Standard Arm Research Articles

Abstract 55: Intensive Blood Pressure Treatment Remodels Brain Perivascular Spaces: A Secondary Analysis Of The SPRINT MIND Trial

Introduction: Perivascular spaces (PVS) contribute to brain waste clearance pathways, possibly via arterial pulsatility, and are implicated in neurodegenerative disease. Aging, hypertension, and small vessel disease are associated with enlarged PVS, but the effect of intensive blood pressure (BP) control on PVS structure is unknown. Methods: This is a secondary analysis of the SPRINT-MIND MRI substudy, in which participants with cardiovascular risk but without clinical stroke were randomized to intensive BP control (systolic <120) or standard control (<140) and underwent MRI brain at baseline and 4 years. An established spatial filtering algorithm was applied to T2 images to automatically segment PVS within the supratentorial white matter and basal ganglia. PVS volumes were calculated as a percentage of the tissue volume analyzed. We tested for an effect of intensive BP treatment over time on PVS volume fraction using mixed-effects linear models, including random effects for subject and site, and fixed effects for treatment, timepoint, treatment-by-time interaction, age, and sex. Results: At randomization 658 participants had useable images (mean age = 67 years, 60% female), and PVS volume fraction was associated with age (Beta=0.0043; CI:0.0012 - 0.0076; p=0.007), white matter hyperintensity volume (B=0.18; 0.13 - 0.23; p<0.0001) and brain parenchymal fraction (B=0.011; 0.004 - 0.018; p=0.003). At mean follow-up of 3.9 years, 243 in the intensive treatment arm and 199 in the standard treatment arm had evaluable pre and post scans. PVS volume fractions were similar at randomization between treatment groups (1.38% vs 1.39%) but decreased with intensive treatment to 1.35% (p=0.022) while remaining stable with standard treatment (interaction p=0.040). Discussion: Intensive BP treatment reduces the volume of perivascular spaces. These changes may reflect remodeling of waste clearance pathways and/or volume status.

P749 Crohn’s disease stricture response and resolution with adalimumab therapy demonstrated with intestinal ultrasound. The STRIDENT randomised trial

Abstract Background Transmural healing is a treatment goal in the management of Crohn’s disease, and intestinal ultrasound (IUS) is potentially a sensitive, non-invasive and reproducible means to assess the response to treatment. Methods The STRIDENT (Stricture Definition and Treatment) study was a randomised controlled trial of standard dose monotherapy adalimumab versus intensive high-dose adalimumab combined with a thiopurine. Crohn’s disease patients with symptomatic intestinal strictures were randomised 2:1 to high dose adalimumab induction (160mg weekly for 4 weeks) with 40mg fortnightly maintenance plus thiopurine, with possible dose escalation at 4 and 8 months, versus standard dose adalimumab monotherapy. The primary endpoint was clinical response, defined as a reduction in the Obstructive Symptom Score (OSS) of ≥1, at 12 months. IUS was performed at baseline, 4, 8 and 12 months. IUS endpoints included stricture resolution (normalisation of pre-stenotic dilation (<2.5cm); reduced stricture bowel wall thickness (BWT ≥25% reduction); reduced colour doppler blood flow (inflammation, Limberg score ≤1) and normalisation of BWT (≤3mm). Patients with good quality baseline IUS and IUS-visible strictures were included for analysis. Results 77 patients underwent therapy randomisation. Of 63 patients with IUS-visible strictures 43 (68%) were in the intensive arm. Primary outcome was achieved by 32 (74%) patients in the intensive and 14 (70%) in the standard arms. Stricture resolution was seen in 1/5 non-responders and 18/45 responders. Median BWT reduced from 6.4mm (IQR 5.2-7.3mm) at baseline to 4.9mm (IQR 3-6mm) at 12 months (P<0.001). Clinical responders had significant reduction in median BWT from 6.0mm (IQR 4.5-7.1) at baseline to 4.3mm (IQR 3-5.7) at 12 months (P<0.001). There was no significant reduction in BWT at 4, 8 or 12 months in non-responders (P=0.26, P=0.29, P=0.26 respectively). BWT >3mm at 12 months occurred more often in non-responders than responders (P<0.05). Stricture resolution was seen in 13/36 in the intensive arm and 6/14 standard arm (P=0.75). The intensive arm had significant reduction in median BWT from 6.6mm (IQR 5.5-7.4mm) at baseline to 5.1mm (IQR 3-6.4mm) at 12 months (P<0.001). There was no significant reduction in BWT at 4, 8 or 12 months in the standard arm (P=0.75, P=0.42, P=0.09 respectively). There was no significant difference in BWT>3mm between trial arms at 12 months (P=1). Conclusion Stricture resolution and bowel wall thickness normalisation were demonstrated on intestinal ultrasound in stricturing Crohn’s disease patients treated with adalimumab therapy. Adalimumab therapy is associated with clinical improvement, and transmural improvement and healing, in patients with Crohn’s disease strictures.

