Safety Of Combination Therapy Research Articles

Efficacy and Safety of Combination Therapy with Tolvaptan and Furosemide in Children with Nephrotic Syndrome and Refractory Edema: A Prospective Interventional Study.

Severe edema in children with nephrotic syndrome is often refractory to conventional diuretics. Tolvaptan has been used satisfactorily for managing edema in patients with heart failure and cirrhosis. The safety and efficacy of combination therapy with oral tolvaptan and intravenous (IV) furosemide was assessed in patients with furosemide refractory edema. Patients, aged 5-18 y with nephrotic syndrome and severe edema, were screened for eligibility. After excluding hypovolemia, patients received IV furosemide (3-4mg/kg/d) for 48h. Those refractory to IV furosemide (weight loss < 3%) received tolvaptan (0.5-1mg/kg once daily) and IV furosemide for the next 48h. Parameters were compared between 48h of furosemide alone and combination therapy. A total of 24 patients (18 boys) with mean age of 8.0 ± 3.0 y were enrolled. Urine volume significantly increased with combination therapy as compared to furosemide therapy (mean difference: 1.2mL/kg/h; 95% CI: 0.8-1.65mL/kg/h) (p < 0.001). Compared to therapy with furosemide alone, combination therapy resulted in significant reduction in body weight from 26.9 ± 10.3kg to 24.8 ± 9.7kg (p < 0.001). Estimated glomerular filtration rate did not change (p = 0.81) but serum sodium increased from 135.7 ± 3.3mEq/L to 140.4 ± 4.8mEq/L (p < 0.001) with combination therapy; 2 patients showed asymptomatic hypernatremia. The combination of oral tolvaptan and IV furosemide is effective in augmenting diuresis and reducing weight in patients with furosemide refractory edema but requires monitoring of electrolytes and volume status.

Study Protocol for a Trial: A Single-Arm, Open-Labeled Study Evaluating Transcatheter Arterial Embolization Plus Everolimus Combination Therapy for Patients With Liver Metastasis of Gastroenteropancreatic Neuroendocrine Tumors.

The number of patients with non-functional neuroendocrine tumors (NETs) has increased recently, and the rate of liver metastasis of NETs is about 20% in patients at the first diagnosis. Transcatheter arterial embolization (TAE) and everolimus are therapies with reported efficacy, but few reports have described their combined treatment. We therefore aim to evaluate the efficacy and safety of combination therapy with everolimus and TAE in patients with liver metastasis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in a prospective study. We design a single-arm, open-label, prospective study to evaluate the efficacy and safety of combination therapy with everolimus and TAE in patients with liver metastases of GEP-NETs. The study started in June 2021 at Okayama University Hospital and is expected to enroll 18 patients over a 2-year period. This study is a prospective study investigating a new treatment method for a rare disease called GEP-NETs. We may obtain useful information that contributes to the treatment guidelines in this study. However, NET is a rare disease, and although the number of cases is statistically established, it may not be possible to accurately assess causality.TRIAL REGISTRATION NUMBER: jRCT1061210015.

Immunomodulatory Effect of Traditional Chinese Medicine Combined with Systemic Therapy on Patients with Liver Cancer: A Systemic Review and Network Meta-analysis.

Objective: As immune combination therapy in the treatment of liver cancer made significant achievements, and the modulating effect of traditional Chinese medicine (TCM) on immunity gradually appeared. The main purpose of this study was to study the effect of different TCM combined with systemic therapy (ST) on immune regulation in patients with liver cancer, as well as the efficacy and safety of combined therapy, and to find the best combined application scheme by ranking.Methods: Nine electronic databases were searched from January 1, 2010, to November 12, 2021, to search for RCTs of TCM combined ST in the field of liver cancer for literature screening, quality evaluation and data extraction. STATA 15.0 and RevMan 5.3 software were used to conduct network meta-analysis to analyze and explore the significance of TCM combined ST in immune regulation, efficacy and safety in clinical application. The probability value of the surface under the cumulative ranking curve was used to rank the processing studied.Results: A total of 25 studies involving 2,152 participants were included in the network meta-analysis, including six traditional Chinese medicine injections and seven proprietary Chinese medicines. The results showed that Dahuang Zhechong Wan and Kangai injection combined with ST were the best choices for immune regulation. Moreover, the Huaier granule was the best choice to reduce vascular endothelial growth factors.Conclusion: For patients with liver cancer, TCM combined with ST was better than that of ST alone and can significantly improve the immune function of patients as well as the efficacy and safety of treatment. However, given the limited sample size and methodological quality of the trials that we included in our study, more centralized and randomized controlled trials with a large sample size are required to verify our findings.

