ResearchPad - clinical-trial https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Clinical Trial Highlights – GLP-1 agonists]]> https://www.researchpad.co/article/elastic_article_10110 <![CDATA[Facilitators and barriers for performing comprehensive medication reviews and follow-up by multiprofessional teams in older hospitalised patients]]> https://www.researchpad.co/article/elastic_article_9951 There is a lack of knowledge about factors that influence the performance of comprehensive medication reviews (CMRs) by multiprofessional teams in hospital practice. This study aimed to explore the facilitators and barriers for performing CMRs and post-discharge follow-up in older hospitalised patients from the healthcare professional perspective.MethodsPhysicians and ward-based pharmacists were recruited from an ongoing trial at four hospitals in Sweden. Semi-structured interviews were conducted with 16 physicians and 7 pharmacists. Interview topics were working processes, resources, competences, medication-related problems, intervention effects and collaboration. The interviews were audio-recorded, transcribed verbatim and thematically analysed using the Consolidated Framework for Implementation Research (CFIR). Identified subthemes were categorised as facilitators or barriers and grouped into overarching main themes.ResultsIn total, 21 facilitators and 25 barriers were identified across all CFIR domains and grouped in 6 main themes: (a) CMRs and follow-up are needed, but not in all patients; (b) there is a general belief in positive effects; (c) lack of resources is an issue, although the performance of CMRs may save time; (d) pharmacists’ knowledge and skills are valuable, but they need more clinical competence; (e) compatibility with hospital practice is challenging, and roles and responsibilities are unclear and (f) personal contact at the ward is essential for physician-pharmacist collaboration.ConclusionMultiple facilitators and barriers for performing CMRs and post-discharge follow-up in older hospitalised patients exist. These factors should be addressed in future initiatives with similar interventions by multiprofessional teams to ensure successful implementation and performance in hospital practice.Electronic supplementary materialThe online version of this article (10.1007/s00228-020-02846-8) contains supplementary material, which is available to authorized users. ]]> <![CDATA[Phase II Study of Hypofractionated Proton Beam Therapy for Hepatocellular Carcinoma]]> https://www.researchpad.co/article/elastic_article_7495 Background: Proton beam has an excellent depth dose distribution due to its unique physical properties, and thus proton beam therapy (PBT) has been tried and showed promising outcomes in hepatocellular carcinoma (HCC). The purpose of this phase II study is to evaluate the efficacy of hypofractionated PBT in HCC.

Methods: The eligibility criteria for this study were as follows: patients with HCC lesion(s) who were failed after, were difficult to treat with, or refused to other local treatments; tumor size and number of ≤7 and ≤2 cm, respectively, and HCC lesion(s) of ≥2 cm from gastrointestinal organs; Child–Pugh score of ≤7; Eastern Cooperative Oncology Group performance status ≤1; and age ≥18 years. The prescribed dose of PBT was 70 Gy equivalent in 10 fractions. The primary endpoint was 3-year local progression-free survival (LPFS) rate.

Results: Forty-five patients were prospectively enrolled, and there were 35 men and 10 women with a median age of 63 years (range, 46–78 years). Thirty-seven patients had recurrent and/or residual disease, and eight patients had treatment-naive disease. All patients received the planned treatments without treatment interruption, and grade ≥3 acute toxicity did not occur. The median follow-up duration was 35.1 months (range, 11.2–56.3 months) and local progression occurred in two patients (8.7%). The 3-year rates of LPFS and overall survival (OS) were 95.2% (95% confidence interval [CI], 89.1%−100%) and 86.4% (95% CI, 72.9–99.9%), respectively.

Conclusion: Hypofractionated PBT showed promising LPFS and OS, and further studies are warranted to compare PBT with other local modalities.

