End Of Treatment Course Research Articles

NOVEMA® NIGHT (diphenhydramine + naproxen) in patients with pain and insomnia: results of a multicenter non-interventional observational study

Pain and sleep disorders are interrelated problems that significantly affect patients’ quality of life (QoL) and daily functioning.Objective: to evaluate the efficacy and safety of the use of the combination of diphenhydramine + naproxen (NOVEMA® NIGHT) in patients with acute pain syndrome or exacerbation of chronic pain syndrome and sleep disorders.Material and methods. The study included 4365 outpatients with acute pain (musculoskeletal pain, post-traumatic pain, headache) and sleep disorders who took naproxen 275 mg, 1 tablet in the morning and diphenhydramine 25 mg + naproxen 220 mg (NOVEMA® NIGHT) for 5 days before bedtime. Pain intensity, using a visual analogue scale (VAS), and sleep disorders were assessed before and after treatment; QoL was assessed after treatment using a five-point scale.Results. During treatment, a reduction or complete regression of pain was observed in 92% of cases (60 [50; 61] points on the VAS before treatment versus 10 [0; 20] after treatment; p<0.0001) and normalisation of sleep in most patients: faster falling asleep – in 81% (χ2=9650.2; p<0.0001), an increase in total sleep duration – in 75.5% (χ2=7351.2; p<0.0001), a decrease in the number of nocturnal awakenings – in 84% of patients (χ2=10,568; p<0.0001). At the end of treatment course, the majority of patients rated their quality of life as 4 out of 5 possible points (4 [4; 5]): 41% of patients – “high quality of life”; 48% – “above average”; 11% – “average”; 0.09% – “below average”). None of the patients had a low QoL. The therapy was well tolerated and no patient discontinued treatment due to adverse events (AEs).Conclusion. Short-term treatment (5 days) with naproxen 275 mg and a combination of diphenhydramine 25 mg + naproxen 220 mg (NOVEMA® NIGHT) at bedtime effectively reduces the pain syndrome associated with insomnia. This therapy significantly improves patients’ QoL and has a low risk of AEs, so that we can recommend NOVEMA® NIGHT as an additional analgesic for patients with concomitant sleep disorders.

Brain-derived neutrophic factor, glutamate and markers of apoptosis in the blood of patients with prolonged disorders of consciousness

Aim of the work was to analyze the content of factors with neuroprotective, neurotoxic and apoptotic eff ects in the blood of patients with prolonged disorders of consciousness (pDOC), depending on the level of consciousness disorder and neuroprotective therapy.Material and methods. Research included 53 patients with pDOC, who were divided into 2 groups. Group 1 included 19 vegetative state/unresponsive wakefulness syndrome (VS/UWS) patients, group 2–34 minimally conscious state (MCS “minus” and “plus”) patients. Firstly at admission and then at the end of treatment course (after 1 month on average), plasma concentrations of brain neurotrophic factor (BDNF), apoptosis antigen (APO-1), apoptosisinducing ligand (Fas-L) and glutamate were studied. Control group consisted of 16 patients without measured once.Results. Decrease of BDNF serum level was revealed in patients with pDOC,which was less pronounced those who had TBI as a etiological factor of pDOC. BDNF level signifi cantly increased after a month against the background of neuroprotective therapy. Glutamate level was higher in the fi rst group (VS/UWS). No signifi cant diff erence in the content of apoptosis factors was observed.Conclusion. In patients with pDOC, decrease serum BDNF level was observed, less pronounced in TBI as etiology of pDOC. In patients who matched MCS criteria at the admission, there was a signifi cant increase of BDNF serum level during treatment course, which could indicate that patients with a higher initial level of consciousness have better potential for realizing the eff ect of neuroprotective therapy. Levels of apoptosis factors did not correspond to the consciousness level.

S183 Infusion of Bezlotoxumab at the End of an Antibiotic Treatment Course for Prevention of Recurrent Clostridioides difficile Infection

