Course Of Combination Therapy Research Articles

Modified Acceptance and Commitment Psychotherapy in Complex Treatment of Comorbidity of Post-traumatic Stress Disorder and Mild Traumatic Brain Injury

The objective: approbation of the effectiveness of modified Acceptance and Commitment Therapy in a complex treatment of patients with comorbidity of posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI). Materials and methods. 329 veterans from three clinical groups: individuals with PTSD (n=109), with mild TBI (n=112) and with comorbid PTSD + TBI (n=108), underwent a course of combined therapy lasting 8 weeks: in addition to standard therapy, they received psychotherapeutic intervention (psychoeducation with elements of motivational interviewing and acceptance and commitment therapy for PTSD) and transcranial direct current stimulation (tDCS). The evaluation of the effectiveness of the treatment, in addition to a comprehensive psychodiagnostic examination before and after the therapy, included the Quality of Life Assessment Scale (O. Chaban). Results. Based on the obtained data, we can assume that representatives of the PTSD group, who initially evaluated the quality of social aspects of their lives more negatively, after the therapy looked more positively at the emotionally colored spheres of life (sex and mood). At the same time, after the therapy, the feeling of satisfaction with life was more positively assessed by those patients who were more satisfied with their life conditions before the therapy, and a higher assessment of the quality of life after the therapy was observed in those patients who, even before the therapy, had a higher level of satisfaction with your sex life. Summarizing the obtained data, it can be asserted that as a result of the therapy, the best results in the direction of increasing self-esteem of the quality of life were achieved precisely in relation to patients with PTSD/TBI. Conclusions. Complex treatment of patients with comorbid PTSD and TBI using modified acceptance and Acceptance and Commitment Therapy in combination of standard treatment and tDCS is a promising individual treatment methodology in this patient population.

A Large-Scale Multicenter Retrospective Study on Nephrotoxicity Associated With Empiric Broad-Spectrum Antibiotics in Critically Ill Patients

Evidence regarding acute kidney injury associated with concomitant administration of vancomycin and piperacillin-tazobactam is conflicting, particularly in patients in the ICU. Does a difference exist in the association between commonly prescribed empiric antibiotics on ICU admission (vancomycin and piperacillin-tazobactam, vancomycin and cefepime, and vancomycin and meropenem) and acute kidney injury? This was a retrospective cohort study using data from the eICU Research Institute, which contains records for ICU stays between 2010 and 2015 across 335 hospitals. Patients were enrolled if they received vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. Patients initially admitted to the ED were included. Patients with hospital stay duration of< 1 h, receiving dialysis, or with missing data were excluded. Acute kidney injury was defined as Kidney Disease: Improving Global Outcomes stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match patients in the control (vancomycin and meropenem or vancomycin and cefepime) and treatment (vancomycin and piperacillin-tazobactam) groups, and ORs were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission. Thirty-five thousand six hundred fifty-four patients met inclusion criteria (vancomycin and piperacillin-tazobactam, n= 27,459; vancomycin and cefepime, n= 6,371; vancomycin and meropenem, n= 1,824). Vancomycin and piperacillin-tazobactam was associated with a higher risk of acute kidney injury and initiation of dialysis when compared with that of both vancomycin and cefepime (Acute kidney injury: OR, 1.37 [95%CI, 1.25-1.49]; dialysis: OR, 1.28 [95%CI, 1.14-1.45]) and vancomycin and meropenem (Acute kidney injury: OR, 1.27 [95%, 1.06-1.52]; dialysis: OR, 1.56 [95%CI, 1.23-2.00]). The odds of acute kidney injury developing was especially pronounced in patients without renal insufficiency receiving a longer duration of vancomycin and piperacillin-tazobactam therapy compared with vancomycin and meropenem therapy. VPT is associated with a higher risk of acute kidney injury than both vancomycin and cefepime and vancomycin and meropenem in patients in the ICU, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider vancomycin and meropenem or vancomycin and cefepime to reduce the risk of nephrotoxicity for patients in the ICU.