The role of denosumab in the complex treatment of giant cell tumor of the spine: reducing of local recurrence rate, surgery time and blood loss

Objective. To assess the effect of the combined treatment method including preoperative denosumab therapy on the results of treatment of patients with giant cell tumors of the spine.Material and Methods. A single-center retrospective-prospective study of a series of clinical cases included 15 patients with giant cell tumors of vertebrae. The average follow-up period was 56 months. A total of 11 patients received denosumab therapy according to the following scheme: 120 mg subcutaneously on the 1st, 8th, 15th and 28th days of the first month and then once every 28 days. Surgical options included marginal resection, segmental resection, or en-bloc resection with or without spinal reconstruction/stabilization. In the case of locally advanced and inoperable disease, long-term therapy with denosumab was carried out until the disease progressed or serious adverse events appeared.Results. Thoracic vertebrae were involved in 7 (46.6 %) of 15 cases, lumbar in 4 (26.7 %) and cervical in 4 (26.7 %). Local recurrence rate after surgery alone was 40 % (2/5), average time to recurrence onset was 4.5 months. No relapses were observed after combined treatment performed in four patients. Disease progression during long-term denosumab therapy for inoperable disease recurrence was not recorded (0/7). The average number of denosumab injections before surgery and during long-term therapy was 15 and 24 injections, respectively. Denosumab therapy allows reducing the duration of surgery and the volume of blood loss.Conclusion. Combined therapy of giant cell vertebral tumor allows to reduce the risk of recurrence of the disease, as well as to reduce surgery duration and blood loss. Long-term continuous therapy for inoperable cases allows achieving long-term stabilization of the effect. Due to the rarity of giant cell tumors of the spine, a further prospective recruitment of patients is required to study the efficacy and safety of combined therapies.

The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

Combination of different first-line treatments for erectile dysfunction (ED) has emerged as a promising therapeutic approach. To conduct the first double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of combination therapy with low-intensity shockwave therapy (LiST) and tadalafil vs LiST and placebo in patients with mild or mild-to-moderate vasculogenic ED. Fifty sexually active patients fulfilling the eligibility criteria were randomly assigned to 6 sessions of LiST twice weekly for 3 weeks and tadalafil (n = 25) or placebo (n = 25) once daily for 4 weeks. Patients were evaluated at 1, 3, and 6 months after completion of the treatment protocol. The primary outcome was the mean change from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) domain between the 2 groups at 3 months after treatment. Erectile function was also assessed at 1 and 6 months. The number of patients attaining a minimal clinically important difference (MCID) in the IIEF-EF, as well as the safety of combination therapy were evaluated. Adjusting for the baseline values, IIEF-EF improved by 0.8 points more (95% confidence interval [CI] = -0.2 to 1.9, P = .12) at 1 month, 1 point more (95% CI = 0.1-1.9, P = .02) at 3 months and 1.7 points more (95% CI = 0.8-2.7, P < .001) at 6 months in patients treated with combination therapy compared to monotherapy. The number of patients attaining a MCID in the IIEF-EF between the 2 groups improved significantly only at the 3-month evaluation. No adverse events were reported during the whole study period. Combination of LiST twice weekly for 3 weeks and tadalafil 5 mg once daily for 4 weeks may further ameliorate mild or mild-to-moderate vasculogenic ED compared to LiST monotherapy. We conducted the first randomized trial exploring the role of LiST and tadalafil in the management of ED. Conversely, our study lacks external validity due to its single-center design. The addition of daily low-dose tadalafil during application of LiST may further improve erectile function compared to application of LiST as a standalone treatment in patients with mild or mild-to-moderate vasculogenic ED. Still, further high-quality studies are warranted to corroborate our findings.