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<![CDATA[Retrograde inspection <i>vs</i> standard forward view for the detection of colorectal adenomas during colonoscopy: A back-to-back randomized clinical trial]]> https://www.researchpad.co/article/Nf562d4f0-fe11-4a99-9b27-59cedefeda6c The adenoma detection rate (ADR) is inversely associated with the incidence of interval colorectal cancer and serves as a benchmark quality criterion during screening colonoscopy. However, adenoma miss rates reach up to 26% and studies have shown that a second inspection of the right colon in retroflected view (RFV) can increase ADR.AIMTo assess whether inspection of the whole colon in RFV compared to standard forward view (SFV) can increase ADR.METHODSPatients presenting for screening or surveillance colonoscopy were invited to participate in this randomized controlled trial and randomized into two arms. In RFV arm colonoscopy was initially performed with SFV, followed by a second inspection of the whole colon in RFV. In the SFV arm first withdrawal was performed with SFV, followed by a second inspection of the whole colon again with SFV. Number, size and morphology of polyps found during first and second inspection in each colonic segment were recorded and all polyps were removed and sent for histopathology in separate containers.RESULTSTwo hundred and five patients were randomly assigned to the RFV (n = 101) and SFV (n = 104) arm. In the RFV arm, both polyp detection rate (PDR) and ADR were increased under second inspection in RFV (PDR 1st SFV: 39.8%, PDR 2nd RFV: 46.6%; ADR 1st SFV: 35.2%, ADR 2nd RFV: 42%). Likewise, in the SFV arm, PDR and ADR were increased under second inspection (PDR 1st SFV: 37.5%, PDR 2nd SFV: 46.6%; ADR 1st SFV: 34.1%, ADR 2nd SFV: 44.3%) with no significant differences in ADR and PDR between the SFV and RFV arm. Mean number of adenomas per patient (APP) was increased in the RFV and SFV (APP RFV arm: 1st SFV: 1.71; 2nd RFV: 2.38; APP SFV arm: 1st SFV: 1.83, 2nd SFV:2.2). The majority of adenomas additionally found during second inspection in RFV or in SFV were located in the transverse and left-sided colon and were > 5 mm in size.CONCLUSIONSecond inspection of the whole colon leads to increased adenoma detection with no differences between SFV and RFV. Hence, increased detection is most likely a feature of the second inspection itself but not of the inspection mode. ]]> <![CDATA[Topical moistening of mastectomy wounds with diluted tranexamic acid to reduce bleeding: randomized clinical trial]]> https://www.researchpad.co/article/N0c45a190-1ecc-40c0-95c2-561fa05c6b26

Background

Topical administration of tranexamic acid (TXA) may be an alternative to intravenous administration to reduce bleeding with a lower risk of systemic adverse events. The aim of this study was to investigate whether moistening a surgical wound with TXA before closure, leaving a thin film of drug only, would reduce postoperative bleeding.

Methods

This was a two‐centre, stratified, parallel‐group, placebo‐controlled, double‐blind RCT. Patients undergoing mastectomy with or without axillary lymph node clearance were randomized 1 : 1 to moistening of wound surface before closure with either 25 mg/ml TXA or 0·9 per cent sodium chloride (placebo). The primary endpoint was postoperative bleeding as measured by drain production in the first 24 h. Secondary endpoints were early haematoma, total drain production, postoperative complications and late aspirations of seroma within 3 months.

Results

Between 1 January 2016 and 31 August 2018, 208 patients were randomized. Two patients were converted to a different surgical procedure at surgery, and four did not receive the intervention owing to technical error. Thus, 202 patients were included in the study (101 in the TXA and 101 in the placebo group). TXA reduced mean drain production at 24 h (110 versus 144 ml; mean difference 34 (95 per cent c.i. 8 to 60) ml, P = 0·011). One patient in the TXA group had early haematoma compared with seven in the placebo group (odds ratio (OR) 0·13 (95 per cent c.i. 0·02 to 1·07); P = 0·057). There was no significant difference in postoperative complications between TXA and placebo (13 versus 10; OR 1·11 (0·45 to 2·73), P = 0·824) or need for late seroma aspirations (79 versus 67 per cent; OR 1·83 (0·91 to 3·68), P = 0·089).

Conclusion

Moistening the wound with TXA 25 mg/ml before closure reduces postoperative bleeding within the first 24 h in patients undergoing mastectomy. Registration number: NCT02627560 (https://clinicaltrials.gov).

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<![CDATA[Dialkylcarbamoyl chloride‐coated versus alginate dressings after pilonidal sinus excision: a randomized clinical trial (SORKYSA study)]]> https://www.researchpad.co/article/N897cff3c-ae05-43e4-846d-7bcdd46fb6bc

Background

Disease of the pilonidal sinus is a common condition that affects mainly young adults. Options for management include excision of the sinus tracts, leaving the wound open to heal by secondary intention. The aim of this study was to compare wound healing with dialkylcarbamoyl chloride (DACC)‐coated dressings versus alginate dressings.

Methods

This multicentre trial randomized consecutive patients undergoing surgery for pilonidal disease to postoperative wound care with either DACC‐coated or alginate dressings. The primary outcome was the proportion of wounds healed after 75 days. Secondary outcomes were the local status of wounds during the healing process, the quality assessment of the dressings by the patient, and the time needed to return to usual activities.