Pneumonitis associated with pembrolizumab plus chemotherapy for non-squamous non-small cell lung cancer

Studies elucidating detailed characteristics of pneumonitis in association with chemo-immunotherapy are limited. We aimed to investigate the characteristics of images, prognostic factors, and clinical course of combination therapy associated with pneumonitis. A multicenter, retrospective cohort study of patients with non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed, and pembrolizumab was conducted. Patients with confirmed pneumonitis established by an independent multidisciplinary team were enrolled. For 53 patients with pneumonitis, radiographic features at diagnosis predominantly comprised an organizing pneumonia pattern (62%, 33/53). Twelve (23%) patients experienced a worsening respiratory status during pneumonitis management, which was associated with a high mortality rate (58%, 7/12) during treatment. Severe grade at pneumonitis diagnosis (p < 0.001), diffuse alveolar damage (DAD) pattern (p = 0.002), and disease extent ≥ 25% in the lungs (p = 0.009) were significantly associated with worsening respiratory status. Furthermore, post-diagnosis survival was significantly worse in severe pneumonitis (p = 0.02) than in mild and in patients with the DAD pattern than in those without (p < 0.0001). We showed detailed clinical course of patients with pneumonitis and reported several important influencing factors. Given the small number of trials on pneumonitis, our findings provide valuable information to guide the development of appropriate management guidelines and improve pneumonitis treatment.

Primary malignant melanoma of the esophagus successfully treated with camrelizumab: A case report and literature review*

Abstract An 83-year-old Chinese woman presented with a 3-month history of dysphagia. She also had a history of hypertension, type 2 diabetes, fundus hemorrhage, and cataract but no history of cutaneous, ocular, or other-site melanomas. Upper gastrointestinal tract angiography revealed gastritis and duodenal diverticulum; thus, an endoscopic review was recommended. Enhanced computed tomography of the chest and upper abdomen revealed the following: (1) Esophageal space-occupying lesions and mediastinal lymph node enlargement (considering the high possibility of esophageal cancer, further endoscopy was recommended) and (2) A small amount of right pleural effusion, with no significant lymph node infiltration or distant metastasis. Esophagoscopy identified a bulge mass blocking the esophagus from 23 to 30 cm from the incisors. The upper mass had a spherical clustering, while the lower mass significantly festered. Pathological biopsy samples were obtained from the esophagus 23 and 28 cm from the incisors. Tissue biopsy showed proliferation of large round tumor cells and melanocytes. Immunohistochemistry showed positive findings for HMB45 and MelanA; partially positive findings for S100, CK7, CK5/6, CAM5.2, LCA, P63, and TTF-1; and negative findings for Syn. The Ki-67 positivity index was approximately 60%. Based on these findings, the patient was diagnosed with malignant esophageal melanoma with enlarged mediastinal lymph nodes. She was then treated with five cycles of camrelizumab therapy combined with chemotherapy from October 18, 2019, to May 5, 2020. Gastroscopy review following two courses of combination therapy revealed that the esophagus was 23-25 cm away from the incisors, and there were two continuous uplifted and beaded masses that had a smooth and black surface, with each of them having a length and diameter of approximately 1 cm. Melanosis of the mucosa around the lumen was observed at 40 cm from the incisors to the cardia; the dentate margin was clear; and the cardia had no stenosis. The patient then received five courses of combination therapy and became consistently stable after partial remission. No severe adverse events related to the immunotherapy were recorded. Camrelizumab may be a viable treatment option for patients with PMME. Additional evidence from future clinical trials and research is necessary to fully validate our findings.