Efficacy and safety of anal encirclement combining the Leeds-Keio artificial ligament with injection sclerotherapy using aluminum potassium sulfate and tannic acid in the management of rectal prolapse: a single-center observational study.

Perineal procedures are an important surgical option for frail and high-risk patients with rectal prolapse. This study aimed to evaluate the efficacy and safety of combined therapy using injection sclerotherapy, with aluminum potassium sulfate and tannic acid (ALTA), and the Thiersch procedure, using the Leeds-Keio ligament (ALTA-Thiersch). This study included 106 consecutive patients (mean age, 81.2 years) who underwent ALTA-Thiersch for rectal prolapse. The procedure was performed under caudal epidural anesthesia. ALTA was injected into the submucosa from the tip of the prolapsed rectum down to the dentate line, circumferentially, at 20 to 40 locations. The ligament tape was placed outside the external sphincter muscle and at an approximate depth of 2 cm into the middle anal canal. Of 106 patients, rectal prolapse was cured shortly after surgery in 105 patients. An additional tape was inserted in 1 patient who had persistent prolapse. Postoperative complications were observed in 27 patients (25.5%). Fecal impaction occurred in 12 patients; however, since it was temporary, no tape removal was required. Of the 12 cases in which the tape was infected or exposed, 11 required tape removal. There were 18 cases of recurrence at a mean follow-up of 22.1 months. Cumulative recurrence rates at 3 and 5 years were 21.3% and 38.6%, respectively. ALTA-Thiersch is a simple and safe procedure for rectal prolapse, having reasonable outcomes. The use of the Leeds-Keio ligament for anal encircling can help compensate for the disadvantages of the Thiersch operation.

Efficacy and safety of combination therapy with pramipexole and levodopa vs levodopa monotherapy in patients with Parkinson disease: A systematic review and meta-analysis.

Background:Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined effects of 2 drugs for PD patients are not completely understood.The aim of this research was to evaluate the clinical efficacy and safety of P plus L (P+L) combination therapy in the treatment of PD compared to that of L monotherapy, in order to confer a reference for clinical practice.Methods:Randomized controlled trials (RCTs) of P+L for PD published up to April, 2020 were retrieved. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale (UPDRS) scores, Hamilton depression rating scale score or adverse events.Results:Twenty-four RCTs with 2171 participants were included. Clinical efficacy of P+L combination therapy was significantly better than L monotherapy (9 trials; OR 4.29, 95% CI 2.78 to 6.64, P < .00001). Compared with L monotherapy, the pooled effects of P+L combination therapy on UPDRS score were (22 trials; SMD −1.31, 95% CI −1.57 to −1.04, P < .00001) for motor UPDRS score, (16 trials; SMD −1.26, 95% CI −1.49 to −1.03, P < .00001) for activities of daily living UPDRS score, (12 trials; SMD −1.02, 95% CI −1.27 to −0.77, P < .00001) for mental UPDRS score, (10 trials; SMD −1.54, 95% CI −1.93 to −1.15, P < .00001) for complication UPDRS score. The Hamilton depression rating scale score showed significant decrease in the P+L combination therapy compared to L monotherapy (12 trials; SMD −1.56, 95% CI −1.90 to −1.22, P < .00001). In contrast to L monotherapy, P+L combination therapy reduced the number of any adverse events obviously in PD patients (16 trials; OR 0.36, 95% CI 0.27 to 0.50, P < .00001).Conclusions:P+L combination therapy is superior to L monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+L combination therapy is better than that of L monotherapy. Further well-designed, multicenter RCTs needed to identify these findings.