DOP85 Crohn's Disease Strictures Respond to Drug Treatment and Treat-to-Target Intense Combination Therapy is More Effective than Standard Anti-TNF Therapy. Two year results of the STRIDENT Randomised Controlled Trial.

Abstract Background The randomised STRIDENT (Stricture Definition and Treatment) trial showed that Crohn’s disease symptomatic strictures are responsive to anti-TNF therapy with most patients clinically improved after 12 months treatment with adalimumab +/- thiopurine. Treat to target intensification resulted in greater stricture morphology improvement. We present here 2 year (from study entry) follow up to assess response durability and risk of surgery. Methods Patients with symptomatic Crohn’s disease strictures and associated inflammation (elevated faecal calprotectin and CRP) were assessed with imaging (intestinal ultrasound and MRI) and ileo-colonoscopy. The Obstructive Symptom Score (OSS) was used for clinical assessment. Patients were randomised 2:1 to high dose adalimumab induction (160mg weekly for 4 weeks) followed by 40mg fortnightly plus thiopurine, with adalimumab dose increase at 4 and/or 8 months if evidence of ongoing inflammation, versus standard dose adalimumab monotherapy. The primary endpoint was improved OSS at 12 months. Patient interview was conducted at 24 months, assessing drug treatment, symptoms, need for endoscopic therapy, hospitalisation and surgery. Results In the initial 12 months study 52 patients were randomised to the intensive and 25 to the standard treatment arm. 64/77 (83%) patients recorded an outcome at 12 months (13/77 (17%) withdrawn: 8 surgery, 5 other) 74/77 (96.1%) patients were followed up at a mean of 25.3 (IQR 24.4-26.3) months. Of these, 59 (79.7%) remained on adalimumab, 10 (13.5%) had switched to another biologic and 5 (6.7%) had ceased biologic therapy. For patients who were on adalimumab at 12 months the risk of surgery by 24 months was 15%. Of patients on adalimumab 40mg fortnightly at 12 months, 12/48 (25%) had been dose escalated by 24 months. Endoscopic balloon dilatation, hospitalisation or surgery was required in 6 (8.1%), 14 (18.9%) and 13 (17.5%) respectively; rates were not different between the standard and intensive treatment groups (P = 0.982). Median time to intestinal resection was 12.2 (IQR 6.9-18.6) months. Clinical responders at 12 months, compared to non-responders, had a reduced likelihood of surgery at 24 months (9% vs 42%, P=0.003). Conclusion Clinical response to adalimumab for structuring Crohn’s disease is durable in a majority of patients, with most patients remaining on adalimumab and avoiding surgery at two years. Rates of surgery were not different between the standard and intensive therapy arms. Clinical response to adalimumab at 12 months is an important predictor of future surgical risk.

P483 Golimumab response in Ulcerative Colitis as early as week 2: What can we take from this?

Abstract Background Golimumab is a monoclonal anti-TNF drug used in the treatment of Ulcerative Colitis (UC). GOAL-ARC is a multi-centered investigator initiated randomized control trial seeking to evaluate the utility of personalized Golimumab dose adjustment in UC versus standard dosing as per summary of product characteristics (SMPC) post-induction. From early analysis data, we aimed to ascertain if Golimumab induces response at 2 weeks and if this early response impacts disease activity at 6 weeks and the need for dose escalation at this interval. Methods Patients recruited to the trial were randomized to an intervention or a standard dosing arm. Golimumab was administered at 200mg at week 0 and 100mg at week 2 with assessments at weeks 0, 2, and 6. Baseline data was obtained including patient demographics and burden of disease. Outcomes measured were clinical response (defined by a decrease in partial mayo score of 2 points or a decrease of ≥30% from baseline), change in Faecal Calprotectin (FCP) as well as improvement in Short Health Scale (SHS) score and serum golimumab levels at 6 weeks. We also looked at FCP≤250μg/g (STRIDE II – intermediate treatment target) as an outcome. Results A total of 94 patients were recruited with 90 (95.7%) patients completing 2-week follow up and 79 (84%) patients completing 6-week follow-up. The median age was 37 years (IQR 28-46), 58.5% were male, and 76.6% (n=72) had a Mayo endoscopic subscore of 2 and the median DUBLIN Score was 4 (IQR 4-6). At 2 weeks, a clinical response was observed in 68.9% of patients (n=62). There was a significantly lower median modified partial mayo score (2 vs 4, p<0.001), rectal bleeding score (0 vs 2, p<0.001), stool frequency score (1 vs 2, p<0.001) and total SHS score (21.0 vs 25.8, p<0.001) after 2 weeks of treatment. The median FCP was numerically lower (354.7μg/g vs 1111.5μ/g, p=0.207) with an overall reduction by 32.5%. Patients who achieved a clinical response at 2 weeks were noted to have a lower baseline total SHS score (23.9 vs 29.0, p=0.017). 2-week response did not correlate with 6-week outcomes. Median FCP was significantly lower at 6 weeks (254.2μg/g vs 1111.5μ/g, p=0.008) with an overall reduction by 74.0%. There was a significantly higher median Golimumab level in patients with FCP≤250μg/g at 6 weeks (5.59μg/ml vs 2.41μg/ml, p<0.001). Conclusion Golimumab shows efficacy in Ulcerative Colitis as early as 2 weeks with significant clinical response and a biochemical response. Early data suggests that response at 2 weeks, however, is not a reliable indicator of a sustained clinical response.