Results

A total of 246 patients were included: 120 in the DACC‐coated group and 126 in the alginate group. In per‐protocol analysis, there were significantly more patients with completely healed wounds after 75 days in the DACC group than in the alginate group: 78 of 103 (75·7 per cent) versus 58 of 97 (60 per cent) respectively (odds ratio 2·55, 95 per cent c.i. 1·12 to 5·92; P = 0·023). During follow‐up, wounds with alginate dressings had more fibrin than those with DACC‐coated dressings, but the difference was not significant (P = 0·079). There was no difference between the two arms in patients' assessment of the dressings.

Conclusion

The number of wounds completely healed at 75 days was significantly higher for DACC‐coated compared with alginate dressings. However, the preplanned, clinically significant improvement in healing of 20 per cent was not reached. Registration number: NCT02011802 ( https://clinicaltrials.gov/).

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<![CDATA[A randomized study comparing docetaxel/cyclophosphamide (TC), 5-fluorouracil/epirubicin/cyclophosphamide (FEC) followed by TC, and TC followed by FEC for patients with hormone receptor-positive HER2-negative primary breast cancer]]> https://www.researchpad.co/article/N3a4a15fe-37c5-4d43-bbfd-90ba38b678d6

Purpose

Our primary objective was to determine the benefit/risk of anthracycline-free regimens by comparing docetaxel + cyclophosphamide (TC) alone, fluorouracil + epirubicin + cyclophosphamide (FEC) followed by TC, or TC followed by FEC as a primary treatment for patients with HR-positive, HER2-negative BC.

Methods

We randomized patients with stage I–III HR-positive HER2-negative, operable BC to receive either six cycles of TC (TC6), three cycles of FEC followed by three cycles of TC (FEC-TC), or three cycles of TC followed by three cycles of FEC (TC-FEC). The primary endpoint was the pathological response. Secondary endpoints included clinical response, type of surgical procedure, recurrence, death, and adverse events (by NCI-Common Terminology Criteria for Adverse Events v.3.0). We conducted all statistical analyses using SAS Version 9.2.

Results

We enrolled 195 patients and analyzed data from 193 as the intention-to-treat population. Pathological complete response rates were numerically higher in the TC6 group than in the other groups (p = 0.321). The breast conservation rate was significantly higher in the TC6 group (73%) than in the other groups (FEC-TC 51%, TC-FEC 45%, p = 0.007). Adverse events with grade > 3 were not common in the treatment groups (p = 0.569). The overall and distant disease-free survivals were similar among the groups with median follow-up of 5.80 years.

Conclusions

Despite similar long-term efficacy and safety profile, the higher breast conservation rate in the TC6 group suggests that preoperative chemotherapy without an anthracycline may benefit patients with HR-positive HER2-negative BC.

Electronic supplementary material

The online version of this article (10.1007/s10549-020-05590-w) contains supplementary material, which is available to authorized users.

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<![CDATA[A Multinational Cost-Consequence Analysis of a Bone Conduction Hearing Implant System—A Randomized Trial of a Conventional vs. a Less Invasive Treatment With New Abutment Technology]]> https://www.researchpad.co/article/N41728052-81a0-4b20-937a-9310a37fa3b1

Background: It is hypothesized that, for patients with hearing loss, surgically placing an implant/abutment combination whilst leaving the subcutaneous tissues intact will improve cosmetic and clinical results, increase quality of life (QoL) for the patient, and reduce medical costs. Here, incremental costs and consequences associated with soft tissue preservation surgery with a hydroxyapatite (HA)-coated abutment (test) were compared with the conventional approach, soft tissue reduction surgery with an all-titanium abutment (control).

Methods: A cost-consequence analysis was performed based on data gathered over a period of 3 years in an open randomized (1:1) controlled trial (RCT) running in four European countries (The Netherlands, Spain, France, and Sweden). Subjects with conductive or mixed hearing loss or single-sided sensorineural deafness were included.

Results: During the first year, in the Netherlands (NL), France (FR), and Spain (ES) a net cost saving was achieved in favor of the test intervention because of a lower cost associated with surgery time and adverse event treatments [NL €86 (CI −50.33; 219.20), FR €134 (CI −3.63; 261.30), ES €178 (CI 34.12; 97.48)]. In Sweden (SE), the HA-coated abutment was more expensive than the conventional abutment, which neutralized the cost savings and led to a negative cost (SE €-29 CI −160.27; 97.48) of the new treatment modality. After 3 years, the mean cost saving reduced to €17 (CI −191.80; 213.30) in the Netherlands, in Spain to €84.50 (CI −117.90; 289.50), and in France to €80 (CI −99.40; 248.50). The mean additional cost in Sweden increased to €-116 (CI −326.90; 68.10). The consequences in terms of the subjective audiological benefit and Health-related quality of life (HRQoL) were comparable between treatments. A trend was identified for favorable results in the test group for some consequences and statistical significance is achieved for the cosmetic outcome as assessed by the clinician.