Introduction: Clostridioides difficile infection (CDI) is the leading cause of infectious diarrhea in the western world. Despite proper antibiotic treatment, recurrence is common, occurring in 25% of patients after first infection. The risk of recurrence increases with each subsequent episode. Bezlotoxumab is a monoclonal antibody given as adjuvant therapy directed against CD toxin B. The proposed mechanism is that it enters the intestinal lumen through damaged gap junctions and prevents recurrence by neutralizing toxin B produced by residual CD spores which germinate after cessation of antibiotics. In the MODIFY I/II trials, Bezlotoxumab reduced recurrent CDI (rCDI) in comparison to placebo by 10%. Moreover, sustained clinical cure at 12 weeks was achieved with Bezlotoxumab in 64% of subjects as compared to 54% of placebo-arm subjects. While timing of Bezlotoxumab administration was studied during the MODIFY I/II trial, there is a paucity of data regarding the timing of infusion in real world scenarios. Methods: We performed a retrospective study of CDI cases at an academic community hospital in a tri-county area. Inclusion criteria included at least one prior rCDI, defined as CDI within less than three months of resolution of a prior episode, and having received infusion of Bezlotoxumab within 48 hours of final dose of antibiotic for rCDI. For these patients, metrics reviewed include whether rCDI occurred following Bezlotoxumab, patient characteristics including medical co-morbidities, and overall medical risk as denoted by Charlson Comorbidity Index. Results: Six patients fit inclusion criteria. 5/6 patients did not experience rCDI following Bezlotoxumab infusion (Table 1). Patient 5 had underlying Ulcerative Colitis and developed rCDI 11 days after Bezlotoxumab but was then cured after 2 fecal microbiota transplant procedures. 4/5 patients whose CDI resolved experienced a self-limited diarrhea episode within 14 days of infusion that resolved without additional intervention. Conclusion: Infusion of Bezlotoxumab near the end of antibiotic therapy appears to be effective for prevention of rCDI in a real-world setting, and thus provides a simple regimen for treatment. We hypothesize that administration of Bezlotoxumab at the end of a treatment course maximizes its efficacy by ensuring a high antibody titer during the period of high risk for rCDI. Future studies should include higher number of patients and direct comparisons against patients receiving Bezlotoxumab earlier in CDI therapy.Table 1.: Patient Demographics and CDI Recurrence after Bezlotoxumab.

Tumour motion analysis from planning to end of treatment course for a large cohort of peripheral lung SBRT targets

Background The aim is to quantify and analyse tumour motion during a course of treatment for lung SBRT patients. Material and methods Peak-to-peak motion of 483 tumours in 441 patients treated with peripheral lung SBRT at a single institution over a two year period was measured on planning CT and at all treatment fractions. Planning 4D-CT scans were analysed using our clinical workflow involving deformable propagation of the delineated target to all phases. Similarly, acquisition of the 4D-CBCT data followed the clinical workflow based on XVI 5.0 available on Elekta linacs. Differences and correlations of the peak-to-peak motion on the planning CT and at treatment were analysed. Results On the planning CT, a total of 81.4% of the tumours had a peak-to-peak motion <10 mm, and 96.1% had <20 mm. The largest motion was observed in the CC direction, with largest amplitude for tumours located in the caudal posterior part of the lung. The difference in amplitude in CC between planning CT and first fraction had a mean and standard deviation of 0.3 mm and 3.5 mm, respectively, and the largest differences were observed in the caudal posterior part of the lung. Patients with a difference in tumour motion amplitude exceeding two standard deviations (>7 mm) at the first fraction were evaluated individually, and they all had poor 4DCT image quality. The difference between the first and second/third fractions had a mean and standard deviation of 0.4 mm/0.5 mm and 2.0 mm/1.9 mm. Conclusion Tumour motion at first treatment was similar to motion at planning, and motion at subsequent treatments was very similar to motion at first treatment. Large tumour motions are located towards the caudal posterior tumour locations. Patients with poor 4D-CT image quality should be closely followed at the first treatment to verify the motion.

Fetal Hemoglobin (HbF) Induction during Initial Decitabine (DAC) Treatment of Elderly High-Risk MDS and AML Patients: A Potential Dynamic Biomarker for Outcome