Different treatment strategies versus a common standard arm (CSA) in patients with newly diagnosed AML over the age of 60 years: a randomized German inter-group study

A randomized inter-group trial comparing more intensive treatment strategies to a common standard arm 3 + 7 (CSA) was conducted in patients with non-M3 AML. Untreated patients ≥ 60 years were allocated to the CSA (n = 132) or to the study group arms (n = 1154) of the AMLCG (TAD/HAM versus HAM/HAM ± G-CSF followed by TAD and maintenance) and the OSHO (intermediate-dose ara-C/mitoxantrone followed by ara-C/mitoxantrone). Median age of the 1147 eligible patients was 69 (range 60–87) years. CR/CRi status at 90 days was not significantly different between the CSA (54% (95%CI: 45–64)) and the study group arms (53% (95%CI: 47–60) and 59% (95%CI: 58–63)). The five-year event-free survival (EFS) probability (primary endpoint) was 6.2% (95%CI: 2.7–14.0) in the CSA, 7.6% (95%CI: 4.5–12.8) in study group A and 11.1% (95%CI: 9.0–13.7) in B. The 5-year OS was 17.2% (95%CI: 11.0–26.9), 17.0% (95%CI: 2.0–23.9), and 19.5% (95%CI: 16.7–22.8) in CSA, study group A and B, respectively. Neither study group differed significantly from the CSA regarding EFS, OS, or relapse-free survival. In multivariate analyses, allocation to the treatment strategy was not significantly associated with the time-to-event endpoints. The evaluation of more intensive treatment strategies did not show clinically relevant outcome differences when compared to CSA.

Electrothermal Vessel Sealing Versus Conventional Suturing in Abdominal Hysterectomy: A Randomised Trial.

The present randomised controlled trial was conducted to compare haemostatic efficiency, operative time, and overall performance of the electrothermal bipolar vessel sealing (EBVS) system with conventional suturing in abdominal hysterectomy. The trial was designed with standard parallel arms, i.e., vessel sealing and suture ligature arms. Sixty patients were block randomised into either arms with 30 patients in each. A hand-held vessel sealing instrument was used to perform a hysterectomy in the vessel sealing arm and the quality of the uterine artery seal achieved at the first attempt was graded on an ordinal scale of 1-3 to quantify haemostatic efficiency. Operative time, intra-operative blood loss, and peri-operative complications were compared between the two arms. Significantly reduced mean operative time (26.97±8.92vs 33.67±8.62 minutes; p=0.005) and intra-operative blood loss (111±53.31 mL vs 320±193.90 mL; p=0.001) was observed in the Vessel Sealing Arm compared to Suture Ligature Arm. Of total 60 uterine seals (from bilateral uterine artery transaction in 30 hysterectomies in the Vessel Sealing Arm), 83.34% were Level 1 with Complete Seal and no residual bleeding, 8.33% were Level 2 or Partial Seals with minimal bleeding, requiring the use of vessel sealers for a second time, while 8.33% had Seal Failure (Level 3) with significant bleeding requiring additional re-security of stumps with sutures. Modal pain scores on the first three postoperative days and duration of hospital staywere significantly less in the Vessel Sealer Arm, reflecting reduced postoperative morbidity. Outcomes were comparable across operators. Vessel Sealing System gives superior surgical results with lesser operative time, minimal blood loss, and reduced morbidity.

