Excellent Early Outcomes of Combined Chemotherapy with Arsenic Trioxide for Stage 4/M Neuroblastoma in Children A Multi center Nonrandomize d Controlled Trial

This nonrandomized, multi center cohort, open label clinical trial evaluated theefficacy and safety of combined chemotherapy with arsenic trioxide (ATO) in childrenwith stage 4/M neuroblastoma (NB). We enrolled patients who were newly diagnosedwith NB and assessed as stage 4/M and received either traditional chemotherapy or ATOcombined with chemotherapy according to their own wishes. Twenty two patients wereenrolled i n the trial group (ATO combined with chemotherapy) and thirteen patientswere enrolled in the control group (traditional chemotherapy). Objective response rate(ORR) at 4 weeks after completing induction chemotherapy was defined as the mainoutcome and adv erse events were monitored and graded in the meantime. Data cutoffdate was Dec. 31, 2019. Finally, we found that p patients who received ATO combined with chemotherapy had a significantly higher response rate than those who treated with traditional chemotherapy (ORR: 86.36% vs 46.16%, P=0.020). Reversible cardiotoxicity was just observed in 3 patients who treated with ATO and no other differential adverse events were observed between two groups. ATO combined with chemotherapy can significantly improve end-induction response in high-risk neuroblastoma and our novel regimen is well tolerated in pediatric patients. These results highlight the superiority of chemotherapy with arsenic trioxide, which creates new opportunity for prolonging survival. Besides, this treatment protocol furthest minimizes therapeutic costs compared with anti-GD2 therapy, MIBG and proton therapy, and can decrease the burden to families and society. However, we also need to bring into more cases to consolidate our conclusion.

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Cefazolin plus Ceftazidime versus Imipenem / Cilastatin Monotherapy for Treatment of Capd Peritonitis — a Randomized Controlled Trial

Peritoneal Dialysis International ◽

10.1177/089686080402400508 ◽

2004 ◽

Vol 24 (5) ◽

pp. 440-446 ◽

Cited By ~ 22

Author(s):

Chi-Bon Leung ◽

Cheuk-Chun Szeto ◽

Kai-Ming Chow ◽

Bonnie Ching-Ha Kwan ◽

Angela Yee-Moon Wang ◽

...

Keyword(s):

Treatment Group ◽

Response Rate ◽

Controlled Trial ◽

Group Versus ◽

Similar Efficacy ◽

Primary Response ◽

Control Group ◽

Cure Rate ◽

Open Label ◽

Complete Cure

Background Peritonitis is a serious complication of peritoneal dialysis (PD). We studied the efficacy of imipenem / cilastatin monotherapy in the treatment of PD-related peritonitis. Methods We performed an open-label, randomized control study comparing imipenem / cilastatin monotherapy (treatment group) versus cefazolin plus ceftazidime (control group) in the treatment of PD peritonitis. The result was further compared to a historic group treated with cefazolin plus netilmycin. Outcome measures were primary response rate at day 10 and complete cure rate. Results We enrolled 51 patients in the treatment group, 51 in the control group, and identified 96 in the historic group. The primary response rate to the assigned antibiotics was 49.0%, 51.0%, and 49.0% for the treatment, control, and historic groups, respectively ( p = 0.97). The primary response rate allowing for change in antibiotic was 82.4%, 90.2%, and 82.3%, respectively, for the three groups ( p = 0.41). The complete cure rate was 72.5%, 80.4%, and 82.3%, respectively ( p = 0.60). Tenckhoff catheter removal was needed in 6 cases in the treatment group, 6 cases in the control group, and 13 cases in the historic group ( p = 0.90). Conclusions We concluded that monotherapy of imipenem / cilastatin has similar efficacy compared to the two standard regimens of cefazolin plus ceftazidime or netilmycin in the treatment of PD peritonitis.

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Investigating the Impact of Cognitive Training for Individuals With Bothersome Tinnitus: A Randomized Controlled Trial

Otolaryngology ◽

10.1177/0194599821994742 ◽

2021 ◽

pp. 019459982199474

Author(s):

Maggie Xing ◽

Dorina Kallogjeri ◽

Jay F. Piccirillo

Keyword(s):