Results of complex therapy of the central retinal vein occlusion using laser methods of treatment

Aim to analyze and compare the effectiveness of conservative treatment and complex methods (intravitreal injections of angiogenesis inhibitors and retinal laser coagulation) of the central retinal vein occlusion treatment.&#x0D; Material and methods. Based on the case histories, there were analyzed the results of central retinal vein occlusion treatment in 40 patients (the average age is 63) who were treated at the Republican Ophthalmological Hospital.&#x0D; Results. The course of combined therapy including the anti-VEGF injections and retinal laser coagulation showed the best results: a more significant and persistent decrease of retinal edema and a more marked increase of visual acuity, if compared to conservative therapy of the central retinal vein occlusion.&#x0D; Conclusion. The results obtained allow us to recommend the complex treatment of the central retinal vein occlusion as the best method for fast and persistent elimination of retinal edema, increased visual acuity and prevention of complications.

Опыт оптимизации лечебной помощи женщинам в климактерии с синдромом «сухого глаза»

Purpose. Optimization of medical care for women in menopause with dry eye syndrome from the standpoint of experimental and clinical substantiation of combined technologies. Material and methods. The studies were carried out on a group of 72 patients (144 eyes) in the postmenopausal period with dry eye syndrome. The average age of women was 54.4±3.3 years. All patients, depending on the therapy, were divided into two groups. The first group (control) consisted of 34 women (68 eyes) who received only local daily monotherapy for 20 days – instillation of low-viscosity «artificial tear» preparations HyloComod. Patients of the main group were divided into 2 subgroups and used a combined treatment technology. The first subgroup consisted of 21 patients (42 eyes), who, in addition to local daily therapy of the above drug, received a suis-organ complex preparation of estrogen-like orientation Ovarium compositum once every 3 months. The second subgroup included 17 patients (34 eyes) who received a treatment technology that included local daily therapy with artificial tears in combination with courses (once every 3 months) of exposure to the head area by a pulsed low-frequency electromagnetic field in combination with suis-organ complex preparation of estrogen-like orientation Ovarium compositum. Results. The combined treatment technology was well tolerated in all examined women. There were no complications or side effects. A significant increase in the main tear production in women of the main group made it possible to achieve a significantly more pronounced decrease in symptoms of subjective discomfort than in women in the control group. The achieved results of treatment of women in the main group persisted for 2.5–3 months, which determined the frequency of the courses of combination therapy with a frequency of twice every 6 months during the subsequent observation period. Conclusion. The course of combined therapy makes it possible to achieve significant relief of subjective manifestations of dry eye syndrome in postmenopausal women. The implementation of the therapeutic effect occurs, apparently, due to the synergism of the natural factors used, which makes it possible to significantly activate the compensatory and adaptive processes in the meibomian glands. Key words: dry eye syndrome of climacteric origin, combined treatment technology, estrogen deficiency, sex hormones.

Pain syndrome in adenomyosis. Finding new pathogenesis links and non-hormonal correction opportunities. Literature review

Adenomyosis is characterized by polymorphism of clinical manifestations and is the cause of chronic pelvic pain associated with endometriosis in 53–80% of cases. Heavy dysmenorrhea in adenomyosis is a key factor that reduces the quality of life and, moreover chronic pain reduces stress resistance and launches the rehabilitation cytokines cascade, which causes exacerbation of endometriosis. Formation of painful syndrome with adenomyosis may be due to: changes in neurohumoral regulation, stimulation of nerves and blood vessels growth and myometrium inflammatory remodeling against the background of circulatory disorders and vascular sclerosis. These processes lead to violation of neuroimmune relationships that determine the increase in the number and sensitivity of nociceptors against the background of the chronic immuno-inflammatory process in endometrials and myometry.Experimental studies have shown that the supraspinal role of the nitric oxide (NO) is to indirect mechanical nociceptive reflexes. The dose-dependent L-arginine role in the pain syndrome formation also was shown; it was found that small doses of L-arginine lead to the activation of nNO-synthase and analgesic effect. Large doses are activated by cotorphine synthase to form a dipeptide of cortorphine (L-tyrosine-L-arginine), which induces the met-enkephalin release and analgesic effect. Individual studies have demonstrated a decrease in the symptoms of urinary pain syndrome during L-arginine treatment, which made it possible to include it into the European Association of Urologists recommendations on the chronic pelvic pain treatment in 2017.Clinical comparative study (2013) of the NO donator (L-arginine) effectiveness in the treatment of endometriosis-associated intermenstrual pelvic pain and dysmenorrhea showed a high efficiency of a 3-month course of combination therapy (dienogest 2 mg + Tivortin 4.2 g). Supplement of basic therapy by NO donator (L-аrginine) has shown a faster reaching the clinical effect on reducing endometriosis-associated symptoms and sustainable maintenance of the result achieved. The multifaceted pharmacological effects of L-arginine directly affect a number of essential factors for the adenomyosis development and progression, which allows using this drug in clinical practice.