Optimizing Peer Distribution of Syphilis Self-Testing Among Men Who Have Sex with Men in China: A Multi-City Pragmatic Randomized Controlled Trial

Syphilis testing uptake is low among men who have sex with men (MSM) around the world. Syphilis self-testing (SST) may complement facility-based testing; the distribution model is yet to be explored. This study aimed to investigate the effectiveness of peer distribution of syphilis self-testing on promoting syphilis testing. We conducted a three-arm, unblinded, parallel individually randomized controlled trial among MSM in three cities in Guangdong, China. Inclusion criteria were: men who were born biologically male, aged 18 or above, have ever had sex with a man, will refer the interventions to peers, and will take the three-month follow-up survey. Enrolled indexes were randomly assigned in a 1:1:1 ratio into standard-of-care arm (SOC arm), standard SST delivery arm (S-SST arm), and a web-based referral link SST delivery arm (RL-SST arm). The primary outcome was the number of returned photograph-verified syphilis testing results per index. A total number of 300 indexes were enrolled, with 100 indexes in each arm. The number of verified syphilis tests per index conducted by alters was 0.05 in the control arm, 0.51 in the S-SST arm, and 0.31 in the RL-SST arm. The cost per alter tested was $760.60 for SOC, $83.78 for S-SST, and $93.10 for RL-SST. Minimal adverse event was reported among both indexes and alters during the study. This study showed that peer distribution of SST could improve syphilis testing uptake among MSM in China compared to facility-based testing. This approach warrants further consideration as part of expanding syphilis self-testing.

NUTMEG: A randomized phase II study of nivolumab and temozolomide versus temozolomide alone in newly diagnosed older patients with glioblastoma.

There is an immunologic rationale to evaluate immunotherapy in the older glioblastoma population, who have been underrepresented in prior trials. The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients with glioblastoma aged 65 years and older. NUTMEG was a multicenter 2:1 randomized phase II trial for patients with newly diagnosed glioblastoma aged 65 years and older. The experimental arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant nivolumab and temozolomide. The standard arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant temozolomide. The primary objective was to improve overall survival (OS) in the experimental arm. A total of 103 participants were randomized, with 69 in the experimental arm and 34 in the standard arm. The median (range) age was 73 (65-88) years. After 37 months of follow-up, the median OS was 11.6 months (95% CI, 9.7-13.4) in the experimental arm and 11.8 months (95% CI, 8.3-14.8) in the standard arm. For the experimental arm relative to the standard arm, the OS hazard ratio was 0.85 (95% CI, 0.54-1.33). In the experimental arm, there were three grade 3 immune-related adverse events which resolved, with no unexpected serious adverse events. Due to insufficient evidence of benefit with nivolumab, the decision was made not to transition to a phase III trial. No new safety signals were identified with nivolumab. This complements the existing series of immunotherapy trials. Research is needed to identify biomarkers and new strategies including combinations.

Effect of the mHealth-supported Healthy Future programme delivered by community health workers on maternal and child health in rural China: study protocol for a cluster randomised controlled trial

IntroductionMillions of young rural children in China still suffer from poor health and malnutrition, partly due to a lack of knowledge about optimal perinatal and child care among rural mothers...

PS-C19-8: A COMPARISON OF THE MEDICATION COST AND INCIDENCE RATE OF CARDIOVASCULAR EVENTS BETWEEN INTENSIVE AND STANDARD ANTIHYPERTENSIVE PHARMACOTHERAPIES IN JAPAN

Objective: Hypertension is a major health challenge, imposing an enormous economic burden as well as health burden worldwide. In Japan, the economic burden of hypertension and related diseases is estimated to be JPY1.7 trillion (USD 13 billion) per year, around 4% of total healthcare expenditures. This study aimed to compare treatment outcomes and costs between intensive and standard pharmacotherapies, focusing on the types of antihypertensive drugs and prescribing patterns. Design and method: We performed a retrospective cohort study using electronic medical record data obtained from 34 healthcare facilities in Japan. The incidence of cardiovascular events captured via claims data was set to be the outcome measure. Multivariable mixed effects Cox-proportional hazards model was applied to compare the costs and the outcomes from intensive pharmacotherapy arm (i.e., short prescribing interval/expensive drugs) and standard one (i.e., long prescribing interval/low-cost drugs). Results: During 6,013 person-years of follow-up, 74 events were observed. While age at the beginning of treatment had significant impact on the incidence of cardiovascular events [Hazard Ratio, 1.05 (95%CI 1.02 - 1.07); p < 0.001], no associations with cardiovascular events were found for mechanism of drug action (CCB) [1.37, (95%CI 0.839 - 2.24); p = 0.21] and for short prescribing interval (less than 30 days) [1.17 (95%CI 0.695 - 1.98); p = 0.55]. The mean medication costs per day per patient of CCB and ARB were JPY 28.9 and JPY 51.8, respectively. Conclusions: No significant impacts on treatment outcomes were observed for drug type and prescribing interval, although the medication costs of intensive pharmacotherapy arm were more expensive than standard arm.