Randomized Controlled Trial ◽

Cognitive Training ◽

Mixed Model ◽

Controlled Trial ◽

Intervention Group ◽

Control Group ◽

Functional Index ◽

Open Label ◽

Randomized Controlled ◽

The Impact

Objective To evaluate the effectiveness of cognitive training in improving tinnitus bother and to identify predictors of patient response. Study Design Prospective open-label randomized controlled trial. Setting Online. Methods Participants were adults with subjective idiopathic nonpulsatile tinnitus causing significant tinnitus-related distress. The intervention group trained by using auditory-intensive exercises for 20 minutes per day, 5 days per week, for 8 weeks. The active control group trained on the same schedule with non–auditory intensive games. Surveys were completed at baseline, 8 weeks, and 12 weeks. Results A total of 64 participants completed the study. The median age was 63 years (range, 25-69) in the intervention group and 61 years (34-68) in the control group. Mixed model analysis revealed that within-subject change in Tinnitus Functional Index in the intervention group was not different than the control group, with marginal mean differences (95% CI): 0.24 (–11.20 to 10.7) and 2.17 (–8.50 to 12.83) at 8 weeks and 2.33 (–8.6 to 13.3) and 3.36 (–7.91 to 14.6) at 12 weeks, respectively. When the 2 study groups were compared, the control group had higher Tinnitus Functional Index scores than the intervention group by 10.5 points at baseline (95% CI, –0.92 to 29.89), 8.1 at 8 weeks (95% CI, –3.27 to 19.42), and 9.4 at 12 weeks (95% CI, –2.45 to 21.34). Conclusion Auditory-intensive cognitive training was not associated with changes in self-reported tinnitus bother. Given the potential for neuroplasticity to affect tinnitus, we believe that future studies on cognitive training for tinnitus remain relevant.

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LGG-49. SAFETY AND EFFICACY OF TRAMETINIB (T) MONOTHERAPY AND DABRAFENIB + TRAMETINIB (D+T) COMBINATION THERAPY IN PEDIATRIC PATIENTS WITH BRAF V600-MUTANT LOW-GRADE GLIOMA (LGG)

Neuro-Oncology ◽

10.1093/neuonc/noaa222.427 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii375-iii375

Author(s):

Eric Bouffet ◽

James A Whitlock ◽

Christopher Moertel ◽

Birgit Geoerger ◽

Isabelle Aerts ◽

...

Keyword(s):

Combination Therapy ◽

Pediatric Patients ◽

Objective Response ◽

Safety Data ◽

Dose Finding ◽

Combination Group ◽

Clinical Activity ◽

Low Grade ◽

Open Label ◽

Independent Review

Abstract BACKGROUND Children with BRAF V600-mutant LGG have suboptimal response to standard chemotherapy. Previously, D (BRAF V600 inhibitor) monotherapy has demonstrated clinical benefit in this population. We report interim analysis results of pediatric patients with recurrent/refractory BRAF V600-mutant LGG treated with either T (MEK1/2 inhibitor) monotherapy or D+T combination therapy. METHODS This is a 4-part, open-label, multicenter, phase I/II study (NCT02124772) in pediatric patients (<18 y) with refractory/recurrent tumors. The dose-finding phase, including dose confirmation stratified by age, was followed by disease-specific cohorts at recommended dose levels. Efficacy was determined by both investigator and independent review using RANO criteria. Adverse events (AEs) were assessed per NCI-CTCAE v4.03. RESULTS Of 49 pediatric patients with BRAF V600-mutant LGG (T, n=13; D+T, n=36) enrolled, pooled efficacy data was available for both treatments while safety data was available for 30 patients (T, n=10; D+T, n=20). Most patients (n=8/10) receiving T monotherapy withdrew/discontinued the treatment in contrast to 3/20 in the D+T group. Pyrexia occurred in 50% of patients (n=5/10) in the monotherapy group and was a frequent AE in the combination group (75%; n=15/20). Objective response rate per independent review was 15% (95% CI, 2%–45%) with T monotherapy and 25% (95% CI, 12%–42%) with D+T combination therapy. Seven patients (54%) on monotherapy and 33 patients (92%) on combination therapy had stable disease or better. CONCLUSION In pediatric patients with previously treated BRAF V600-mutant LGG, T monotherapy and D+T combination therapy demonstrated clinical activity, with pyrexia being a common AE.

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Combination of umbilical cord mesenchymal stem cells and standard immunosuppressive regimen for pediatric patients with severe aplastic anemia

BMC Pediatrics ◽

10.1186/s12887-021-02562-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yang Lan ◽

Fang Liu ◽

Lixian Chang ◽

Lipeng Liu ◽

Yingchi Zhang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Aplastic Anemia ◽

Umbilical Cord ◽

Pediatric Patients ◽

Statistical Significance ◽

Severe Aplastic Anemia ◽

Control Group ◽

Open Label ◽

Cell Counts

Abstract Background Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA). Methods We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 106/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone. Results Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153). Conclusions Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).