Introduction:The full effects of DNA-hypomethylating agent (HMA) treatment, the present standard for many MDS and AML patients, often become apparent only after 4-6 months, and only about half the patients eventually respond. Early indicators for subsequent hematologic response to HMAs are as yet very scarce, and urgently needed for better treatment tailoring. HbF is among the potential novel outcome predictors for epigenetic treatments, being induced in vitro and in vivo by HMAs and HDAC inhibitors (Press et al., Leuk. Lymph. 2017); recently, we could demonstrate that HbF elevated prior to HMA treatment was associated with superior outcome of MDS/AML patients (Lübbert et al., Br. J. Haematol. 2017). Therefore, we now asked whether early induction of HbF during treatment with DAC also had predictive value for subsequent outcome of these patients.Patients and Methods:16 MDS and 37 AML patients enrolled on two clinical trials, the 06011 EORTC-GMDSSG phase III trial of higher-risk MDS, and the 00331 phase II trial of older, non-fit AML patients, were treated with DAC. MDS patients received nine 4-hour infusions of 15 mg/m2 given over 72 hours, repeated every 6 weeks for a minimum of four courses. AML patients were treated with nine 3-hour infusions of 15 mg/m2 given over 72 hours, repeated every 6 weeks for four courses followed by maintenance treatment with DAC at 20 mg/m2 when responding (defined by CR, PR or an antileukemic effect). HbF levels were measured in peripheral blood erythrocytes by HPLC before treatment and sequentially, i. e. after the end of each treatment course (every 6 weeks). HbF levels of 0 - 1.0% of total hemoglobin are the normal range in adults, thus HbF > 1.0% was considered induced.Results:HbF measurements at the end of the 2nd DAC treatment course (the first on-treatment time point with consistent HbF induction) were available for 32 patients (15/16 with MDS, 17/37 with AML). Compared to the median pre-treatment HbF of 0.8% , we observed overall induction to 1.1% after course 2, and, in patients achieving CR or PR as best overall response, a median HbF of 1.9% (1.9% MDS, 2.0% AML) at this time point compared to 0.8% (1.0% and 0.6%) in patients not attaining CR/PR (p=0.015 via Wilcoxon 2 sample test). Correlation analyses were performed to determine the association of % HbF after DAC course 2 and responses of the different hematopoietic lineages after course 4. For platelet counts, Spearman's correlation coefficient rs was 0.49 (p=0.01); for neutrophils, rs=0.35 (p=0.08); for Hb, rs=0.36 (p=0.08); for % bone marrow blasts, rs=-0.48 (p=0.03). In patients achieving platelet doubling already after 1 course of DAC, median HbF after course 2 was 1.9%, vs. 0.8% in patients without this platelet response (p=0.006). For MDS patients with induced vs. normal HbF after DAC course 2, median overall survival (OS) from end of treatment course 2 was 22.9 vs. 7.3 months (hazard ratio [HR] 0.21 [CI 0.05 - 0.87], p=0.03), progression-free survival was 7.7 vs. 2.4 months (HR 0.32 [CI 0.10 - 1.10], p=0.07), AML-free survival was 13.1 vs. 7.6 months (HR 0.42 [CI 0.13 - 1.38], p=0.15). For AML patients, median OS from end of course 2 was 20.0 vs. 10.4 months (HR 0.61 [CI 0.21 - 1.75], p=0.35), PFS was not determined. Asking whether clonal cells (derived from the underlying disease) or normal, emerging erythroid precursors synthesize the elevated HbF in response to the HMA, linear regression analyses were performed, which (in conjunction with FISH analyses) strongly suggested that HbF induction observed after 4 treatment courses occurred preferentially in the emerging non-clonal erythroid cells.Conclusions:HbF induction at an early time point during DAC treatment was associated with an early platelet doubling, was predictive for subsequent objective responses and, in MDS patients, for longer survival. Thus determination of HbF induction by this approach may provide a dynamic biomarker during hypomethylating therapy. Particularly in AML, HbF time point optimization appears necessary, and is conducted prospectively within the EORTC trial AML21 (inDACtion vs. induction, NCT02172872) where patients in the experimental arm receive a 10-day course of DAC as initial treatment. DisclosuresClaus:Abbie: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lübbert:Janssen-Cilag: Other: Travel Funding, Research Funding; Ratiopharm: Other: Study drug valproic acid; Celgene: Other: Travel Funding.

Sleeping Sickness: A Cause of False Positive HIV Rapid Diagnostic Tests

RésuméL'approche des mécanismes liés aux résultats faussement positifs des tests de diagnostic rapide (TDR) du VIH chez les patients atteints de la trypanosomose humaine africaine (THA) ou maladie du sommeil contribuera à améliorer la précision du dépistage de l'infection par le VIH, dans les zones endémiques pour la THA.Nous présentons le cas d'une patiente du Congo, prise en charge pour une méningoencéphalite opportuniste d'un sida lors de son admission sur la base d'un TDR VIH qui s'est ensuite révélé faussement positif, et dont le diagnostic était celui de maladie du sommeil. Une étude de cohorte rétrospective réalisée ultérieurement chez des patients atteints de THA, montre que la plupart des TDR VIH positifs avant traitement sont des faux positifs et que la moitié d'entre eux ont disparu à la fin du traitement, ce qui suggère une clearance rapide d'anticorps en réaction croisée avec le parasite.Une part importante des TDR VIH faussement positifs disparaît avant la fin du traitement trypanocide. Là où les tests sérologiques Elisa VIH ne sont pas rapidement accessibles, le renouvellement du TDR VIH en fin de traitement de la THA permet d'identifier environ la moitié des TDR VIH faussement positifs.

Clinical research of postpartum pantalgia treated with individualized moxibustion: 个体化灸法治疗产后身痛的临床研究