Early integration of palliative care in cervical cancer: Experiences from a pilot study.

Palliative care (PC) has been classically synonymous with end-of-life care offered to patients with advanced incurable cancers with an aim to improve their quality-of-life (QoL). However, there is growing evidence to suggest that early integration of PC (EIPC) along with cancer-directed management improves patient-reported outcomes. In this study, we aim to evaluate the impact of EIPC on QoL of cervical cancer patients treated with curative intent. Patients with locally advanced cervical cancer (stage IB2 to IIIB) having eastern cooperative oncology group (ECOG) performance score 0-2 were randomized into EIPC arm and standard of care arm of concurrent chemoradiation by a computer-generated table of random numbers. QoL was assessed by functional assessment of cancer therapy - general (FACT-G) questionnaire twice in both arms. The first assessment was done prior to starting treatment and second assessment at three months after treatment completion. The mean scores on physical, mental, emotional, social, and functional well-being subscales of FACT-G scale were calculated in both arms, and Wilcoxon test was used to evaluate differences in QoL scores within and in between the arms. This trial was registered with Clinical Trials Registry of India (CTRI) vide CTRI/2017/05/008704. Fifty patients were enrolled in each arm. However, only 42 and 45 patients in EPIC and standard oncological care arm were evaluated in the final analysis. Comparing QoL scores between the two time points in each arm, the mean pre-treatment scores in EIPC arm was significantly higher than post-treatment scores in the domains of physical and emotional well-being, whereas social and functional well-being scores improved significantly after treatment as compared with that as baseline. However, when compared between two arms, the difference of mean scores pre- and post-treatment were almost similar for physical and functional well-being but statistically significant differences were found only in social and emotional well-being scales. Our study is a feasibility study done in an attempt to test the validity of EIPC in cervical cancers. The results are inspiring to conduct robust studies in the future to explore this new domain of integration of palliative services in curable cancers.

A randomised feasibility study of serial magnetic resonance imaging to reduce treatment times in Charcot neuroarthropathy in people with diabetes (CADOM)

AimThis study aims to explore the feasibility of using serial MRI without contrast in the monitoring of Charcot neuroarthropathy to reduce duration of immobilisation of the foot, in order to decide whether a large-scale trial is warranted.MethodsA multicentre, randomised, prospective, two arm, open, feasibility study (CADOM) of people with diabetes with a suspected or confirmed diagnosis of Charcot neuroarthropathy. Participants were randomised (1:1) to ‘standard care plus’, including repeated foot temperature measurements and X-rays, or the intervention arm, with additional three-monthly MRI, until remission of Charcot neuroarthropathy or a maximum 12 months (active phase). Participants were then followed-up for a further 6 months, post remission to monitor for relapse of the Charcot neuroarthropathy (follow-up phase). Feasibility outcomes were recruitment, retention, data completeness, adherence to study procedures and safety of the intervention MRI. We also collected clinical efficacy outcomes, this included time in cast/off-loading device which will be the primary outcome of a future definitive trial. Finally, we collected patient reported outcomes, and data on health and social care usage.ResultsOne-hundred and five people were assessed for eligibility at five sites. 64/105 potential participants meet the eligibility criteria to participate in the study. Forty-three participants were randomised: 20 to standard care plus and 23 to MRI intervention. The main reason for ineligibility was a previous episode of Charcot neuroarthropathy. Thirteen participants were withdrawn post-randomisation due to an alternative diagnosis being made. Of the remaining 30 participants, 19 achieved remission, 6 had not gone into remission at the end of the 12 month active phase so exited the study. Five participants were lost to follow-up. Of the MRIs that were not disrupted by COVID-19 pandemic 26/31 (84%) were completed. For the visits that were conducted face-to-face, completion rates of patient-reported outcome measures were between 71 and 100%. There were no safety incidents associated with the intervention MRI.As this was a feasibility study it was not designed to test the effectiveness of serial MRI in diagnosing remission. The time in cast/off-loading device was 235 (±108.3) days for the standard care plus arm compared to 292 (±177.4) days for the intervention arm. There was no statistical difference in the time in cast/off-loading device between the two arms of the study: Hazard Ratio (HR) 0.405 (95% CI 0.140–1.172), p = 0.096.DiscussionThe findings support a definitive randomised controlled trial to evaluate the effectiveness of MRI in diagnosing remission in Charcot neuroarthropathy. The rates of recruitment, retention, data, and MRI completeness show that a definitive study is feasible.Study registrationISRCTN, 74101606. Registered on 6 November 2017.