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Effectiveness of Measures to Eradicate Staphylococcus aureus Carriage in Patients with Community-Associated Skin and Soft-Tissue Infections: A Randomized Trial

Infection Control and Hospital Epidemiology ◽

10.1086/661285 ◽

2011 ◽

Vol 32 (9) ◽

pp. 872-880 ◽

Cited By ~ 89

Author(s):

Stephanie A. Fritz ◽

Bernard C. Camins ◽

Kimberly A. Eisenstein ◽

Joseph M. Fritz ◽

Emma K. Epplin ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Soft Tissue ◽

Controlled Trial ◽

Control Group ◽

Open Label ◽

Intention To Treat ◽

Intranasal Mupirocin ◽

Mupirocin Ointment ◽

Hygiene Education ◽

To Receive

Background.Despite a paucity of evidence, decolonization measures are prescribed for outpatients with recurrent Staphylococcus aureus skin and soft-tissue infection (SSTI).Objective.Compare the effectiveness of 4 regimens for eradicating S. aureus carriage.Design.Open-label, randomized controlled trial. Colonization status and recurrent SSTI were ascertained at 1 and 4 months.Setting.Barnes-Jewish and St. Louis Children's Hospitals, St. Louis, Missouri, 2007–2009.Participants.Three hundred patients with community-onset SSTI and S. aureus colonization in the nares, axilla, or inguinal folds.Interventions.Participants were randomized to receive no therapeutic intervention (control subjects) or one of three 5-day regimens: 2% mupirocin ointment applied to the nares twice daily, intranasal mupirocin plus daily 4% chlorhexidine body washes, or intranasal mupirocin plus daily dilute bleach water baths.Results.Among 244 participants with 1-month colonization data, modified intention-to-treat analysis revealed S. aureus eradication in 38% of participants in the education only (control) group, 56% of those in the mupirocin group (P = .03 vs controls), 55% of those in the mupirocin and chlorhexidine group (P = .05), and 63% off those in the mupirocin and bleach group (P = .006). Of 229 participants with 4-month colonization data, eradication rates were 48% in the control group, 56% in the mupirocin only group (P = .40 vs controls), 54% in the mupirocin and chlorhexidine group (P = .51), and 71% in the mupirocin and bleach group (P = .02). At 1 and 4 months, recurrent SSTIs were reported by 20% and 36% of participants, respectively.Conclusions.An inexpensive regimen of dilute bleach baths, intranasal mupirocin, and hygiene education effectively eradicated S. aureus over a 4-month period. High rates of recurrent SSTI suggest that factors other than endogenous colonization are important determinants of infection.Trial Registration.ClinicalTrials.gov identifier: NCT00513799.

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Development and evaluation of an online medication safety module for medical students at a rural teaching hospital: the Winchester District Memorial Hospital

BMJ Open Quality ◽

10.1136/bmjoq-2021-001385 ◽

2021 ◽

Vol 10 (2) ◽

pp. e001385

Author(s):

Ali Elbeddini ◽

Yasamin Tayefehchamani

Keyword(s):

Online Learning ◽

Medical Students ◽

Medication Safety ◽

Controlled Trial ◽

Effective Means ◽

Intervention Group ◽

Control Group ◽

Open Label ◽

Online Module ◽

Learning Module

ObjectiveTo design, implement and assess an online learning module for third-year and fourth-year medical students addressing medication safety.DesignThis study was a prospective, parallel, open-label, randomised controlled trial with two arms: (1) a control arm in which students were given five articles to read about medication safety, and (2) an intervention arm in which students were given access to an interactive web-based learning module on medication safety. Pretesting and post-testing were done online to evaluate change in medication safety knowledge.ResultsTen students completed the study in the intervention group (online module) and six students completed the study in the control group. The increase in score obtained on the post-test, relative to the pretest, was 15.4% in the group who completed the online module and 2.0% in the control group (difference=13.4%, 95% CI 0.5% to 26.2%, p=0.04).ConclusionStudents who completed an online educational tool about medication safety demonstrated a significantly greater increase in knowledge than those who completed a few readings. Online learning modules can be a convenient and effective means of teaching safe prescribing concepts to medical trainees.

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An Open-Label, Analgesic Efficacy and Safety of Pituitary Radiosurgery for Patients With Opioid-Refractory Pain: Study Protocol for a Randomized Controlled Trial

Neurosurgery ◽

10.1093/neuros/nyx363 ◽

2017 ◽

Vol 83 (1) ◽

pp. 146-153 ◽

Cited By ~ 2

Author(s):

Pierre-Yves Borius ◽

Stéphanie Ranque Garnier ◽

Karine Baumstarck ◽

Frédéric Castinetti ◽

Anne Donnet ◽

...