ObjectiveTo evaluate the clinical therapeutic effect and safety of individualized moxibustion in treatment of postpartum pantalgia. MethodsA total of 99 patients with postpartum pantalgia were divided into three group at the ratio of 1: 1: 1 according to random number table, i.e. an individualized moxibustion group, a quantitative moxibustion group and a voltaren group. The same acupoints were selected in the individualized moxibustion group and the quantitative moxibustion group. With the patient in supine, Zhōngwăn (中脘CV12),Guānyuán (关元CV4), bilateral Tiānshū (天枢ST25), bilateral Xuèhăi (血海SP10), bilateral Yánglíngquán (阳陵泉GB34), bilateral Zúsānlĭ (足三里ST36) and bilateral Sānyīnjiāo (三阴交SP6) were selected. With the patient in prone, Dàzhuī (大椎GV14), bilateral Géshū (膈俞BL17), bilateral Píshū(脾俞BL20), bilateral Shènshū (肾俞BL23), Mìngmén 命门(GV4), bilateral Wĕizhōng (委中BL40) and bilateral Yŏngquán (涌泉KI1) were selected. In the individualized moxibustion group, the moxibusion dose was determined by patient's constitution and conditions as well as no occurrence of dry throat, thirst and local skin lesion. In the quantitative moxibustion group, the moxibustion dose was fixed as 1 cone at each acupoint in treatment. In these two groups, the treatment was given once every two days, three times a week and the treatment for 2 weeks was as 1 course. Totally, 2 courses of treatment were required. In the voltaren group, voltaren ointment was used externally at the pain area, once a day, for 4 weeks totally. Separately, before treatment, at the end of treatment course and in follow-up, the symptom score of traditional Chinese medicine (TCM), pain score of visual analogue scale (VAS) and patient's treatment satisfaction score were observed in the patients of the three groups. ResultsIn comparison within group, TCM symptom score, VAS score and the treatment satisfaction score at the end of treatment were all reduced obviously as compared with those before treatment in each of the three groups (P < 0.05). In 4, 12 and 24 weeks of followup after treatment, the differences in these data were not significant as compared with those at the end of treatment in the individualized moxibustion group and the quantitative moxibustion group respectively (all P > 0.05). In the voltaren group, these data were not different as compared with those at the end of treatment in 4 weeks of follow-up (all P > 0.05), but these data were all increased as compared with those at the end of treatment in 12 and 24 weeks of follow-up (all P < 0.05). In comparison among three groups, at the end of treatment and in 4, 12 and 24 weeks of followup, the above-mentioned three therapeutic effect indicators were all different significantly (all P < 0.05). In comparison between two groups, in the individualized moxibustion group, TCM symptom score, VAS score and the patient's treatment satisfaction score were all lower than those in the quantitative moxibustion group at the end of treatment and at each time point of follow-up successively, indicating the significant differences (all P < 0.05). ConclusionIndividualized moxibustion and quantitative moxibustion improve the short-term and long-term therapeutic effect on postpartum pantalgia as compared with the external application of voltaren ointment. The therapeutic effect and patient's satisfaction of individualized moxibustion for replenishing kidney and nourishing blood are better than the quantitative moxibustion. The individualized moxibustion therapy for replenishing kidney and nourishing blood achieves a satisfactory effect on postpartum pantalgia and is excelled to voltaren ointment that is strongly recommended in modern medicine. Individualized moxibustion is an external therapy of TCM with optimal short-term and long-term therapeutic effect and reliable safety. Hence, it deserves to be promoted in practice.

Outcome of Sublingual Immunotherapy in Allergic Rhinitis.

Allergic rhinitis (AR) is one of the most common types of allergy worldwide. It has significant negative impact on the quality of life (QOL). One of the available causal treatments of AR is allergen specific immunotherapy which remains effective even after the end of treatment course, unlike symptomatic drugs. AR patients aged above five years, allergic to unavoidable allergen like house dust, mite etc., and refractory to maximal pharmacotherapy were included in present study. Patients allergic to avoidable allergen, taking beta-blocker medication, having other immunological disease, and who were pregnant, breast-feeding or lost to follow up, were excluded from the study. All patients included in the study underwent sublingual immunotherapy (SLIT). The impact of treatment is measured by calculating the difference between SNOT-20 score before and after treatment (which is 6months interval). Total 30 patients were studied. Paired-t test calculated value of cumulative score and nasal symptom score are 7.853 and 6.85 respectively. Both are greater than table value of 2.46. So paired-t test shows that SLIT is very much effective in treatment of AR. The present study re-establish the fact that SLIT not only reduces AR symptoms, it also improves the QOL. It has very good patient compliance with minimal side effects.

The impact of radiotherapy on pulp vitality in patients with head and neck cancer: A systematic review

Introduction: Root canal treatment is considered an ideal treatment option instead of dental extraction to prevent the development of osteoradionecrosis in head and neck cancer (HNC) patients postradiotherapy (RT). This systematic review aimed to assess the impact of RT on pulp vitality in HNC patients. Materials and Methods: The databases of MEDLINE and EMBASE were searched from 1946 up to February 2019 for pulp vitality of the teeth of HNC patients (>16 years old) post-RT. Two authors independently completed the review's stages. The results were summarized narratively. The Joanna Briggs Institute critical appraisal tools were used to assess quality of included papers. Results: 1153 studies were identified and only 2 studies were included in data synthesis. In the two studies, the case and control groups were almost similar according to the source of a similar cohort. Both studies identified confounding variables clearly, but they did not explain strategies used to deal with confounding variables. Conclusions: Pulp vitality might be affected with high doses of RT during treatment (>35 Gy) and at the end of treatment course (60–70 Gy).