Study of Side Effects of Patients Receiving Cisplatin in the Treatment of Cervical Cancer by Age Group

Background: Cisplatin is one of the options of chemotherapy used to treat cervical cancer. Patient can experience side effects from drugs frequently with many factors as a catalyst including the age of the patient.&#x0D; Objective: To compare the side effects of cervical cancer patients receiving concurrent chemoradiotherapy (Cisplatin) 2 rounds between patients ≤ 60 years and &gt; 60 years.&#x0D; Methods: A retrospective study, 70 cervical cancer patients undergoing concurrent chemoradiotherapy at Ramathibodi Hospital were investigated. Questionnaires about adverse effects were completed by patients at home 7 days after 1st and 2nd courses of combined therapy. The side effects of cervical cancer patients between groups was analyzed.&#x0D; Results: Of 70 patients, there were 47 patients ≤ 60 years and 23 patients &gt; 60 years. After the 1st course, life-threatening side effects occurred in 9 patient’s ≤ 60 years but none occurred in patients &gt; 60 years. Younger patients also had significant more nausea than older patients (P &lt; .05). After the 2nd course, younger patients also had significant more vomiting than older patients (P &lt; .05). The most common side effects for both age groups were fatigue and anorexia respectively.&#x0D; Conclusions: Patients younger than 60 year would experience significantly more symptoms of nausea and vomiting after the 1st and 2nd courses of concurrent chemoradiotherapy.

Evaluation of a 12-week allopurinol-lowering therapy in combination with the non-steroidal anti-inflammatory drug meloxicam in patients with gout

To evaluate a 12-week course of combined alloturinol-lowering therapy with a prophylactic anti-inflammatory dose of movalis for the frequency of exacerbations and the quality of life of patients with gout. Allopurinol was administered orally, 1 time per day. Every 3 weeks, the dosage of the drug was increased by 50 mg to 300 mg per day under the control of the level of serum uric acid (sUA). The total daily dose of the drug movalis, used in the form of different dosage forms, was 7.515 mg. The clinical effectiveness of the treatment was evaluated after 3, 6, 9 and 12 weeks according to physical examination, the dynamics of joint pain at rest, during movement and palpation, according to the visual analogue scale (VAS) in millimeters, Likert scale, EuroQol-5D-5L questionnaire, care for oneself, habitual daily activities, the presence of anxiety and depression, assessment of satisfaction with treatment (on a scale of 1 to 5, where 1 is the complete absence of improvement or worsening, and 5 is a very good result); took into account the period of remission, as well as the time before the onset of relapse of gouty arthritis. An adverse event (AE) was recorded. On the background of treatment with movalis 7.5 mg per day more than two-thirds of patients showed no worsening of the articular syndrome with an increase in the dose of allopurinol to 300 mg per day. By the 12th week of observation, a significant difference was found between the severity of gouty arthritis characteristics in the direction of improving mobility, self-care, normal daily activities, reducing soreness, reducing anxiety and depression (p0.05). In addition, the ESR and sUA levels were significantly different initially and at the final observation point (p0.05), which indicates a positive effect on the inflammatory process. A 3-month course of combination therapy was not accompanied by significant increases in blood pressure, changes in creatinine clearance in blood serum. There were no adverse events from the gastrointestinal tract. 90.9% of patients rated the treatment result as very good. AE in the form of a skin allergic rash was observed in one patient; it did not require interruption of treatment and completely stopped without consequences after completion of the course. 12 a week-long combined therapy of the allopurinol-reducing drug with the anti-inflammatory dose movalis prevents the exacerbation of the articular syndrome and improves the quality of life of patients with gout.