Keyword(s):

Quality Of Life ◽

Pain Relief ◽

Cancer Pain ◽

Controlled Trial ◽

Analgesic Efficacy ◽

Standards Of Care ◽

Control Group ◽

Efficacy And Safety ◽

Open Label

Abstract BACKGROUND Hypophysectomy performed by craniotomy or percutaneous techniques leads to complete pain relief in more than 70% to 80% of cases for opioid refractory cancer pain. Radiosurgery could be an interesting alternative approach to reduce complications. OBJECTIVE To assess the analgesic efficacy compared with standard of care is the primary goal. The secondary objectives are to assess ophthalmic and endocrine tolerance, drug consumption, quality of life, and mechanisms of analgesic action. METHODS The trial is multicenter, randomized, prospective, and open-label with 2 parallel groups. This concerns patients in palliative care suffering from nociceptive or mixed cancer pain, refractory to standard opioid therapy. Participants will be randomly assigned to the control group receiving standards of care for pain according to recommendations, or to the experimental group receiving a pituitary GammaKnife (Elekta, Stockholm, Sweden) radiosurgery (160 Gy delivered in pituitary gland) associated with standards of care. Evaluation assessments will be taken at baseline, day0, day4, day7, day14, day28, day45, month3, and month6. EXPECTED OUTCOMES We could expect pain improvement in 70% to 90% of cases at day4. In addition we will assess the safety of pituitary radiosurgery in a vulnerable population. The secondary endpoints could show decay of opioid consumption, good patient satisfaction, and improvement of the quality of life. DISCUSSION The design of this study is potentially the most appropriate to demonstrate the efficacy and safety of radiosurgery for this new indication. New recommendations could be obtained in order to improve pain relief and quality of life.

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Effect of conversion from calcineurin inhibitors to everolimus on hepatitis C viremia in adult kidney transplant recipients

Brazilian Journal of Nephrology ◽

10.1590/2175-8239-jbn-3860 ◽

2018 ◽

Vol 40 (2) ◽

pp. 143-150 ◽

Cited By ~ 1

Author(s):

Larissa Sgaria Pacheco ◽

Valter Duro Garcia ◽

Ronivan Luis Dal Prá ◽

Bruna Doleys Cardoso ◽

Mariana Ferras Rodrigues ◽

...

Keyword(s):

Hepatitis C ◽

Controlled Trial ◽

Calcineurin Inhibitors ◽

Control Group ◽

P Value ◽

Kidney Transplant Recipients ◽

Positive Serology ◽

Open Label ◽

Adult Kidney ◽

Group 1

ABSTRACT Introduction: Currently, there is no specific immunosuppressive protocol for hepatitis C (HCV)-positive renal transplants recipients. Thus, the aim of this study was to evaluate the conversion effect to everolimus (EVR) on HCV in adult kidney recipients. Method: This is an exploratory single-center, prospective, randomized, open label controlled trial with renal allograft recipients with HCV-positive serology. Participants were randomized for conversion to EVR or maintenance of calcineurin inhibitors. Results: Thirty patients were randomized and 28 were followed-up for 12 months (conversion group, Group 1 =15 and control group, Group 2 =13). RT-PCR HCV levels reported in log values were comparable in both groups and among patients in the same group. The statistical analysis showed no interaction effect between time and group (p value G*M= 0.852), overtime intra-groups (p-value M=0.889) and between group (p-value G=0.286). Group 1 showed a higher incidence of dyslipidemia (p=0.03) and proteinuria events (p=0.01), while no difference was observed in the incidence of anemia (p=0.17), new onset of post-transplant diabetes mellitus (p=1.00) or urinary tract infection (p=0.60). The mean eGFR was similar in both groups. Conclusion: Our study did not show viral load decrease after conversion to EVR with maintenance of antiproliferative therapy.

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Impact of valganciclovir therapy on severe IRIS-Kaposi Sarcoma mortality: an open-label, parallel, randomized controlled trial.

10.1101/2021.10.24.21265453 ◽

2021 ◽

Author(s):

Patricia Volkow ◽

Leslie Chavez-Galan ◽

Lucero Ramon-Luing ◽

Judith Cruz-Velazquez ◽

Patricia Cornejo-Juarez ◽

...