Conclusions: From this multinational cost-consequence analysis it can be discerned that health care systems can achieve a cost saving during the first year that regresses after 3 years, by implementing soft tissue preservation surgery with a HA-coated abutment in comparison to the conventional treatment. The cosmetic results are better. (sponsored by Cochlear Bone Anchored Solutions AB; Clinical and health economic evaluation with a new Baha® abutment design combined with a minimally invasive surgical technique, ClinicalTrials.gov NCT01796236).

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<![CDATA[Caffeine Citrate for Apnea of Prematurity: A Prospective, Open-Label, Single-Arm Study in Chinese Neonates]]> https://www.researchpad.co/article/Na6967c59-8f7e-4be7-b9f9-cfa61b6d4cb5

Background: Caffeine citrate has been approved in China for the management of apnea of prematurity. This clinical trial was conducted as a condition of regulatory approval. The aim was to confirm the efficacy of caffeine citrate in the treatment of recurrent intermittent hypoxia and bradycardia in preterm newborns with primary apnea.

Objectives: The primary outcome was the change from baseline in the number of apnea events after loading dose administration of caffeine citrate. Secondary efficacy outcomes included the change from baseline in apnea events after 2 and 4 weeks of maintenance doses.

Methods: This was a multicenter, prospective longitudinal open-label, single-arm study. Neonates who had experienced at least four apnea events during a 24 h period received a loading dose of caffeine citrate 20 mg/kg; those who required additional maintenance doses received 5 mg/kg/day (titrated up to 10 mg/kg/day in case of insufficient response). The number of apnea events was recorded for 6–12 h prior to the loading dose (baseline), and for 12 h post-dose, following the loading dose and at Weeks 2 and 4 (during maintenance).

Results: A total of 247 neonates received the loading dose, who had a significant reduction from baseline of 3.9 events (p < 0.001) in the mean number of apnea events. The subset of neonates who required maintenance doses also had significant reductions in the number of events at all visits (p < 0.001 for all). A total of 79.4% of participants had at least one adverse event, but only one non-serious and no serious events were considered related to treatment.

Conclusions: In this large, prospective, open-label study, premature infants with a history of apnea who received caffeine citrate were significantly less likely to experience further apnea events.

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<![CDATA[Analysis of Differentially Expressed MicroRNAs and Circulating Tumor Cells as Predictive Biomarkers of Platinum Chemoresistance in Primary Ovarian Carcinomas: A Prospective Study]]> https://www.researchpad.co/article/Nb04831c8-6b0f-4b9d-8693-cba873c3cb23

Abstract

Lesson Learned.

  • Circulating tumor cells, microRNA markers, or other biomarkers merit examination as part of correlative scientific analyses in prospective clinical trials.

Background.

Platinum chemotherapy resistance occurs in approximately 25% of patients with ovarian carcinoma; however, no biomarkers of ovarian carcinoma chemoresistance have been validated. We performed a prospective trial designed to identify tumor‐based predictive biomarkers of platinum resistance.

Methods.

Tumor specimens were collected from 29 women with newly diagnosed histopathologically proven primary ovarian carcinoma. Of these, 23 women had specimens accessible for assessment and outcome data available regarding chemosensitive versus chemoresistance status via review of the medical record. Tumor slices were stained with antibodies against two microRNAs (miRNAs 29b and 199a) differentially expressed in chemoresistant ovarian cancer cell lines. Additionally, blood samples obtained at the time of diagnosis were analyzed for the presence of circulating tumor cells (CTCs).

Results.

The average age of the patients was 64 years, and 82.6% had high‐grade epithelial carcinomas. The baseline median CA‐125 was 464 (range 32–2,782). No statistically significant differences were observed in miR29b or 199a expression in platinum‐resistant/refractory versus platinum‐sensitive tumors. Furthermore, the presence of CTCs was not found to be statistically significantly predictive of eventual platinum resistance.

Conclusion.

Our analysis showed no differences in miR29b and 199a expression, and differences in baseline CTCs in women with newly diagnosed ovarian tumors were not statistically significant.