A phase III, multicenter, randomized controlled trial of preoperative versus postoperative stereotactic radiosurgery for patients with surgically resectable brain metastases

BackgroundPostoperative stereotactic radiosurgery (SRS) is a standard management option for patients with resected brain metastases. Preoperative SRS may have certain advantages compared to postoperative SRS, including less uncertainty in delineation of the intact tumor compared to the postoperative resection cavity, reduced rate of leptomeningeal dissemination postoperatively, and a lower risk of radiation necrosis. The recently published ASCO-SNO-ASTRO consensus statement provides no recommendation for the preferred sequencing of radiotherapy and surgery for patients receiving both treatments for their brain metastases.MethodsThis multicenter, randomized controlled trial aims to recruit 88 patients with resectable brain metastases over an estimated three-year period. Patients with ten or fewer brain metastases with at least one resectable, fulfilling inclusion criteria will be randomized to postoperative SRS (standard arm) or preoperative SRS (investigational arm) in a 1:1 ratio. Randomization will be stratified by age (< 60 versus ≥60 years), histology (melanoma/renal cell carcinoma/sarcoma versus other), and number of metastases (one versus 2–10). In the standard arm, postoperative SRS will be delivered within 3 weeks of surgery, and all unresected metastases will receive primary SRS. In the investigational arm, enrolled patients will receive SRS of all brain metastases followed by surgery of resectable metastases within one week of SRS. In either arm, single fraction or hypofractionated SRS in three or five fractions is permitted. The primary endpoint is to assess local control at 12 months in both arms. Secondary endpoints include local control at other time points, regional/distant brain recurrence rates, leptomeningeal recurrence rates, overall survival, neurocognitive outcomes, and adverse radiation events including radiation necrosis rates in both arms.DiscussionThis trial addresses the unanswered question of the optimal sequencing of surgery and SRS in the management of patients with resectable brain metastases. No randomized data comparing preoperative and postoperative SRS for patients with brain metastases has been published to date.Trial registrationClinicaltrials.gov, NCT04474925; registered on July 17, 2020. Protocol version 1.0 (January 31, 2020). Sponsor: Alberta Health Services, Edmonton, Canada (Samir Patel, MD).

A randomized, double-blinded feasibility trial of educational materials for hiccups in chemotherapy-treated patients with cancer.

Chemotherapy can cause hiccups but few randomized controlled trials have focused on hiccups. This trial examined the feasibility of such research. This single-institution, multi-site trial used phone recruitment for patients: (1) 18years or older, (2) able to speak/read English, (3) with a working e-mail address, (4) with hiccups 4weeks prior to contact, and (5) with ongoing oxaliplatin or cisplatin chemotherapy. The primary outcome was feasibility. Patients were randomly assigned to one of two sets of educational materials, each of which discussed hiccups and palliative options. The experimental materials were almost identical to the standard materials but provided updated content based on the published medical literature. At 2weeks, patients responded by phone to a 5-item verbally administered questionnaire. This trial achieved its primary endpoint of recruiting 20 eligible patients within 5months; 50 patients were recruited in 3months. Among the 40 patients who completed the follow-up questionnaire, no statistically significant differences between arms were observed in hiccup incidence since initial contact, time spent reviewing the educational materials, and the troubling nature of hiccups. Twenty-five patients tried palliative interventions (13 in the experimental arm and 12 in the standard arm), most commonly drinking water or holding one's breath. Eleven and 10 patients, respectively, described hiccup relief after such an intervention. Clinical trials for chemotherapy-induced hiccups are feasible and could address an unmet need.

Basilar artery occlusion management: An international survey of middle versus high-income countries.

Two early basilar artery occlusion (BAO) randomized controlled trials (RCTs) did not establish the superiority of endovascular thrombectomy (EVT) over medical management. Yet many providers continued to recommend EVT. The goal of the present article is to compare physicians' diagnostic and management strategies of BAO among middle-income and high-income countries (MICs and HICs, respectively). We conducted an international survey from January to March 2022 regarding management strategies in acute BAO, to examine clinical and imaging parameters influencing clinician management of patients with BAO. We compared responses between physicians from HIC and MIC. Among the 1245 respondents from 73 countries, 799 (64.2%) were from HIC, with the remaining 393 (31.6%) from MIC. Most respondents perceived that EVT was superior to medical management for acute BAO, but more so in respondents from HIC (98.0% vs. 94.2%, p < 0.01). MIC respondents were more likely to believe further RCTs were warranted (91.6% vs. 74.0%, p < 0.01) and were more likely to find it acceptable to enroll any patient who met a trial's criteria in the standard medical treatment arm (58.8% vs. 38.5%, p < 0.01). In an area where clinical equipoise was called into question despite the lack of RCT evidence, we found that respondents from MIC were more likely to express willingness to enroll patients with BAO in an RCT than their HIC counterparts.