Keyword(s):

Controlled Trial ◽

Kaposi Sarcoma ◽

Pulmonary Involvement ◽

Skin Lesions ◽

Attributable Mortality ◽

Control Group ◽

Open Label ◽

Parallel Group ◽

Pulmonary Lymph Node ◽

The Difference

High HHV-8 viral load (VL) in Kaposi Sarcoma (KS) has been associated with severe Immune reconstitution inflammatory syndrome (S-IRIS-KS), which can occur after initiating cART, and is linked with high mortality particularly in patients with pulmonary involvement. We investigate if valganciclovir initiated before cART decreases HHV-8 VL and assess if it reduces the incidence of S-IRIS-KS and its attributable mortality. Methods: Open-label parallel-group randomized clinical trial in AIDS cART naive patients with disseminated KS (DKS) as defined by at least two of the following: pulmonary, lymph-node or gastrointestinal involvement, lymphedema, or equal or more 30 skin lesions. In the experimental group (EG), patients were randomized to valganciclovir 900 mg BID four weeks before cART and continued until week-48; in the control group (CG), cART was initiated on week-0. Non-severe-IRIS-KS was defined as: increase in the number of lesions plus equal or more than one log10 HIV-VL decrease or equal or more than 50 cells/mm3 increase or equal or more than 2-fold rise in baseline CD4+ cells. S-IRIS-KS was defined as abrupt clinical worsening of KS lesions and/or fever after ruling out another infection following cART initiation, and at least three of the following: thrombocytopenia, anemia, hyponatremia, or hypoalbuminemia. Results: 40 patients were randomized and 37 completed the study. In the ITT analysis, the overall mortality did not differ between groups. In the per-protocol analyses, the difference showed a trend for higher S-IRIS-KS mortality in the CG 3/19 (15.7%), compared to EG 0/18 (p=0.07). The incidence of S-IRIS KS was significantly lower in the EG; two patients, one each had S-IRIS-KS episode (0.038 per 100 patient-days) compared to CG group, four patients developed 12 S-IRIS-KS episodes (0.21 per 100 patient-days); incidence rate of 0.09 (95% CI 0.02-0.5 p=0.006). Mortality in patients with pulmonary KS was significantly lower in EG, 3/4 in CG vs 0/5 in EG. S-IRIS-KS was associated with higher HHV-8-VL; IL6 and CRP; valganciclovir was protective. Of survivors at week 48, 82% achieved more than 80% remission. No difference was found between groups in the number of non-S-IRIS-KS events. Conclusions: Valganciclovir significantly reduced the episodes of S-IRIS-KS although attributable KS mortality was lower in the EG the difference was not significant (p=0.07). Mortality was significantly lower in EG patients with pulmonary KS.

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Efficacy and Safety of Lianhuaqingwen Capsules for the Prevention of Coronavirus Disease 2019: A Prospective Open-Label Controlled Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/7962630 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Xiaowei Gong ◽

Boyun Yuan ◽

Yadong Yuan ◽

Fengju Li

Keyword(s):

Nucleic Acid ◽

Treatment Group ◽

Close Contact ◽

Controlled Trial ◽

Control Group ◽

Open Label ◽

Medical Observation ◽

Observation Period ◽

Close Contacts ◽

Nucleic Acid Tests

Coronavirus disease 2019 (COVID-19) has become a global pandemic. Community and close contact exposures continue to drive the COVID-19 pandemic. There is no confirmed effective treatment for suspected cases and close contacts. Lianhuaqingwen (LH) capsules, a repurposed Chinese herbal product that is currently on the market, have proven effective for influenza and COVID-19. To determine the safety and efficacy of LH capsules for the prevention of COVID-19, we conducted a prospective open-label controlled trial of LH capsules on subjects who had close contact with people infected with COVID-19. Subjects received LH capsules (4 capsules, three times daily) or the usual medical observation for 14 days. The primary endpoint was the rate of positive nucleic acid tests of nasal and pharyngeal swabs during the quarantine medical observation period. We included 1976 patients, including 1101 in the treatment group and 875 in the control group. The rate of positive nucleic acid tests in the treatment group was significantly lower than that in the control group (0.27% vs. 1.14%, respectively; mean difference: −0.87%; 95% CI: −1.83 to −0.13; p = 0.0174 ) during the quarantine medical observation period (14 days). Among subjects with different close contact states, there was no significant difference in the rate of positive nucleic acid test results among close contacts in the treatment group and the control group (6.45% vs. 11.43%, respectively; p = 0.6762 ). Among secondary close contacts, the rate of positive nucleic acid tests in the treatment group was significantly lower than that in the control group (0.09% vs. 0.71%, respectively; p = 0.0485 ). No serious adverse events were reported. Taken together, and in light of the safety and effectiveness profiles, these results show that LH capsules can be considered to prevent the progression of COVID-19 after close contact with an infected person. This trial is registered with ChiCTR2100043012.

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