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<![CDATA[Effectiveness of a Multifaceted Educational Intervention to Enhance Therapeutic Regimen Adherence and Quality of Life Amongst Iranian Hemodialysis Patients: A Randomized Controlled Trial (MEITRA Study)]]> https://www.researchpad.co/article/Nb3a79736-0df0-4f2a-b012-9c2359a5c538

Purpose

A multimodal intervention designed and executed to improve therapeutic regimen adherence and quality of life in a sample of Iranian hemodialysis patients. Its feasibility and impact was assessed post intervention.

Patients and Methods

This randomized controlled trial (RCT) study was conducted at two hemodialysis wards of the Shahrvand hospital located in Sari, the capital city of the Mazandaran province, north of Iran. The study sample included patients with end-stage renal disease (ESRD) receiving outpatient hemodialysis treatment. Considering 10% attrition, 70 registered patients were randomly categorized into intervention and control groups. The proposed intervention included playing of relevant educational video tracks, conducting eight cognitive behavioral therapy (CBT) group sessions, and telephone-based peer support. Data were collected applying a set of questionnaires including sociodemographic, Beck Depression Inventory (BDI-SF), Multidimensional Scale of Perceived Social Support (MSPSS), Patient Satisfaction with Nursing Care Quality Questionnaire (PSNCQQ), End-Stage Renal Disease Adherence Questionnaire (ESRD-AQ) and the World Health Organization Quality of Life (WHOQOL-SF) scale. Sociodemographic and clinical data were collected at baseline in both groups and the postintervention assessment was performed in the intervention and nonintervention groups after one month and three months.

Results

A significant change in the self-reported depression symptoms (P=0.001), mean social support score (P=0.001), nursing care satisfaction score (P=0.001), quality of life score (P=0.001) and interdialytic weight gain (IDWG) (P=0.001) was observed among the participants in the intervention group compared to the baseline measures. The highest rise in the ESRD-AQ scores within the intervention group was observed after one month of intervention (mean difference=131.88) compared to the baseline values. Same pattern of statistically significant changes in mean scores of the intervention group’s attendants in all subscales of the ESRD-AQ were also ascertained.

Conclusion

This interventional study revealed that inaugurating of a feasible low-cost intervention without need to add major logistic or financial inputs into existing health-care systems, especially in resource limited contexts, is achievable. Findings of this study could provide insights into scientific basis of evidence-informed interventions applicable in the realm of health-care delivery.

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<![CDATA[Reporting quality and spin in abstracts of randomized clinical trials of periodontal therapy and cardiovascular disease outcomes]]> https://www.researchpad.co/article/N5a52c97b-59d0-4564-8bd9-d8b1530b3570

Objective

Poor reporting in randomized clinical trial (RCT) abstracts reduces quality and misinforms readers. Spin, a biased presentation of findings, could frequently mislead clinicians to accept a clinical intervention despite non-significant primary outcome. Therefore, good reporting practices and absence of spin enhances research quality. We aim to assess the reporting quality and spin in abstracts of RCTs evaluating the effect of periodontal therapy on cardiovascular (CVD) outcomes.

Methods

PubMed, Scopus, the Cochrane Central Register of Controlled Trials (CENTRAL), and 17 trial registration platforms were searched. Cohort, non-randomized, non-English studies, and pediatric studies were excluded. RCT abstracts were reviewed by 2 authors using the CONSORT for abstracts and spin checklists for data extraction. Cohen’s Kappa statistic was used to assess inter-rater agreement. Data on the selected RCT publication metrics were collected. Descriptive analysis was performed with non-parametric methods. Correlation analysis between quality, spin and bibliometric parameters was conducted.

Results

24 RCTs were selected for CONSORT analysis and 14 fulfilled the criteria for spin analysis. Several important RCT elements per CONSORT were neglected in the abstract including description of the study population (100%), explicitly stated primary outcome (87%), methods of randomization and blinding (100%), trial registration (87%). No RCT examined true outcomes (CVD events). A significant fraction of the abstracts appeared with at least one form of spin in the results and conclusions (86%) and claimed some treatment benefit in spite of non-significant primary outcome (64%). High-quality reporting had a significant positive correlation with reporting of trial registration (p = 0.04) and funding (p = 0.009). Spinning showed marginal negative correlation with reporting quality (p = 0.059).

Conclusion

Poor adherence to the CONSORT guidelines and high levels of data spin were found in abstracts of RCTs exploring the effects of periodontal therapy on CVD outcomes. Our findings indicate that journal editors and reviewers should consider strict adherence to proper reporting guidelines to improve reporting quality and reduce waste.