Abstract 4072: A combinational therapy of oncolytic virus and nature killer cells for melanoma treatment

Abstract Immunotherapy has obtained substantial impact on the clinical treatment of melanoma which is largely resistant to current therapies as chemotherapy and radiotherapy. Oncolytic virotherapy of melanoma is an appealing approach for inducing not only tumor cell death but also antitumor immunity. Furthermore, NK cells, a lineage of innate lymphocytes, not relying on peptides presented in an HLA class I context, have gained more and more attention as anti-melanoma effector cells. However, the combination of oncolytic adenovirus and NK cells has not yet been explored in melanoma. In this study, the combinational efficacies of oncolytic virus H101 and NK cells was tested in vitro. The combination of H101 and NK cells resulted more efficient killing of tumor cells (HT29, A549 and HepG2) compared to the monotherapies, and displayed no significant cytolytic effect of normal cells (HUVEC and MRC-5). In addition, we present a patient with right maxillary sinus malignant melanoma who was treated with the combination of H101 and adoptive NK cells. We observed intratumoral injections of H101 without dose-limiting toxicity. H101 injections stimulated self-immunity response with transient whole body fever. Furthermore, NK injections caused tumor temperature rise although contralateral cheek temperature was normal and body temperature was normal. Data are consistent with the hypothesis that virus-infected cancer cells attracted NK accumulation within tumor. The homing NK cells attacked targeted cancer cells, causing local temperature rise. Two courses of combination therapy in conjunction mediated the significant durable regression of melanoma, which had been ongoing for &amp;gt;22 months, and it represents a new immunotherapy approach for the treatment of these patients. Citation Format: Lin Chen, Xianju Chen, Xiankui Tan, Meng Li, Fang Hu, Haiyan Zhang, Xiaoyuan Wang. A combinational therapy of oncolytic virus and nature killer cells for melanoma treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4072.

Arterial hypertension in young

The aim of the study was to increase the effectiveness of treatment of arterial hypertension (AH) in young people with clinical signs of autonomic dysfunction.Materials and methods. The study included 65 men with hypertension aged 30–40 years (mean age 35.6±4.3 years). In 32.3 % of patients with hypertension was 1 and 67.7 % – 2 degree. The control group consisted of 20 healthy men. All examined individuals were assessed for clinical status, measurement of office BP, daily monitoring of blood pressure. The assessment of autonomic dysfunction was carried out using the questionnaire (A. Vane, 2003). To assess the situational anxiety and personality questionnaire used anxiety Ch. D. Spielberger (1973) in Yu. L. Hanin adaptation. Non-specific changes in the functional state of the central nervous system were assessed by analyzing the heart rate variability on the ECG complex of the Holter monitoring.Results. After treatment, target blood pressure levels were achieved in 23 (76.7 %) patients of the 1st group and 31 (88.6 %) in the second group. Patients with hypertension and clinical signs of autonomic dysfunction, who received complex therapy with the addition of ethyl methyl hydroxypyridine succinate, showed a more pronounced increase in total HRV, decreased activity of the sympathetic part of the autonomic nervous system and the recovery of autonomic balance according to the time of HRV. After a course of combined therapy with the addition etil methylhydroxypyridine succinate was observed marked reduction in the level of reactive anxiety by 41 % (p&lt;0.001) and personal anxiety by 37.8 % (p&lt;0.001), which indicated an improvement in the psycho-emotional state in these patients. Thus, the addition of ethylmethylhydroxypyridine succinate to the complex therapy of young men with hypertension and the clinical signs of autonomic dysfunction has a positive effect on clinical symptoms, contributes to the restoration of the autonomic balance and correction of the psycho-emotional state.