P16‐96: Efficacy and safety of combination therapy of antifibrotic agents in patients with idiopathic pulmonary fibrosis

P16‐96: Efficacy and safety of combination therapy of antifibrotic agents in patients with idiopathic pulmonary fibrosis

Dipeptidyl peptidase-4 inhibitor and insulin combination treatment in type 2 diabetes and chronic kidney disease: A meta-analysis.

ABSTRACTAims/IntroductionThe union of dipeptidyl peptidase‐4 inhibitors and insulin in patients with type 2 diabetes and chronic kidney disease provides satisfactory glucose management without increasing adverse events (AEs). This research appraised the therapeutic effect and safety of combination therapy in patients with type 2 diabetes and chronic kidney disease.Materials and MethodsWe carried out a meta‐analysis of randomized controlled trials to analyze AEs, hypoglycemia, serious AEs, severe hypoglycemia, estimated glomerular filtration rate, fasting plasma glucose, glycated hemoglobin, insulin dose, low‐density lipoprotein cholesterol, uric acid and weight between combination treatment groups and control groups by searching the Cochrane Library, Excerpta Medica Database (Embase), PubMed and Web of Science databanks until October 2020.ResultsFive studies (6 trials, 1,278 participants) met the inclusion criteria. The evidence quality ranged from moderate to high. Glycated hemoglobin (standardized mean difference −0.29, 95% confidence interval −0.44 to −0.14) and insulin dose (standardized mean difference −0.16, 95% confidence interval −0.29 to −0.02) were obviously smaller in the combination cure patients than in the control patients. Compared with the control groups, combination treatment did not increase AEs, hypoglycemia, serious AEs or severe hypoglycemia.ConclusionsThis study showed the effectiveness and safety of dipeptidyl peptidase‐4 inhibitors bonded with insulin in patients with type 2 diabetes and chronic kidney disease, but the protective actions of this cure on kidney and cardiovascular outcomes, as well as the functions of other dipeptidyl peptidase‐4 inhibitors, need to be affirmed by more good‐quality randomized controlled trials.

Adjunctive therapy for acute musculoskeletal pain

Acute musculoskeletal pain (MSP) is one of the leading complaints at patients' admission. Acute MSP is usually localized in the lower back, neck, shoulder girdles, and shins. With an increase in the number of obese and hypodynamic people, the prevalence of MSP increases, especially lower back pain. Treatment of acute MSP in the back consists of informing the patient about a favorable prognosis of the disease, recommendations to maintain daily activity, primary and additional pharmacotherapy. Primary or main pharmacotherapy of acute MSP in the back includes non-steroidal anti-inflammatory drugs (NSAIDs). Adjunctive therapy is usually used in combination with NSAIDs and is aimed to increase the effectiveness of treatment and reduce the duration of NSAIDs use. As an additional therapy, muscle relaxants or B vitamins can be prescribed. The efficacy and safety of combination therapy of NSAIDs and high-dose complexes of B vitamins have been demonstrated in clinical trials involving patients with acute back pain.

Optimal timing of combining sorafenib with trans-arterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis

BackgroundThe combination therapy of trans-arterial chemoembolization (TACE) and sorafenib were proved to be one of the effective methods for intermediate and advanced hepatocellular carcinoma (HCC). Although it has been confirmed that the combination therapy can prolong survival for advanced HCC effectively, the therapeutic efficacy and safety are still controversial and the clinical value has not been determined. This meta-analysis aims to evaluate the efficacy and safety of combination therapy and discuss the optimal timing of combination for better clinical benefits. Data sourcesPubMed, EMBASE, the Cochrane Library, MEDLINE, and Web of Science were systematically reviewed to search for relevant studies published before May 15, 2021. Studies comparing the efficacy and safety of TACE + sorafenib with TACE + placebo / alone were adopted. Two reviewers independently extracted study outcomes. The data were analyzed through fixed/random-effect meta-analysis models with Review Manager (Version 5. 3) software. Results7 randomized controlled trials (RCTs) were included with 1464 patients with unresectable HCC (734 in TACE + sorafenib group and 730 in TACE + placebo or alone group). Meta-analysis showed that objective response rate (ORR) and disease control rate (DCR) were slightly improved in TACE + sorafenib group (ORR: risk ratio = 1.24; 95% confidence interval: 1.08–1.42; P = 0.002; DCR: risk ratio = 1.09; 95% confidence interval: 1.01–1.18; P = 0.02). The combination therapy obviously improved time to progression (TTP) (hazard ratio: 0.73; 95% confidence interval: 0.55–0.96; P = 0.03) and progression-free survival (PFS) (hazard ratio 0.62; 95% confidence interval: 0.52–0.73, P < 0.00001) but not overall survival (OS) (hazard ratio: 0.93; 95% confidence interval: 0.59–1.46; P = 0.75) or time to untreatable progression (TTUP) (hazard ratio: 0.76; 95% confidence interval: 0.31–1.89; P = 0.56). In addition, the incidence of adverse reactions (AEs) in combination group were higher than TACE + placebo / alone group. Furthermore, the subgroup analysis showed that the heterogeneity of TTP was notably decreased (pre-TACE: P = 0.12, I2 = 48%; post-TACE: P = 0.58, I2 = 0%), and the hazard ratio was 0.59 (95% confidence interval: 0.51–0.68; P < 0.00001) in pre-TACE subgroup which indicated that combination before TACE significantly prolonged TTP but not in combination after TACE (hazard ratio: 0.88; 95% confidence interval: 0.62–1.24; P = 0.46). In term of AEs, sensitivity analysis indicated that the risk ratio for hand-foot skin reaction, diarrhea, rash/desquamation, and hypertension was 7.41, 2.58, 2.14, 1.55 in pre-TACE subgroup respectively and was 11.34, 3.26, 3.61, 4.11 in post-TACE subgroup respectively (All P < 0.05). ConclusionThe combination of TACE and sorafenib significantly can improve TTP and PFS, and reduce the level of risk of adverse reactions of unresectable HCC, especially in the combination before TACE.

Safety of combination therapy in Staphylococcus aureus bacteraemia

Safety of combination therapy in Staphylococcus aureus bacteraemia

1238P AUTOMAN: A phase Ib/IIa study of osimertinib combined with anlotinib in EGFRm, treatment-naive advanced NSCLC patients

Osimertinib has been demonstrated superior PFS and OS compared to 1st-generation EGFR-TKIs. There is little information on efficacy and safety of combined therapy with Anlotinib which is an oral multiple-target TKI (inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret) in advanced EGFRm NSCLC patients.

Camrelizumab plus apatinib combined with TACE and cryoablation in the first-line treatment of advanced hepatocellular carcinoma.

TPS4160 Background: Hepatocellular carcinoma (HCC) is a common cancer in the world, a leading cause of cancer-related death, and especially in China. Most of the HCC patients are diagnosed at an advanced stage and require a multidisciplinary approach. The IMbrave 50 trial has reported the successful efficacy of atezolizumab and bevacizumab combination therapy in advanced hepatocellular carcinoma, which indicate the potential efficacy of combination of immunotherapy and antiangiogenesis therapy in HCC patients. In some studies, the combinatorial approaches with immunotherapy and liver directed therapies such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation are explored. Most combined interventional therapies reveal their enormous advantages as compared with any single therapeutic regimen alone, which may result from the immunologic enhancement effect of the multimodel therapy. In this study, we evaluated the efficacy and safety of combined therapy with camrelizumab plus apatinib mesylate and TACE plus cryoablation in patients with advanced HCC. Methods: This study was an open-label, single-arm, single centre, phase 2 trial in patients who were diagnosed with advanced HCC. Patients who meet the following criterias will be enrolled: (1) 18 - 75 years old; (2) Child-Pugh classification A or B(≤7);(3) Barcelona Clinic Liver Cancer stage B or C, or China liver cancer staging (CNLC) stage IIb̃IIIa; (4) Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0–1; (5) no history of previous systematic treatment; (6) expected life expectancy of more than 12 weeks; (7) adequate organs function. The key exclusion criteria were history of active autoimmune disease, or concurrent medical use of immunosuppressive medications or immunosuppressive doses of systemic corticosteroids. Eligible patients received camrelizumab 200 mg intravenously every 2 weeks and apatinib 250 mg orally once per day continuously in a treatment cycle of 4 weeks, treatment continued until 1 year or development of unacceptable toxicity or progression of disease. TACE was administrated at the first treatment cycles on day 1or 2, the chemotherapy regimens included 100-150mg oxaliplatin, 750-1000mg fluorouracil, or 30-50 mg lobaplatin, raltitrexed 2-4mg, and epirubicin 40-80 mg. Two or three weeks after the TACE, percutaneous cryoablation was performed under CT guidance. TACE and cryoablation was given as combination therapy and the periods were assessed by the investigator. The primary endpoint is objective response rate (complete or partial response according to mRECIST) and Progression-Free-Survival (Time ranges from random to the first occurrence of disease progression or death from any cause). This trial is registered with Chinese Clinical Trials Registry, ChiCTR2100043044, and is ongoing. Clinical trial information: ChiCTR2100043044.