Effect of moxibustion on clinical symptoms, peripheral inflammatory indexes and T lymphocyte subsets in COVID-19 patients

To explore the therapeutic effect and the mechanism of the adjuvant treatment with moxibustion on coronavirus disease 2019 (COVID-19). A total of 95 patients with COVID-19 were randomly divided into a moxibustion group (45 cases) and a basic treatment group (50 cases). The routine treatment of western medicine was applied in the patients of both groups. In the moxibustion group, on the base of the treatment of western medicine, moxibustion was applied to Dazhui (GV 14), Feishu (BL 13), Qihai (CV 6) and Zusanli (ST 36), once daily and consecutively for 14 days. At the end of treatment courses, clinical symptom scores for cough, asthmatic breathing, chest oppression and short breath, as well as their remission rates were compared between the two groups before and after treatment. Before and after treatment, the white blood cell (WBC) count, the levels of c-reactive protein (CRP) and interleukin-6 (IL-6) and the absolute number of T lymphocyte subsets, i.e. , and of the peripheral blood were compared in the patients between the two groups. The principal component analysis was adopted to analyze the common data extracted from the above 10 clinical indexes variables and comprehensively evaluate the differences in the therapeutic effect of two regimens. The clinical symptom scores were all decreased after treatment in both of the moxibustion group and the basic treatment group as compared with those before treatment (P<0.05). After treatment, the clinical symptom scores of cough, chest oppression and asthmatic breathing in the moxibustion group were lower significantly than those in the basic treatment group (P<0.05) and the remission rates of cough, chest oppression and asthmatic breathing were higher than the basic treatment group (P<0.05). After treatment, WBC count was increased as compared with that before treatment in either group (P<0.05) and the levels of CRP and IL-6 in the moxibustion group were reduced as compared with those before treatment (P<0.05). The reducing range of IL-6 level in the moxibustion group was larger than the basic treatment group (P<0.05). After treatment, the absolute number of , and T lymphocytes was increased as compared with that before treatment in the moxibustion group (P<0.05), and its increase range was larger than the basic treatment group (P<0.05). The difference value was 33.38 for the score of comprehensive evaluation before and after treatment in the moxbustion group, higher obviously than 8.91 in the basic treatment group. On the base of the routine treatment with western medicine, moxibustion therapy supplemented relieves the clinical symptoms, reduces the levels of inflammatory indexes, i.e. IL-6 and CRP as well as improves the absolute number of peripheral T lymphocyte subsets. The clinical therapeutic effect of such regimen with moxibustion supplemented is significantly better than the simple routine treatment of western medicine.

Platelet rich plasma versus extracorporeal shock wave therapy in patients with non-calcific supraspinatous tears

BackgroundTo compare the clinical efficacy of platelet rich plasma (PRP) subacromial injection and extracorporeal shock wave therapy (ESWT) on refractory non-calcific partial thickness supraspinatous tendon tear.ResultsSignificant improvement in all outcome measures achieved in both groups at 4 weeks follow-up period (the end of treatment course) (P< 0.05). At 12 weeks follow-up period, group I, showed significant improvement in all outcome measures compared to baseline and group II; however, in group II, there was no significant difference compared to baseline; moreover, deterioration in the previous improvement was noticed.ConclusionBoth PRP (group I) and ESWT (group II) are effective therapeutic methods in the management of refractory non-calcific partial thickness supraspinatous tendon tear; however, PRP (group I) has better long-term effects on both pain and function.

Preliminary Results Of Treatment Extranodal NK/T-Cell Lymphoma, Nasal Type Stage I-II AT K Hospital

Background: Extranodal NK/T-cell lymphoma, nasal type, is a rare subtype of non-Hodgkin lymphoma, origin from natural killer (NK) cells and T cells. This is a rare, fast-growing and poor prognosis disease. Currently there have been not many studies in Vietnam on this issue. We conduct this research with two objects: to describe characteristics of patients and evaluate premininary results of treatment extranodal NK/T cell lymphoma, nasal type, stage I to II at K hospital. Methods: Retrospective study. From January 2017 to June 2020, we enrolled 26 patients with extranodal NK/T cell lymphoma, nasal type, stage I to II. Patients were treated concurrent chemoradiotherapy with cisplatin, followed by 3 cycles of VIPD adjuvant regimen. Results: Patient characteristics: The average age was 43.2. Male/female ratio was 1.36. The most common symptoms were stuffy of nose 84.6%; runny nose 65.4%. Peripheral lymph nodes observed in 19.2%; 50% with B symptom. Staged I was dominated with 73.1%. Treatment results: Concurrent chemoradiotherapy phase: completed response was 26.9%, partial response 53.8% and progression disease 19.2%. At the end of treatment course, the overall response rate was 73% (including 61.5% completed response and 11.5% partial response), 26.9% cases with disease progression. Toxicity: Leukopenia was the most common toxicity (61.1%). Grade III and IV leukopenia were observed in 18.4%. Conclusions: Concurrent chemoradiotherapy followed by adjuvant VIPD regimen with stage I, II is effective regimen and acceptable toxicity.