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<![CDATA[First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors]]> https://www.researchpad.co/article/N08b60ceb-51da-4bc0-816d-bad2eba09c2f

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (μg/μg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4–5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.

Electronic supplementary material

The online version of this article (10.1007/s00262-020-02483-1) contains supplementary material, which is available to authorized users.

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<![CDATA[Interpersonal Psychotherapy vs. Treatment as Usual for Major Depression Related to Work Stress: A Pilot Randomized Controlled Study]]> https://www.researchpad.co/article/N52daa274-1301-4884-98ad-2185300c033e

Background: Depressive disorders are among the leading causes of sick leave and long-term work incapacity in most modern countries. Work related stress is described by patients as the most common context of depression. It is vital to know what types of treatments are effective in improving work related problems and occupational health. However, there is only limited evidence on work-focused interventions.

Methods: The aim of our study was to evaluate the feasibility and generate first data on the effectiveness of Interpersonal Psychotherapy (IPT) adapted as a group program to focus on the work context (W-IPT). In total, 28 outpatients (22 women; M = 49.8 years old) with Major Depressive Disorder related to work stress were randomized to 8 weekly group sessions of W-IPT or to treatment as usual (TAU; guideline oriented treatment). Primary endpoint was the Hamilton Rating Scale for Depression (HRSD-24) score. Key secondary endpoints were, among others, Beck Depression Inventory (BDI-II), Work Ability Index (WAI), Return to Work Attitude (RTW-SE), and the Effort-Reward-Imbalance (ERI). In addition, we evaluated the participants' overall satisfaction with the W-IPT program by two items. A follow-up assessment was conducted 3 months after end of acute treatment.

Results: W-IPT was significantly more effective than TAU in reducing clinician-assessed depressive symptoms at follow-up (HRSD-24 W-IPT/TAU: M = 6.6/12.0, SE: 1.46/2.17, t(df = 1) = −2.24, p = 0.035, d = 0.79) and self-assessed depression (BDI-II W-IPT/TAU post-treatment: M = 8.8/18.8, SE: 1.69/2.70, t(df = 1) = −3.82, p = 0.001, d = 1.28; follow-up: M = 8.8/16.1, SE: 1.62/2.26, t(df = 1) = −2.62, p = 0.015, d = 0.99). Furthermore, W-IPT was superior in improving work-ability (WAI), return-to-work attitude (RTW-SE), and the effort-reward-ratio (ERI). No dropouts were observed in both groups. The vast majority (89 percent) of participants in the W-IPT condition were “very satisfied” with the program, although wishing for a greater number of sessions (75 percent).

Conclusions: A work-focused IPT program for the treatment of depression associated to work stress was feasible and highly acceptable. W-IPT turned out to be more effective than standard treatment in reducing depression and work-related problems. However, further evidence in a multicenter trial extending this pilot study is necessary.

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<![CDATA[A Pilot Randomized Control Trial With the Probiotic Strain Lactobacillus rhamnosus GG (LGG) in ADHD: Children and Adolescents Report Better Health-Related Quality of Life]]> https://www.researchpad.co/article/N2e233730-ed77-4273-80ae-fc0bcd5d2d44

Objectives: This double-blind pilot randomized placebo-controlled trial examined the possible effect of the probiotic strain Lactobacillus rhamnosus GG ATCC53103 (LGG) on symptoms of attention-deficit/hyperactivity disorder (ADHD), health-related quality of life (QoL), and serum levels of cytokines in children and adolescents with ADHD.

Methods: This trial evaluated 32 drug-naive children and adolescents aged between four and 17 years with a diagnosis of ADHD. The study subjects were randomly assigned to either the group that received LGG or the group that received the placebo. Assessments, comprising the ADHD Parent-Report Rating Scale-IV: Home Version; the Child Self-Report and Parent Proxy-Report of the Pediatric Quality of Life InventoryTM (PedsQLTM) 4.0 Generic Core Scale; the Parent Form (CBCL/6-18) and the Teacher Report Form (TRF) of the Child Behavior Checklist (CBCL) for ages 6–18 of the Achenbach System of Empirically Based Assessment (ASEBA); and the serum cytokines; were compared between the groups at the baseline and after 3 months.