Новые подходы к комбинированной терапии ирритативных симптомов нижних мочевыводящих путей пациентов с доброкачественной гиперплазией предстательной железы

Introduction Daytime and nighttime urinary frequency is a common complaint in patients with benign prostatic hyperplasia (BPH). The most common reason for seeking elective surgery is an ineffective treatment with alpha-blockers. The aim of the study was to evaluate the efficacy and safety of combination therapy with tamsulosin 0.4 mg and mirabegron 50 mg in patients with BPH and predominant irritative symptoms. Materials and methods from January 2018 to December 2019 in the outpatient department of the city clinical hospital named after D.D. Pletnev, a total of 64 patients with BPH with complains of frequent nighttime and daytime frequency and a desire to undergo surgery were followed. The patients underwent a comprehensive clinical and laboratory examination, according to which 10 patients had indications for surgery, and they were excluded from the study. In 6 patients, the prevalence of nocturnal over daytime diuresis was revealed and they were also excluded. Combination therapy with tamsulosin 0.4 mg and mirabegron 50 mg a day was prescribed to 48 patients. The average duration of therapy was 15.4 +/- 3.1 months. Patients underwent a follow-up examination to evaluate the efficiency and safety after 3, 6 and 12 months of therapy. Adverse events, possibly treatment-related, were recorded. Results there was an additional decrease in irritative complaints according to the I-PSS, namely 2 points after 3 months and 4 points after 6 and 12 months. In addition, a decrease in the number of nocturnal urinations by one, a decrease in daytime urination by one after 3 months and by two after 6 and 12 months, as well as an increase in the average voided volume from 150 +/- 33 to 240 +/- 40 ml after 12 months of therapy was seen. The change in other parameters was not significant. Two patients stopped taking the drug due to non-medical reasons. In other 2 patients, the development of sinus tachycardia and a transient increase in blood pressure were noted, which did not require discontinuation of the drug. Conclusions Combination therapy with tamsulosin 0.4 mg and mirabegron 50 mg reduces the frequency of daytime and night urination with the maximum effect after 6-12 months, improves the quality of life and has a good safety profile.

Combination Drug Therapy in COVID-19: Are We Using Sound Science in the Management of These Patients?