Experience of Paediatric Acute Lymphoblastic Leukemia Service in A Newly Established Haemato-Oncology Center in Bangladesh: Opportunities and Challenges

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and its modern management is complex. We are reporting early experience of establishing a paediatric ALL service in a multidisciplinary paediatric hospital in Bangladesh.&#x0D; Methods: This is a retrospective review of children below 18 years of age with confirmed diagnosis of ALL from July 2020 to June 2021 in Dr. M R Khan Shishu Hospital and ICH, Dhaka, Bangladesh, who received treatment adapted from the standard arm of ICICLE (Indian Childhood Collaborative Leukemia Group) protocol. Data were collected which included demographic, clinical, laboratory features of all patients at the time of presentation and also morbidities and outcome during all phases of chemotherapy. Analysis was done using descriptive statistics.&#x0D; Results: Of 51 patients, 16 were newly diagnosed patients, 32 received continuation care and 3 had relapsed disease. Treatment was initiated in 12 (75%) of 16 patients with newly-diagnosed ALL. Median age was three years, 50% were girls, one had TALL and 5 (42%) had high presentation leucocyte count (³50,000/mm3). Complete cytogenetic testing was available for one patient alone, no patient had Ph+ ALL. Eleven (92%) showed good prednisolone response. All nine patients who completed the induction phase achieved morphological remission, with high minimal residual disease (³0·01%) in two (22%). At last follow-up (30-06-2021), two patients were midway through induction, two died from sepsis (one each in Induction and Consolidation, both high risk ALL) and eight (67%) are alive in remission, on treatment 2-12 months from diagnosis. Continuation care included intrathecal treatments (n=119) and vincristine-corticosteroid pulses (n=53); 94% patient remained in complete remission, while two (6%) relapsed during the course of treatment.&#x0D; Conclusion: Risk-stratified ALL treatment is feasible in a newly established resource limited setting but limited by availability of high-quality diagnostics, specifically cytogenetics. Our study revealed that, during intensive phase approximately two-third children and during maintenance phase majority of children remained in complete remission.&#x0D; DS (Child) H J 2021; 37(2): 116-122

Effectiveness of Gamification in Knee Replacement Rehabilitation: Protocol for a Randomized Controlled Trial With a Qualitative Approach.

Exergames can provide encouraging exercise options. Currently, there is limited evidence regarding home-based exergaming in the postoperative phase of total knee replacement (TKR). This study aimed to investigate the effects of a 4-month postoperative home-based exergame intervention with an 8-month follow-up on physical function and symptoms among older persons undergoing TKR compared with home exercise using a standard protocol. In addition, a concurrent embedded design of a mixed methods study was used by including a qualitative component within a quantitative study of exergame effects. This was a dual-center, nonblinded, two-arm, parallel group randomized controlled trial with an embedded qualitative approach. This study aimed to recruit 100 patients who underwent their first unilateral TKR (aged 60-75 years). Participants were randomized to the exergame or standard home exercise arms. Participants followed a custom-made exergame program independently at their homes daily for 4 months. The primary outcomes at 4 months were function and pain related to the knee using the Oxford Knee Score questionnaire and mobility using the Timed Up and Go test. Other outcomes, in addition to physical function, symptoms, and disability, were game user experience, exercise adherence, physical activity, and satisfaction with the operated knee. Assessments were performed at the preoperative baseline and at 2, 4, and 12 months postoperatively. Exergame adherence was followed from game computers and using a structured diary. Self-reported standard exercise was followed for 4 months of intervention and physical activity was followed for 12 months using a structured diary. Qualitative data on patients' perspectives on rehabilitation and exergames were collected through laddering interviews at 4 and 12 months. This study was funded in 2018. Data collection began in 2019 and was completed in January 2022. The COVID-19 pandemic caused an unavoidable situation in the study for recruitment, data collection, and statistical analysis. As of November 2020, a total of 52 participants had been enrolled in the study. Primary results are expected to be published by the end of 2022. Our study provides new knowledge on the effects of postoperative exergame intervention among older patients with TKR. In addition, this study provides a new understanding of gamified postoperative rehabilitation, home exercise adherence, physical function, and physical activity among older adults undergoing TKR. ClinicalTrials.gov NCT03717727; https://clinicaltrials.gov/ct2/show/NCT03717727. RR1-10.2196/38434.