Results: Thirty-five participants were randomized, with 32 completing the study (91.4% retention). There was a significant improvement in the PedsQL Child Self-Report Total Score after 3 months of treatment in the probiotic (p = 0.021, d = 0.53), whereas there was no significant improvement in the placebo group (p = 0.563, d = 0.04). The results of psychometric parameters assessed by parents and teachers were not so straightforward. There were statistically significant differences in the levels of serum cytokines between the groups after the 3-month treatment period: IL-6 in both the probiotic (p = 0.004, d = 0.73) and the placebo groups (p = 0.035, d = 0.94); IL-10 (p = 0.035, d = 0.6); IL-12 p70 (p = 0.025, d = 0.89); and TNF-α (p = 0.046, d = 0.64) in the probiotic group only.

Conclusions: Children and adolescents with ADHD who received LGG supplementation reported better health-related QoL compared to their peers who received the placebo. This suggests that LGG supplementation could be beneficial. But results with psychometric tests conducted by parents and teachers as well as differences in the levels of inflammatory cytokines were ambiguous. Based on these results, we propose some study modifications: a longer observation period (6–12 months); inclusion of more children's self-report assessments; recruitment of non-drug naive patients and the possible omission of serum cytokines measurements.

Clinical Trial Registration: Medical Ethics Committee (UKC-MB-KME-19-06/16).

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<![CDATA[Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial]]> https://www.researchpad.co/article/Nf9230188-d13e-4531-8ddb-6845b6660624

Purpose

The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2–3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS.

Methods

We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan–Meier methods and Cox proportional hazards models were used for analyses.

Results

Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45–1.49), osteoporosis HR 1.10 (95% CI 0.26–4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40–1.42), osteoporosis HR 1.86 (95% CI 0.43–8.01)]. Moreover, bisphosphonate use did not impact DRFS.

Conclusion

No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.

Electronic supplementary material

The online version of this article (10.1007/s10549-020-05567-9) contains supplementary material, which is available to authorized users.

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<![CDATA[De-escalation of axillary surgery in breast cancer patients treated in the neoadjuvant setting: a Dutch population-based study]]> https://www.researchpad.co/article/Nf77127db-c625-4c12-bedd-a8cc428d067f

Purpose

An overall trend is observed towards de-escalation of axillary surgery in patients with breast cancer. The objective of this study was to evaluate this trend in patients treated with neoadjuvant systemic therapy (NST).

Methods

Patients with cT1-4N0-3 breast cancer treated with NST (2006–2016) were selected from the Netherlands Cancer Registry. Patients were classified by clinical node status (cN) and type of axillary surgery. Uni- and multivariable logistic regression analyses were performed to determine the clinicopathological factors associated with performing ALND in cN+ patients.

Results

A total of 12,461 patients treated with NST were identified [5830 cN0 patients (46.8%), 6631 cN+ patients (53.2%)]. In cN0 patients, an overall increase in sentinel lymph node biopsy (SLNB) only (not followed by ALND) was seen from 11% in 2006 to 94% in 2016 (p < 0.001). SLNB performed post-NST increased from 33 to 62% (p < 0.001). In cN+ patients, an overall decrease in ALND was seen from 99% in 2006 to 53% in 2016 (p < 0.001). Age (OR 1.01, CI 1.00–1.02), year of diagnosis (OR 0.47, CI 0.44–0.50), HER2-positive disease (OR 0.62, CI 0.52–0.75), clinical tumor stage (T2 vs. T1 OR 1.32, CI 1.06–1.65, T3 vs. T1 OR 2.04, CI 1.58–2.63, T4 vs. T1 OR 6.37, CI 4.26–9.50), and clinical nodal stage (N3 vs. N1 OR 1.65, CI 1.28–2.12) were correlated with performing ALND in cN+ patients.

Conclusions

ALND decreased substantially over the past decade in patients treated with NST. Assessment of long-term prognosis of patients in whom ALND is omitted after NST is urgently needed.

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<![CDATA[The Effect of Peer Support on Hope Among Patients Under Hemodialysis]]> https://www.researchpad.co/article/N51a4d918-d6aa-4100-b816-64e083bf4294

Introduction

Providing social support for patients under hemodialysis treatment can reduce their psychological, social, and physical problems. The present study aimed at determining the effect of peer support on hopefulness in patients under hemodialysis.

Methods

This clinical trial with a pre/posttest design was conducted on 128 patients who had referred to the hemodialysis centers of Shiraz University of Medical Sciences in 2019. The patients were randomly divided into an intervention and a control group. The patients in the intervention group were supported by their peers for eight weeks and were provided with the usual care, but the controls were only provided with the usual care. The data were collected using Snyder Hope Scale. Then, the data were entered into the SPSS software, version 18 and were analyzed using independent t-test and paired t-test.