Remission in the Patient with Malignant Pleural Mesothelioma: A Case Report

Here, we report the patient with Stage IV malignant pleural mesothelioma (MPM), who has reached the remission in 5 months of treatment with experimental targeted product (WO/2017/052419). The remission has been confirmed by PET examination performed in German clinic - as the absence of tumor tissue in primary localization and the absence of the distant metastases. Previous patient’s treatment was not successful. Previous treatments included 6 courses of combined chemotherapy consisted of cisplatin, pemetrexed, and bevacizumab; visceral and parietal pleurectomy combined with hyper-thermic intrathoracic chemotherapy (HITHOC); 6 courses of combined therapy with monoclonal antibodies nivolumab and ipilimumab. All that treatments did not demonstrate necessary clinical effect. The therapy with monoclonal antibodies caused also severe side effects- polyarthritis. Due to all these reasons and significant worsening of patient’s general condition and laboratory parameters, the patient according to his freewill decision started treatment with experimental targeted product (WO/2017/052419) as single anti-tumor agent and in 5 months has reached the remission. General condition improved significantly as well. ECOG score changed from 2-3 points at the therapy start to 0-1 point in 5 months of the treatment. The patient fulfils his routine duties in the office.

Influence of Combined Laser and EHF-Irradiation on Correction of Microcirculator Disorders in Inflammatory Diseases of Parodont

Aim - to prove the necessity of including the methods, which normalize the vascular and intravascular component of the hemostasis system, in the combined therapy of inflammatory periodontal diseases, as the microcirculation disorders play the most important role in the pathogenesis of inflammatory periodontal diseases and correlates with severity level. Materials and methods. In order to study the possibility to correct the malformation of the adhesive and aggregation activity of the blood platelets in patients with inflammatory periodontal diseases, we carried out a study of the adhesion and aggregation of platelets after a course of combined therapy, which included combined effects of laser and EHF radiation. The most important link in restoration of microcirculation is the vasoregulative effect of laser irradiation. Results. There is a partial or complete restoration of aggregation and adhesive activity of the blood platelets. Conclusion. The use of combined laser and EHF radiation of the “Matrix” equipment allows stopping the inflammation of the tissues quickly. Correction of these disorders by non-drug methods, in comparison with a medication-assisted treatment, has no side effects, and can be recommended as a component of combined therapy in patients with inflammatory periodontal diseases.

Combined therapy of erectile dysfunction

The objective: evaluation of the efficacy and safety of combination therapy of L-arginine and PDE-5 inhibitors in erectile dysfunction.Materials and methods. The subject of the study was 34 patients with erectile dysfunction aged 20 to 45 years, with the presence of manifestations of erectile dysfunction from mild to moderate severity. Patients took L-arginine daily for 30 days and a day later PDE-5 inhibitors. The criterion of therapeutic effectiveness of the drug was the dynamics of the quality of erection.Results. After the course of combination therapy, 28 patients (82,3%) could have intimate proximity with a sufficient erection, and in 4 (11,7%) patients the erection recovered completely, which indicates the high effectiveness of these drugs.Conclusion. Combined therapy with L-arginine and an inhibitor of PDE-5 type in erectile dysfunction has a positive effect on the severity of erections.