Background: Multiple case reports have shown promising results with remdesivir, tocilizumab and convalescent plasma. We evaluated the efficacy and safety of combination therapy with remdesivir, tocilizumab, steroids, antibiotics and convalescent plasma in COVID-19 patients. Objectives: To assess whether a multi-pronged approach to tackling SARS-CoV-2 had an impact on our primary end goal of decreasing the need for mechanical ventilation and identify some of the complexities involved with combination treatment regimens. Methods: In this retrospective, single center study, six confirmed SARS-CoV-2 patients with similar demographics and comorbidities treated with a combination of remdesivir, tocilizumab, antibiotics, steroids and convalescent plasma were followed. Results: At the time of initiation of treatment, all six patients were requiring at least 3 liters of supplemental oxygenation via nasal cannula. All patients received remdesivir for 5 - 10 days, tocilizumab for a total of 4 doses each across 2 days, methylprednisone and antibiotics. Commonly used antibiotics were cefepime, azithromycin, ceftriaxone and piperacillin/tazobactam. Convalescent plasma was given to three out of the six patients. Despite combination therapy with remdesivir, tocilizumab, steroids, antibiotics and convalescent plasma, four out of the six patients (66.67%) deteriorated and required invasive mechanical ventilation. Conclusions: There are currently no set treatment guidelines for COVID 19. Most institutions appear to be utilizing some form of combination therapy against COVID-19. In this study, invasive mechanical ventilation was avoided in only two of six patients despite robust use of combination therapy in all patients. Our study suggests that multiple medications may not be the answer. Instead, a clearer understanding of the pathophysiology along with timing at which medications are introduced might play a more important role. We propose judicious use of combination therapy in a methodical and sequential use in patients requiring three or more liters of supplemental oxygen. Use of any of these medications, either by itself or in combination, after mechanical ventilation has minimal if any benefits and should be used as a last resort. Currently, a few clinical trials in the recruiting stage are underway that look at various combination therapies that could provide a more comprehensive understanding regarding the efficacy of combination therapy against SARS-CoV-2.

Safety of concomitant therapy with radium-223 and abiraterone or enzalutamide in a real-world population.

Real-world utilization and outcomes of combination therapy for men with metastatic castrate-resistant prostate cancer (mCRPC) are largely unknown. We evaluated the overall survival (OS) and skeletal-related events (SREs) among men who received radium-223 with or without concomitant abiraterone or enzalutamide in the Veterans Affairs (VA) Health System. We reviewed charts of all mCRPC patients who received radium-223 in the VA from January 2013 to September 2017. We used Cox models to test the association between concomitant therapy versus radium-223 alone on OS and SRE. Sensitivity analyses were performed for concomitant use of denosumab/bisphosphonates. Three hundred and eighteen patients treated with radium-223 were identified; 116/318 (37%) received concomitant abiraterone/enzalutamide. Two hundred and seventy-seven (87%) patients died during follow-up. Patients who received concomitant therapy were younger at radium-223 initiation (median age 68 vs. 70, p = .027) and had a longer follow-up (median 29.5 vs. 17.9 months, p = .030). There was no OS benefit for those on concomitant therapy (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.67-1.12, p = .28). There was a trend for an increased SRE risk for patients on concomitant therapy (HR: 1.87, 95% CI: 0.96-3.61, p = .066), but this was not significant. When analyses were limited to men using bone heath agents, similar results were seen for OS (HR: 0.86, 95% CI 0.64-1.15, p = .30) and SRE (HR: 2.36, 95% CI: 0.94-5.94, p = .068). Despite the common use of concomitant therapy in this real-world study, there was no difference in OS among mCRPC patients. A nonsignificant increased SRE risk was observed. Further work needs to evaluate the optimal sequence, timing, and safety of combination therapies.

Efficacy and safety of combination therapy with sodium-glucose cotransporter 2 inhibitors and renin-angiotensin system blockers in patients with type 2 diabetes: a systematic review and meta-analysis.