Results

At baseline, the participants in both groups were similar with respect to the mean scores of hope and its subscales (p>0.05). However, there was a significant difference between the two groups in terms of hope and its subscales eight weeks after the intervention (p<0.001).

Conclusion

The results confirmed the effect of peer support on increasing hope among the patients under hemodialysis. Peer support in informational, emotional, instrumental, and spiritual forms could create a positive incentive and increase hope among the patients.

Clinical Trial Number

This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT20190126042498N1).

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<![CDATA[Efficacy and safety of trelagliptin in Japanese patients with type 2 diabetes with severe renal impairment or end‐stage renal disease: Results from a randomized, phase 3 study]]> https://www.researchpad.co/article/N28786e03-2947-4543-9416-276cdfeda351

Abstract

Introduction

To investigate the efficacy and safety of trelagliptin 25 mg in patients with type 2 diabetes mellitus with severe renal impairment or end‐stage renal disease.

Materials and Methods

This multicenter, randomized, phase 3 study comprised a 12‐week double‐blind phase followed by a 40‐week open‐label phase. Patients had type 2 diabetes mellitus with severe renal impairment (creatinine clearance <30 mL/min) or end‐stage renal disease (undergoing hemodialysis), and were receiving diet and/or exercise therapy with/without one antidiabetic drug.

Results

Patients were randomized to trelagliptin (A/A, n = 55) or placebo (P/A, n = 52; double‐blind phase). Both groups received trelagliptin in the open‐label phase. The least square mean change (95% confidence interval [CI]) from baseline in hemoglobin A1c at the end of the double‐blind phase was −0.71% (95% CI −0.885, −0.542) and 0.01% (95% CI −0.170, 0.183) in the A/A and P/A groups, respectively (intergroup least square means difference −0.72%, 95% CI −0.966, −0.473; < 0.0001). Mean hemoglobin A1c decreased after trelagliptin treatment in the P/A group to similar levels observed in the A/A group and remained comparable in both groups versus baseline up to week 52. In the double‐blind phase, the incidence of treatment‐emergent adverse events (TEAEs) was 72.7% and 61.5% in the A/A and P/A group, respectively; most TEAEs were mild‐to‐moderate, except in one patient (P/A group), who experienced two severe TEAEs. The incidence of serious TEAEs was 7.3% and 3.8% in the A/A and P/A group, respectively.

Conclusions

Once‐weekly trelagliptin 25 mg was efficacious, with no major safety concerns, and represents a meaningful treatment option in this patient population.

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<![CDATA[Efficacy and safety of once‐weekly exenatide after switching from twice‐daily exenatide in patients with type 2 diabetes]]> https://www.researchpad.co/article/Naa3eb025-3be6-480b-8fd9-a5f532271294

Abstract

Aims/Introduction

To evaluate the efficacy and safety of once‐weekly (q.w.) extended‐release exenatide after switching from twice‐daily (b.i.d.) exenatide in patients with type 2 diabetes.

Materials and Methods

This was an investigator‐initiated, prospective, single‐arm, multicenter study. Individuals with type 2 diabetes who had been treated with exenatide b.i.d. for at least 3 months were enrolled and switched to exenatide q.w. for 24 weeks. The primary end‐point was change in HbA1c at week 24 to test the glucose‐lowering effect of exenatide q.w. versus exenatide b.i.d.

Results

A total of 58 Japanese individuals with type 2 diabetes completed the study. Glycated hemoglobin was reduced by 0.2% at week 24 (7.2 ± 1.2% vs 7.0 ± 1.2% [56 ± 13 vs 53 ± 13 mmol/mol], 95% confidence interval −0.4 to −0.03%, P < 0.005 for non‐inferiority, P = 0.01 for superiority). Fasting plasma glucose was reduced by 12 mg/dL at week 24 (154 ± 46 vs 142 ± 46 mg/dL, P = 0.02). β‐Cell function assessed by homeostasis model assessment of β‐cell function and C‐peptide index was significantly improved at week 24. The incidence of self‐reported hypoglycemia was reduced, and treatment satisfaction assessed by the Diabetes Treatment Satisfaction Questionnaire and Diabetes Medication Satisfaction Questionnaire was improved at week 24, with no change in body weight. There was no serious adverse event related to the study drug.

Conclusions

Switching from exenatide b.i.d. to exenatide q.w. resulted in a reduction in glycated hemoglobin, fasting plasma glucose and the incidence of hypoglycemia, and improvement in β‐cell function and treatment satisfaction in patients with type 2 diabetes. These findings will be useful for selecting optimal treatment in individuals with type 2 diabetes.

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