Evaluation of the Anti-Leishmanial Effect of Recombinant Clostridium α-Toxin.

BackgroundLeishmaniasis is an infectious disease common in tropical and subtropical regions caused by the genus Leishmania, which is transmitted by the bite of female sandflies. In this study, we evaluate the anti-leishmanial effect of recombinant Clostridium α-toxin protein alone and the combination with glucantime through in vitro and in vivo.Materials and MethodsProduction, expression, and purification of recombinant α-toxin were evaluated by SDS-PAGE and Western blotting techniques. The antileishmanial activities of the purified α-toxin plus and without glucantime were examined in vitro and in vivo.ResultsThe results indicated successful expression of α-toxin as a 48 kDa band on SDS-PAGE and Western blot methods. Also, evaluation of α-toxin IC50 showed the strong fatal effect of it, and glucantime on medium proliferated Leishmania promastigotes at lower concentrations compared with glucantime or α-toxin alone. Moreover, in vivo surveys showed that at the end of treatment courses, the mean of lesion size diminished in glucantime plus α-toxin treated mice versus negative control groups (p < 0.001). Also, there was a significant difference in the parasite burden of the spleen and liver of the control versus the test groups (p < 0.001).ConclusionThe results showed recombinant α-toxin has synergistic effects with glucantime in destroying Leishmania parasites.

Reinforcement learning for optimal scheduling of Glioblastoma treatment with Temozolomide

Background: Glioblastoma multiforme (GBM) is the most frequent primary brain tumor in adults and Temozolomide (TMZ) is an effective chemotherapeutic agent for its treatment. In Silico models of GBM growth provide an appropriate foundation for analysis and comparison of different regimens. We propose a mathematical frame for patient specific design of optimal chemotherapy regimens for GBM patients. Methods: The proposed frame includes online interaction of a virtual GBM with an optimizing agent. Spatiotemporal dynamics of GBM growth and its response to TMZ are simulated with a three dimensional hybrid cellular automaton. Q learning is tailored to the virtual GBM for treatment optimization aimed at minimizing tumor size at the end of treatment course. Q learning consists of a learning agent that interacts with the virtual GBM. System state is affected by the agent decisions and the obtained rewards guide Q learning to the optimal schedule. Results: Computational results confirm that the optimal chemotherapy schedule depends on some patient specific parameters including body weight, tumor size and its position in the brain. Furthermore, the algorithm is used for scheduling 2100 mg of TMZ on a virtual GBM and the obtained schedule is to administer150 mg of TMZ every other day. The obtained schedule is compared to the standard 7/14 regimen and the results show that it is superior to the 7/14 regimen in minimizing tumor size. Conclusion: The proposed frame is an appropriate decision support system for patient specific design of TMZ administration regimens on GBM patients. Also, since the obtained optimal schedule outperforms the standard 7/14 regimen, it is worthy of further clinical testing.

Madopar combined with acupuncture improves motor and non-motor symptoms in Parkinson’s disease patients: A multicenter randomized controlled trial

IntroductionAcupuncture is increasingly used in the treatment for Parkinson’s disease (PD). This multi-center randomized controlled trial investigated the use of acupuncture in conjunction with the western medication Madopar (levodopa and benserazide) to evaluate the effect of integrated therapy on improving motor and non-motor symptoms in PD patients. MethodsSeventy-six PD patients from three hospitals were randomly assigned to a treatment group (acupuncture + Madopar, n = 38) or a control group (Madopar, n = 38) and participated in a 12-week trial (2 four-week treatment courses and a four-week follow-up). The Unified Parkinson's Disease Rating Scale (UPDRS), modified Webster Scale, Parkinson’s Disease Sleep Scale (PDSS) and Self-rating Depression Scale (SDS) were used to record and evaluate the changes in symptoms. SPSS 22.0 software was used for statistical analysis. ResultsThe treatment group showed greater improvement to that of the control group at the end of treatment course and at follow-up. All scales differed at each time point (P < 0.05) except for UPDRSIV and SDS in the control group (P > 0.05). Scores on the modified Webster Scale and SDS were significantly different between the two groups from Week 4 (P < 0.05), as were other scales except for UPDRSII and UPDRSIII from Week 8 (P > 0.05). No serious drug- or acupuncture-related adverse events and complications were recorded. ConclusionsIntegrated therapy showed a greater advantage, with earlier non-motor symptom improvement. This study also indicated that acupuncture had a certain long-term effect.