Neuroprotective Therapy of Chronic Cerebral Ischemia in Out-Patient Conditions

Objectives. To conduct a differential analysis of the efficacy of combined treatment using drugs with different mechanisms of action (Mexidol, aescusan, Halidor) in patients with chronic cerebral ischemia (CCI) stages I, II, and III in out-patient conditions. Materials and methods. The study included 50 patients with diagnoses of chronic cerebral ischemia stages I–III of atherosclerotic, hypertensive, and mixed origin (20 patients with stage I, 20 with stage II, and 10 with stage III). On the background of basal treatment, patients received three courses of combined therapy with Mexidol, Halidor, and aescusan for six weeks with three-month intervals between courses. Changes in patients’ subjective complaints and objective clinical signs were evaluated after each course. Results and conclusions. Clinical neurological investigations demonstrated the therapeutic efficacy of prolonged complex treatment with different courses of antioxidants. Use of the combination of Mexidol, aescusan, and Halidor promoted improvements in cognitive, adaptive, and motor functions in patients with CCI stages I and II. Increases in treatment efficacy were obtained in patients with CCI stage III by supplementing the neuroprotective actions of the drugs used with agents improving cognitive functions.

A metabolomics strategy to explore urinary biomarkers and metabolic pathways for assessment of interaction between Danhong injection and low-dose aspirin during their synergistic treatment.

The drug combination of Danhong injection (DHI) and low-dose aspirin (ASA) was frequently applied for the treatment of cardiovascular and cerebrovascular diseases. Due to the drug interactions, a lot of potential benefits and risks might exist side by side in the course of combination therapy. However, there had been no studies of interaction between DHI and ASA. Metabolomics was a powerful tool to explore endogenous biomarkers and metabolic pathways. In present study, metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS) coupled with multivariate statistical analysis was performed to provide insight into understanding the interaction between DHI and low-dose ASA. Eleven potential biomarkers of three types were identified and seven metabolic pathways were constructed. The results showed that the interaction between DHI and low-dose ASA during synergistic treatment indeed affected some key endogenous biomarkers and metabolic pathways, which could not happen when DHI or low-dose ASA was used alone. The quality and quantity of endogenous metabolite were both influenced by interaction between DHI and low-dose ASA. In details, the amount of flavin mononucleotide, L-2, 4-diaminobutyric acid (DABA) and 4-aminohippuric acid were significantly increased. On the contrary, the amount of 3-methyluridine, 4, 6-dihydroxyquinoline, cortolone-3-glucuronide, and serotonin were significantly decreased. Furthermore, O-phosphotyrosine, 3-methyl-2-butenal, indoxyl sulfate and dolichyl diphosphate were disappeared in urine. As to metabolic pathways, riboflavin metabolism, pentose and glucuronate interconversions, and tryptophan metabolism were all significantly influenced. The emerging alterations of biomarkers and metabolic pathways were associated with a lot of drugs and diseases based on literature researches, which might influence the co-administration of other drugs or the treatments of relevant diseases. Our paper presented some hints to uncover the mechanism of interaction between DHI and low-dose ASA, which would provide some references for application of DHI and low-dose ASA combination.

High-dose intravenous immunoglobulin therapy for rapidly progressive interstitial pneumonitis accompanied by anti-melanoma differentiation-associated gene 5 antibody-positive amyopathic dermatomyositis.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive amyopathic dermatomyositis (ADM) associated with rapidly progressive interstitial pneumonitis (RPIP) frequently has a poor prognosis and optimal treatment is not well defined. Here, we report a 62-year-old Japanese man with anti-MDA5 antibody-positive ADM associated with RPIP presented with progressive shortness of breath, Heliotrope rash, Gottron's papules, arthralgia, and fatigue but no sign of muscle weakness. Laboratory investigation revealed serum levels of the following biomarkers: ferritin, 1393 ng/mL; Krebs von der Lungen-6, 1880 U/mL; and creatine kinase, 85 U/L. Computed tomography (CT) images showed diffuse ground-glass opacity in both lung fields. Because anti-MDA5 was positive, we made a diagnosis of ADM associated with RPIP and initiated treatment. Following five courses of combination therapy with prednisolone, cyclosporine A, and intravenous cyclophosphamide (IVCY), IVCY treatment was switched to high-dose intravenous immunoglobulin therapy (IVIg) because of the reactivation of interstitial pneumonia with an increased serum ferritin level. Additional treatment with IVIg improved RPIP, with normalization of anti-ADM antibody levels. Therefore, IVIg mayt be a new candidate treatment for anti-MDA5 antibody-positive ADM associated with RPIP.

