an average of two patients enrolled per center, per year. Both the internal and external validity of the trial merit some comments. BLOCK HF showed a relatively low treatment effect of CRT as compared with other CRT trials. As a matter of fact, the absolute risk reduction for death or hospitalization because of heart failure was 4.8%, in a relatively long follow-up, with a number needed to treat (NNT) of 21, much higher than the NNT of other CRT trials. We estimate that at least one third of patients in BLOCK HF could meet current indications for CRT. Moreover, the study did not consider the additional risks and costs of CRT versus conventional pacing, both having important implications for cost-effectiveness estimates. For these and other reasons, uncertainties arise as to how far BLOCK HF extends current recommendations for CRT and how much it should be implemented in daily clinical practice.

Cognitive behavioral therapy in pharmacoresistant obsessive-compulsive disorder

BackgroundThe aim of the study was to determine whether patients with OCD resistant to drugs may improve using intensive, systematic CBT lasting six weeks and whether it is possible to predict the therapeutic effect using demographic, clinical and psychological characteristics at baseline.MethodThere were 66 patients included in the study. Fifty-seven patients completed the program. The diagnosis was confirmed by a structured interview MINI. Patient were rated before the treatment using Y-BOCS (objective and subjective form), CGI (objective and subjective form), BAI, BDI, DES (Dissociative Experiences Scale), SDQ 20 (Somatoform Dissociation Questionnaire), and SDS (Sheehan Disability Scale), and at the end of the treatment using subjective Y-BOCS, objective and subjective CGI, BAI, and BDI. Patients were treated with antidepressants and daily intensive group cognitive behavioral therapy for the period of six weeks.ResultsDuring the 6-week intensive cognitive behavioral therapy program in combination with pharmacotherapy, there was a significant improvement in patients suffering from OCD formerly resistant to pharmacotherapy. There were statistically significant decreases in the scales assessing the severity of OCD symptoms, anxiety, and depressive feelings. The lower treatment effect was achieved specifically in patients who:– showed fewer OCD themes in symptomatology;– showed a higher level of somatoform dissociation;– with poor insight;– with a higher level of overall severity of the disorder in the beginning.The remission of the disorder was achieved more probably in patients with:– good insight;– the lower level of initial anxiety;– without comorbidity with the depressive disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Cognitive behavioral therapy in pharmacoresistant obsessive-compulsive disorder.

BackgroundThe aim of the study was to determine whether patients with obsessive–compulsive disorder (OCD) resistant to drug therapy may improve their condition using intensive, systematic cognitive behavioral therapy (CBT) lasting for 6 weeks, and whether it is possible to predict the therapeutic effect using demographic, clinical, and selected psychological characteristics at baseline.MethodsSixty-six OCD patients were included in the study, of which 57 completed the program. The diagnosis was confirmed using the structured Mini International Neuropsychiatric Interview. Patients were rated using the objective and subjective forms of the Yale–Brown Obsessive Compulsive Scale, objective and subjective forms of the Clinical Global Impression, Beck Anxiety Inventory, Beck Depression Inventory, Dissociative Experiences Scale, 20-item Somatoform Dissociation Questionnaire, and the Sheehan Disability Scale before their treatment, and with subjective Yale–Brown Obsessive Compulsive Scale, objective and subjective Clinical Global Impression, Beck Anxiety Inventory, and Beck Depression Inventory at the end of the treatment. Patients were treated with antidepressants and daily intensive group CBT for the 6-week period.ResultsDuring the 6-week intensive CBT program in combination with pharmacotherapy, there was a significant improvement in patients suffering from OCD resistant to drug treatment. There were statistically significantly decrease in the scores assessing the severity of OCD symptoms, anxiety, and depressive feelings. A lower treatment effect was achieved specifically in patients who 1) showed fewer OCD themes in symptomatology, 2) showed a higher level of somatoform dissociation, 3) had poor insight, and 4) had a higher initial level of overall severity of the disorder. Remission of the disorder was more likely in patients who had 1) good insight, 2) a lower initial level of anxiety, and 3) no comorbid depressive disorder.

Interpreting School Choice Treatment Effects: Results and Implications from Computational Experiments

Providing parents and students a choice to attend schools other than their assigned neighborhood school has been a leading theme in recent education reform. To evaluate the effects of such choice-based programs, researchers have taken advantage of the randomization that occurs in student assignment lotteries put in place to deal with oversubscription to popular schools and pilot programs. In this study, I used an agent-based model of the transition to school choice as platform for examining the sensitivity of school choice treatment effects from lottery-based studies to differences in student preferences and program participation rates across hypothetical study populations. I found that districts with higher participation rates had lower treatment effects, even when there were no differences in the distributions of school quality and student preferences between districts. This is because capacity constraints increasingly limited the amount of students who are able to attend the highest quality schools, causing the magnitude of the treatment effect to fall. I discuss the implications of this finding for interpreting the results of lottery-based studies involving choice schools.