Evaluation of newer imidazoles in dermatophytosis

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Eberconazole, a newer Imidazole derivative, antimycotic drug. Similarly, sertaconazole and luliconazole are also newer antifungal which all exhibit fungicidal, fungistatic and anti-inflammatory actions. But, sertaconazole in addition have antipruritic effect also.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Randomized, open-labelled, prospective study comprising of 75 patients divided into three equal groups A, B, C of 25 patients each. Group A received eberconazole 1%, Group B received sertaconazole 2% and Group C received luliconazole 1% for twice daily topical application for 4 weeks. Patients were asked to review at 2&lt;sup&gt;nd&lt;/sup&gt; and 4&lt;sup&gt;th&lt;/sup&gt; week to record clinical and mycological cure.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; In this study out of 75, seventy patients completed the complete course of treatment whereas, five patients were not reported for review citing personal reasons. Parameters included are pruritus, erythema, scaling and vesicles in all three groups. In this study, marked relief of pruritus was achieved clinically with eberconazole (72.7%) followed by luliconazole and sertaconazole with 50.0% and 33.3% respectively at 4&lt;sup&gt;th&lt;/sup&gt; week of treatment phase and reduction of scaling was achieved more with eberconazole (90.9%), sertaconazole (87.5%) and luliconazole (83.3%). All three groups of patients showed successful mycological cure by confirming with negative 10% potassium hydroxide examination at the end of treatment course.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Eberconazole 1% cream was better than sertaconazole 2% cream and luliconazole 1% cream in relieving symptoms like pruritus and scaling at the end of treatment phase and follow up.&lt;/p&gt;

Impact of transcutaneous interferential electrical stimulation for management of primary bladder neck dysfunction in children

Several studies have revealed that electrical stimulation is an effective modality for treatment of lower urinary tract (LUT) dysfunction via raising the capacity or compliance of the bladder or maybe by pelvic floor relaxation and reducing detrusor pressure as well. This study aimed to assess the efficacy of transcutaneous interferential (IF) electrical stimulation on LUT symptoms as well as urine flow parameters in children with primary bladder neck dysfunction (PBND). We reviewed the charts of all children with persistent LUT symptoms who underwent IF electrical stimulation between 2010 and 2017. Twenty-three neurologically and anatomically normal children (mean age: 7.7years, range: 5-13) with LUT symptoms were included in this study. Children had different LUT symptoms such as hesitancy, straining, urinary incontinence and constipation with no sufficient response to medical treatment (α -blocker) for at least 6months. IF electrical stimulation was performed for 15 sessions, two times per week. All children were symptomatic and had abnormal urine flow pattern with an electromyographic (EMG) lag time of more than 6s on uroflowmetry with EMG. A voiding chart, uroflowmetry with EMG and kidney and bladder ultrasounds were performed before and after the treatment for all children. Maximum and average urine flow rates, EMG lag time and postvoid residual volume were analyzed. In addition, alpha blocker therapy was continued during IF therapy. Mean maximum and average urine flow rates improved from 14.1 to 7.6-19.7ml/s and 9.5ml/s, respectively, while mean EMG lag time decreased from 11.7 to 5.2s after the treatment (all P<0.05). Also postvoid residual volume decreased significantly from 35.6 to 7.6mlat the end of treatment courses. Pelvic floor EMG lag time, a documented parameter on uroflowmetry with EMG, defined as the time from the start of pelvic floor relaxation during a volitional voiding effort (the first stage of normal voiding) to the start of urine flow. Results showed that IF therapy decreased pelvic floor EMG lag time in children with PBND. In addition, increase in mean maximum and average urine flow rates in our patients indicated that pelvic IF therapy and behavioral modification improved voiding dysfunction in most of the patients and probably decreased bladder neck activity during voiding. Future studies with larger sample size are needed to support this finding. IF therapy appears safe, effective and reproducible in improvement of PBND in children.

Intranasal delivery of M2 macrophage-derived soluble products reduces neuropsychological deficit in patients with cerebrovascular disease: a pilot study

Objective:We assessed the safety and clinical effectiveness of intranasal therapy with M2 macrophage-derived soluble products (M2-SPs) for treating patients with cerebrovascular disease (CVD).Materials and methods:The protocol of the study was registered at www.ClinicalTrails.gov (NCT02957123). The study group comprised 30 patients with chronic CVD. Neurological status was examined before therapy and at 1- and 6-month follow–up. Concentrations of 32 cytokines in the blood serum were evaluated before and 1 month after therapy onset. Neurological assessment was conducted with the following scales: Subjective Assessment of Clinical (neurological) Symptoms (SACS), Hospital Anxiety and Depression Scale (HADS), Functional Mobility Assessment in Eldery Patients (FMA), and Montreal Cognitive Assessment (MoCa).Results:M2-SPs treatment (once daily for 28~30 days) was found to be safe and well tolerated. Neuropsychological improvements showed the amelioration of neurological symptoms, reduction in anxiety and depression levels, improvement in balance and gait ability as well as cognitive functions. Clinical effects could be detected at the end of treatment course and was stable during 6-month follow-up. Blood serum cytokine evaluation demonstrated diminished baseline levels of many cytokines including those with neurotrophic activity (brain-derived neurotrophic factor, BDNF; hepatocyte growth factor, HGF; migration inhibitory factor, MIF). Upon treatment, most pronounced clinical responses were observed in patients with most severe cytokine deficiency and post-therapy normalization of MIF and HGF levels.Conclusion:Intranasal therapy with M2-SPs is safe and according to preliminary data reduces neuropsychological deficit in patients with chronic CVD. The positive effect of M2-SPs treatment seems to be HGF- and MIF-dependent.