This study was designed to evaluate the efficiency and safety of combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors and renin-angiotensin system blockers such as angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) in patients with type 2 diabetes mellitus (T2DM). We searched the PubMed, Embase, Web of Science and Cochrane Library databases from their inception to May 2020. Two authors independently performed study selection, risk-of-bias assessment and data extraction. The quality and risk of bias were assessed by the Cochrane Risk of Bias Tool. Statistical heterogeneity was determined by the I2 statistics. Seven studies including 1757 patients were analysed. Compared with ACEI/ARB alone, combination therapy with SGLT2 inhibitors and ACEIs/ARBs produced a reduction in systolic blood pressure (SBP) [weighted mean difference (WMD) -3.84 mmHg], diastolic blood pressure (DBP; WMD -1.06 mmHg), 24 h ambulatory SBP (WMD -4.59 mmHg), 24-h ambulatory DBP (WMD -2.08 mmHg), urine albumin:creatinine ratio (WMD -29.70%), evaluated glomerular filtration rate (WMD -3.46 mL/min/1.73 m2), haemoglobin A1c [standardized mean difference (SMD) -0.48], fasting plasma glucose (SMD -0.28), uric acid (SMD -0.35) and body weight (SMD -0.29). The risk of hypoglycaemia with combination therapy was higher than in the control group (risk ratio 1.37). As for the risks of total adverse events, genital infection and urinary tract infection, no significant difference was revealed. Compared with ACEI/ARB alone, the combination therapy with SGLT2 inhibitors and ACEIs/ARBs in T2DM was effective and well-tolerated and could achieve additional effects including better control of blood pressure, improvement of renal outcomes, alleviation of long-term renal function and a decrease in blood glucose and body weight. The combination therapy showed an increased risk of hypoglycaemia.

Эффективность комбинированной терапии больных эрозивной гастроэзофагеальной рефлюксной болезнью

Aim: to evaluate the efficacy and safety of combined therapy with a proton pump inhibitor (PPI) and an esophagoprotector to relieve the symptoms of reflux esophagitis, improve the life quality of patients and achieve faster and complete disease remission. Patients and Methods: a randomized study included 60 patients, including 33 men (mean age 40.96±13.44 years) and 27 women (mean age 48.29±12.69 years) with a duration of gastroesophageal reflux disease (GERD) of 21.85±15.48 months and C/D stage of reflux esophagitis. Depending on the prescribed treatment, the patients were divided into 2 groups of 30 subjects. Patients of the main group received complex therapy: PPI pantoprazole 40 mg once per day and esophagoprotector based on hyaluronic acid, chondroitin sulfate and poloxamer 407. In the comparison group, only pantoprazole was prescribed at the same dosage. The duration of the treatment course in both groups was 4 weeks. Before and after treatment, the presence and severity of complaints were assessed on the Likert scale, life quality according to the SF-36 questionnaire and endoscopic examination data. Results: after the end of the therapy course, a statistically significant decrease in the severity of epigastric burning, regurgitation, substernal pain, gaseous eructation, odynophagia and dysphagia was found both in the main group (in all cases p&lt;0.05, Wilcoxon Matched Pairs Test) and the comparison group (in all cases p&lt;0,05, Wilcoxon Matched Pairs Test). The use of combination therapy made it possible to achieve a more significant improvement in the life quality of patients in all indicators versus PPI monotherapy. In addition, 3 (10%) patients of the main group achieved endoscopic remission, while there were no such patients in the comparison group. The use of esophagoprotector in addition to PPI made it possible to reach the primary and secondary endpoints significantly more commonly versus during monotherapy. Conclusion: the obtained data indicate the high efficiency and safety of PPI therapy in combination with esophagoprotector for relieving the disease symptoms and improving the life quality of patients, faster and complete remission of reflux esophagitis by additional restoration of the esophageal mucosa resistance. Esophagoprotector as a component of complex therapy together with PPI allows achieving clinical and endoscopic disease remission in patients with erosive esophagitis in shorter terms. KEYWORDS: gastroesophageal reflux disease, esophageal mucosa resistance, esophagoprotection, proton pump inhibitor, quality of life. FOR CITATION: Matoshina I.V., Livzan M.A., Fedorin M.M., Lapteva I.V. Efficacy of combined therapy in patients with erosive gastroesophageal reflux disease. Russian Medical Inquiry. 2021;5(6):366–372 (in Russ.). DOI: 10.32364/2587-6821-2021-5-6-366-372.

Open randomized controlled trial of efficacy and safety of combination therapy for post-radiation lesions of the vaginal epithelium

Open randomized controlled trial of efficacy and safety of combination therapy for post-radiation lesions of the vaginal epithelium