Penile Low Intensity Shock Wave Treatment is Able to Shift PDE5i Nonresponders to Responders: A Double-Blind, Sham Controlled Study

We performed sham controlled evaluation of penile low intensity shock wave treatment effect in patients unable to achieve sexual intercourse using PDE5i (phosphodiesterase type 5 inhibitor). This prospective, randomized, double-blind, sham controlled study was done in patients with vasculogenic erectile dysfunction whostopped using PDE5i due to no efficacy. All patients had an erection hardness score of 2 or less with PDE5i. A total of 58 patients were randomized, including 37 treated with low intensity shock waves (12 sessions of 1,500 pulses of 0.09 mJ/mm(2) at 120 shock waves per minute) and 18 treated with a sham probe. In the sham group 16 patients underwent low intensity shock wave treatment 1 month after sham treatment. All patients were evaluated at baseline and 1 month after the end of treatment using validated erectile dysfunction questionnaires and the flow mediated dilatation technique for penile endothelial function. Erectile function was evaluated while patients were receiving PDE5i. In the low intensity shock wave treatment group and the sham group 54.1% and 0% of patients, respectively, achieved erection hard enough for vaginal penetration, that is an EHS (Erection Hardness Score) of 3 (p <0.0001). According to changes in the IIEF-EF (International Index of Erectile Function-Erectile Function) score treatment was effective in 40.5% of men who received low intensity shock wave treatment but in none in the sham group (p = 0.001). Of patients treated with shock waves after sham treatment 56.3% achieved erection hard enough for penetration (p <0.005). Low intensity shock wave treatment is effective even in patients with severe erectile dysfunction who are PDE5i nonresponders. After treatment about half of them were able to achieve erection hard enough for penetration with PDE5i. Longer followup is needed to establish the place of low intensity shock wave treatment in these challenging cases.

Эффективность митоксантрона у больных с прогредиентными типами течения рассеянного склероза

Изучена эффективность, безопасность и переносимость митоксантрона у 67 пациентов с прогредиентными типами течения (ПТТ) рассеянного склероза (РС).Проведен анализ клинико-радиологических данных у 19 больных с первично-прогредиентным (ППТ) и у 48 больных со вторично-прогредиентным течением (ВПТ) РС, получавших цитостатик II ряда — митоксантрон. Оценка клинической и радиологической активности заболевания по результатам лечения проводилась непосредственно после курса приема митоксантрона и ежегодно в течение 2 лет после его окончания. Учитывалась динамика выраженности неврологического дефицита по данным шкалы инвалидизации EDSS, наличие и длительность этапа стабилизации, темпы и варианты дальнейшего прогрессирования, характер прогноза, количество гадолиний-контрастированных повреждений по данным МРТ. С учетом этих показателей были разработаны критерии высокой, умеренной и низкой эффективности лечения. К моменту окончания курса митоксантрона высокая эффективность лечения в виде частичного регресса неврологического дефицита на фоне стабилизации была получена у 25 % больных при ВПТ и у 21,1 % — при ППТ с неопределенным характером прогноза; умеренная эффективность в виде стойкой стабилизации также преобладала у больных с неопределенным характером прогноза — у 50 % при ВПТ и у 36,8 % при ППТ; низкая эффективность в виде замедления темпов неуклонного варианта прогрессирования и его трансформации в более благоприятный поступательный вариант определялась у 22,9 % больных с ВПТ и у 26,3 % с ППТ с неблагоприятным характером прогноза. К моменту окончания двухлетнего катамнестического наблюдения позитивный терапевтический эффект митоксантрона с высокой и умеренной эффективностью сохранялся у 50 % больных при ВПТ и у 42,1 % — с умеренной эффективностью при ППТ. За этот период отрицательная динамика с избирательной реорганизацией показателей эффективности была получена у 20 (41,6 %) больных с ВПТ и у 11 (57,9 %) — с ППТ РС. Митоксантрон, по данным мониторинга МРТ, замедляет радиологическую активность воспалительного процесса, уменьшает число новых подтвержденных гадолиний-контрастируемых очагов поражения, но не оказывает влияния на общий нейродегенеративный процесс, который зависит от длительности, тяжести и типа течения РС с преобладанием при ППТ.Заключение. Доказана клиническая и радиологическая эффективность цитостатика митоксантрона в качестве метода деэскалационной иммуносупрессивной терапии при тяжелых малокурабельных прогредиентных формах РС с учетом типа течения, характера прогноза, степени выраженности неврологического дефицита, темпов и вариантов прогрессирования.