Modern Recommendations and Real Clinical Practice: the Results of the SILA Study

Aim . To assess efficacy and safety of single-pill combination (SPC) amlodipine/perindopril and amlodipine/indapamide/perindopril in patients with uncontrolled hypertension (HT) in routine clinical practice. Material and methods . 16144 patients with uncontrolled HT were included into this multicenter observational study. Eventually 6% of patients were excluded owing to violations of protocol. 15193 patients became subjects to the final statistical analysis; they all were prescribed with single-pill combination amlodipine/perindopril or amlodipine/indapamide/perindopril and subsequently purchased these drugs. Study lasted for 3 months; during this time researchers performed office blood pressure (BP) and heart rate measurements on a monthly basis. Additionally, the researchers registered adverse effects and assessed efficacy and safety using 7-point scale. Results. Initially, patients had an average systolic BP of 1 64.2 ± 1 1.4 mm Hg, diastolic BP - 94.8±8.1 mm Hg, and they also had antihypertensive therapy in 85-89% of cases (in different regions). Patients received ACE inhibitors in 50-54% of cases, angiotensin receptor blockers - in 1 9-23%, calcium channel blockers - in 24-31 %, thiazide diuretics - in 29-36%, beta-blockers - in 27-32%. Monotherapy with ACE inhibitors was used in 1 2-18% of patients, and monotherapy with other antihypertensive drugs - in 1 -4%. Mean age was 60.5 years, mean body mass index - 29.3 kg/m 2 , 43% of patients had a very high risk by SCORE scale. Prescribed therapy: SPCs amlodipine/perindopril (54%) and amlodipine/indapamide/ perindopril (46%) in different doses. By the end of treatment course, the following results have been got: 88% of patients achieved target BP levels (92% and 85% among patients who took SPCs amlodipine/perindopril and amlodipine/indapamide/perindopril, respectively). Systolic BP decreased by 36,6±11,4 mm Hg (22.0±5.9%), diastolic BP - by 15.6±8.5 mm Hg (16.0±8.1%), pulse BP decreased by 21.0±11.4 mm Hg (28.8±13.9%). Mean efficacy assessment rate was 6.9±0.37 points out of 7; mean safety assessment rate was 6.9±0.37 points out of 7. Adverse events were recorded in 257 patients, which constituted 1.7% of the entire patients' population. Conclusion. Using SPC amlodipine/perindopril and amlodipine/indapamide/perindopril is associated with fast achievement of the target BP levels among most patients with a small number of adverse effects.

115. Feasibility study for In-Vivo Dosimetry procedure in routine clinical practice

Purpose To present In-Vivo Dosimetry (IVD) results obtained elaborating EPID images by a commercial software. Methods 8474 IVD tests for 386 cancer patients treated with 3DCRT, IMRT and VMAT techniques, were performed using the SOFTDISO software. SOFTDISO uses EPID-images to calculate for each beam (i) the R index, i.e. the ratio between daily reconstructed dose and the planned one at isocenter point and (ii) a γ -like analysis between the reference EPID image and that obtained in a daily fraction. γ -like analysis supplies two indexes: the percentage of points with γ 1 ( γ % ) and the mean γ value, ( γ mean ) . For each test, the pass criteria for the signals (S) agreement Δ S% and distance to agreement Δ d, were: 0.95 ⩽ R ⩽ 1.05, γ % ⩾ 90% and γ mean ⩽ 0.5. Results The results of R ratios, the γ -like analysis and the visual inspection of out of tolerance tests, together with the patient anatomical images, permitted to individuate 2 classes of errors: class-1, due to inadequate standard quality controls and class-2, due to patient morphological changes. Depending on the technique and anatomical site, a maximum of 18% of tests had at least one index out of tolerance level (OTL). Once removed the causes of class-1 errors, all patients (except four lung and two breast cancer patients treated with 3DCRT) presented mean indexes values ( R ¯ , γ ¯ % and γ ¯ mean ) within tolerance at the end of treatment course. Class-2 errors were found in some patients. As an example, the Table reports the results of 1810 tests for prostate and H&N tumours treated with VMAT technique with 163 OTL tests (9%). As regards the workload, it took 20 min for 10 patients per day. Conclusions The IVD procedure with SOFTDISO resulted easily implementable and able to individuate errors with a limited workload.