Commentary on the adding individual psychotherapy after relapse in a pharmacotherapy trial: commentary on the PREDICT study.

With few exceptions there has been a dearth of research evaluating the independent and combined effects of a promising medication and an effective behavioral intervention for alcohol problems. Few studies have incorporated both theory and empirical findings to ascertain how the combination of medication and behavioral intervention interact or work synergistically to produce better outcomes or why a particular combination of pharmacological and behavioral treatment works better than another combination or either of the interventions employed alone. The PREDICT Study is one of the few pharmacotherapy trials that has utilized a behavioral intervention to reduce/delay relapse to heavy drinking. The findings in the PREDICT Study were reviewed to gain a better understanding of how the combination of pharmacotherapy and behavioral intervention can be employed to manage the course of recovery for individuals with alcohol use disorders (AUDs). Findings in the PREDICT Study show that behavioral interventions and pharmacotherapies have complementary functions that can be utilized to address the differential needs, capabilities, and resources associated with AUDs. However, researchers were forced to rely mainly on their own clinical experiences rather than an overarching conceptual model in determining how the approach should be employed with AUD patients, thereby limiting the conclusions that could be drawn from the study findings. Different vulnerabilities underlying AUDs should be considered in determining what kinds of behavioral interventions should be paired with particular medications. At the same time, we need to have a better understanding of the clinical course of pharmacobehavioral treatment to deal with the array of problems/situations that arise over the course of combination therapy.

Failure of Repeated Treatment With Praziquantel and Arthemeter in Four Patients With Acute Schistosomiasis

Schistosomiasis is on the rise but still difficult to treat in international travelers; it should be suspected in patients returning from endemic areas. Praziquantel (PZQ) is not effective and may aggravate symptoms. More recently, combination treatment with artemisinin derivatives have shown promising results. We report four cases of acute schistosomiasis (AS) in which several courses of combined therapy had been necessary to obtain negative serology.

Efficacy of mizoribine followed by low-dose prednisone in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria

Background: Idiopathic membranous nephropathy (IMN) patients with persistent high-grade proteinuria are at the highest risk for developing end-stage renal failure. We previously reported the effects of treatment with mizoribine followed by low-dose prednisone treatment in 4 IMN patients. The purpose of the present study was to further assess the effects of this combined treatment in a larger study group. Method: Thirteen patients with IMN and nephrotic-range proteinuria received combined treatment. Mizoribine was initiated at a dose of 150 mg/day, and 2–3 months later, 20 mg/day prednisone was added to the mizoribine regimen. The dosage of prednisone and/or mizoribine was tapered according to the urinary protein-to-creatinine ratio (P/C). We evaluated patient responses for up to 12 months after the initiation of combination therapy. Results: Before treatment, patient urinary P/C ranged from 3.7 to 15.9 g/g. Although these values did not decrease during mizoribine monotherapy, all patients showed dramatic P/C decreases over the course of combination therapy. At 3, 6, and 12 months after combination therapy, 15%, 31%, and 62% of patients attained complete remission, respectively, and all patients were in partial or complete remission 6 months after combination therapy. No notable side effects were observed. Conclusion: The addition of prednisone after mizoribine monotherapy can be beneficial for all IMN patients with nephrotic-range proteinuria syndrome. The risks associated with immunotherapy can be decreased by initially prescribing mizoribine alone, which might act as a base for establishing therapy, followed by low-dose prednisone treatment.