Convalescent or standard plasma versus standard of care in the treatment of COVID-19 patients with respiratory impairment: short and long-term effects. A three-arm randomized controlled clinical trial

BackgroundThe efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies.MethodsTo determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle.Results180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57–73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61–2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63–2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively.ConclusionsNeither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure.Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020

P077Pilot study on a novel, alternative subdermal scapular insertion site for the etonogestrel contraceptive implant

<h3>Objectives</h3> To assess the pharmacokinetics and pharmacodynamics of the etonogestrel (ENG) contraceptive implant when inserted at an alternative scapular site. <h3>Methods</h3> We conducted a pilot study of healthy, reproductive-aged women who underwent subdermal insertion of an ENG implant over the inferior edge of the non-dominant scapula (scapular insertion). We measured serum ENG levels over one year at nine time points. Participants completed questionnaires on insertion site and bleeding side effects. We collected photographs and video recordings of insertion and removal techniques. <h3>Results</h3> We enrolled five participants (as prespecified): Their median age was 26.0 (range, 19.6–30.3) and their median BMI was 25.0 kg/m2 (range, 22.0–28.0). Among five scapular implant users, all serum ENG concentrations remained >90 pg/mL during the first year of use and demonstrated bioequivalence with published data for arm insertion of ENG implant at all time points. The mean serum ENG level was 511.7±168.2 pg/mL at one week and 130.3± 19.1 pg/mL at 12 months. During the first week of insertion, four of five participants noted insertion site pain with a median pain score of 2 (range, 1–3), but all noted resolution by week two. Participants reported bleeding patterns similar to standard ENG implant use. At the end of the study, all participants were satisfied with the implant and would recommend scapular insertion to a friend. <h3>Conclusions</h3> Scapular insertion of the ENG contraceptive implant has bioequivalent pharmacokinetics to arm insertion over one year of use. This novel, alternative site was well tolerated and demonstrated similar bleeding side effects to standard arm insertion.

A pragmatic randomized controlled trial of rapid on-site influenza and respiratory syncytial virus PCR testing in paediatric and adult populations

BackgroundRapid/point-of-care respiratory virus nucleic acid tests (NAT) may improve oseltamivir, antibiotic, diagnostic test, and hospital bed utilization. Previous randomized controlled trials (RCT) on this topic have not used standard procedures of an accredited healthcare and laboratory system.MethodsWe conducted a parallel RCT at two hospitals [paediatric = Alberta Children’s Hospital (ACH); primarily adult = Peter Lougheed Centre (PLC)]. Patients with a respiratory viral testing order were randomized to testing at either a central accredited laboratory (standard arm) or with a rapid polymerase chain reaction test at an on-site accredited laboratory followed by standard testing [rapid on-site test (ROST) arm] based on day of specimen receipt at the laboratory. Patients and clinicians were blinded to assignment.The primary outcome for ACH was inpatient length of stay (LOS) and for PLC was the proportion of inpatients prescribed oseltamivir.Results706 patient encounters were included at ACH; 322 assigned to ROST (181 inpatients) and 384 to the standard arm (194 inpatients). 422 patient encounters were included at PLC; 200 assigned to ROST (157 inpatients) and 222 to the standard arm (175 inpatients).The rate of oseltamivir prescription and number of doses given was reduced in PLC inpatients negative for influenza in the ROST arm compared to standard arm [mean 14.9% (95% CI 9.87–21.9) vs. 27.5% (21.0–35.2), p = 0.0135; mean 2.85 doses (SEM 2.39–3.32) vs. 4.17 doses (3.85–4.49) p = 0.022, respectively]. ROST also significantly reduced oseltamivir use at ACH, reduced chest radiographs (ACH), and laboratory test ordering (PLC), but not antibiotic prescriptions. ROST also reduced the median turnaround time by > 24 h (ACH and PLC).The LOS at ACH was not significantly different between the ROST and standard arms [median 4.05 days (SEM 1.79–18.2) vs 4.89 days (2.07–22.9), p = 0.062, respectively].No adverse events were reported.ConclusionsIn a RCT representing implementation of ROST in an accredited laboratory system, we found that a ROST improved oseltamivir utilization and is the first RCT to show reduced ancillary testing in both paediatric and adult populations. A larger study is required to assess reduction in paediatric LOS as ACH was underpowered. These findings help justify the implementation of rapid on-site respiratory virus testing for inpatients.Trial registration ISRCTN, number 10110119, Retrospectively Registered, 01/12/2021.