Standard Arm Research Articles

CKD Progression following Acute Kidney Injury: A Secondary Analysis of the STARRT-AKI Trial.

Chronic kidney disease (CKD) is a common complication after acute kidney injury (AKI). We aimed to evaluate whether RRT initiation strategy had an effect on CKD progression. Secondarily, we aimed to identify factors that influenced the development or progression of CKD following severe AKI. This secondary analysis of the STARRT-AKI trial included participants with outpatient serum creatinine values available in the year prior to hospitalization and who were alive at 90 days following randomization. Our main analysis focused on patients who had definitive assessment of kidney function at 90 days following randomization. Predictor markers included patient demographics, co-morbidities, markers of acute illness, laboratory values, receipt of renal replacement therapy (RRT), and RRT treatment strategy (accelerated versus standard). The primary outcome was CKD progression, a composite of de novo CKD, defined as new eGFR < 60 ml/min/1.73 m2 if baseline eGFR was ≥ 60 ml/min; a decline in eGFR ≥ 25% if baseline eGFR was < 60 ml/min, or RRT dependence at day 90. The association of RRT treatment strategy with CKD progression was assessed in an unadjusted mixed-effect logistic regression model. Of the 401 surviving patients with a baseline serum creatinine, 39% experienced CKD progression. RRT initiation strategy had no effect on CKD progression (accelerated arm (41%), vs. the standard arm (38%), Odds ratio 1.13, (95% confidence interval 0.75 to 1.72)). Receipt of RRT and aortic surgery were the most potent risks of CKD progression. These findings suggest that CKD progression is common after severe AKI. Risk factors for CKD progression included receipt of RRT and aortic surgery, suggested that these individuals should be prioritized for dedicated kidney follow up after hospital discharge.

Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Stage III Non-Small Cell Lung Cancer.

NRG-RTOG0617 demonstrated a detrimental effect of uniform high-dose radiation in stage III non-small cell lung cancer. NRG-RTOG1106/ECOG-ACRIN6697 (ClinicalTrials.gov identifier: NCT01507428), a randomized phase II trial, studied whether midtreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can guide individualized/adaptive dose-intensified radiotherapy (RT) to improve and predict outcomes in patients with this disease. Patients fit for concurrent chemoradiation were randomly assigned (1:2) to standard (60 Gy/30 fractions) or FDG-PET-guided adaptive treatment, stratified by substage, primary tumor size, and histology. All patients had midtreatment FDG-PET/CT; adaptive arm patients had an individualized, intensified boost RT dose to residual metabolically active areas. The primary therapeutic end point was 2-year centrally reviewed freedom from local-regional progression (FFLP), defined as no progression in or near the planning target volume and/or regional nodes. FFLP was analyzed on a modified intent-to-treat population at a one-sided Z-test significance level of 0.15. The primary imaging end point was centrally reviewed change in SUVpeak from baseline to midtreatment; its association with FFLP was assessed using the two-sided Wald test on the basis of Cox regression. Of 138 patients enrolled, 127 were eligible. Adaptive-arm patients received a mean 71 Gy in 30 fractions, with mean lung dose 17.9 Gy. There was no significant difference in centrally reviewed 2-year FFLP (59.5% and 54.6% in standard and adaptive arms; P = .66). There were no significant differences in protocol-specified grade 3 toxicities, survival, or progression-free survival (P > .4). Median SUVpeak and metabolic tumor volume (MTV) in the adaptive arm decreased 49% and 54%, from pre-RT to mid-RT PET. However, ΔSUVpeak and ΔMTV were not associated with FFLP (hazard ratios, 0.997; P = .395 and .461). Midtreatment PET-adapted RT dose escalation as given in this study was safe and feasible but did not improve efficacy outcomes.

INNV-25. POST-OPERATIVE LOW DOSE VERSUS STANDARD DOSE DEXAMETHASONE FOR MANAGEMENT OF CEREBRAL EDEMA: A RANDOMIZED, DOUBLE-BLINDED FEASIBILITY STUDY IN PATIENTS WITH PRIMARY OR METASTATIC BRAIN TUMORS UNDERGOING CRANIOTOMY FOR TUMOR RESECTION

Abstract INTRODUCTION Although dexamethasone is effective for controlling cerebral edema during the peri-operative period, its immunosuppressive properties can inhibit responses to immunotherapy. We hypothesized that patients with mild to moderate cerebral edema could be safely managed post-operatively with lower doses of dexamethasone. METHODS Eligible patients with brain tumors who had less than 10 mm of midline shift on their pre-operative brain MRIs were randomized 1:1 to the standard or low dose dexamethasone arm, each tapering double blinded through post-op day 8. The double blind was maintained using equivalent volumes for IV doses and capsules containing dexamethasone or placebo. By post-op day 9, participants received the same dose of dexamethasone and continued tapering to off by day 14. Additional doses of dexamethasone were allowed if needed, based on specified symptom criteria. Lack of feasibility was defined as a participant requiring 18 mg or more of dexamethasone in addition to the planned total dose of dexamethasone (low dose: 49 mg; standard dose: 112 mg). Brain MRIs were performed on post-operative days 1, 3, and 8 to evaluate changes in cerebral edema. Manual segmentation and computer-assisted techniques were used to quantitatively measure cerebral edema volume. RESULTS Twenty-six patients were randomized and treated within tumor type strata (primary versus metastatic), of which 25 were evaluable. None of the participants on the low dose dexamethasone arm met the criteria for lack of feasibility. The quantitative assessment of differences in cerebral edema between the arms is ongoing and will be presented. CONCLUSIONS Administration of lower doses of dexamethasone post-operatively to brain tumor patients with mild to moderate cerebral edema is feasible. Treatment with lower doses of dexamethasone post-operatively should be considered in this patient population when peri-operative administration of immunotherapy is planned.

Dynamics of peritoneal transport and cardiovascular outcomes of peritoneal dialysis treatment

BACKGROUND: Solute and water transport by peritoneal membrane has significant variation between patients; the function changes significantly over time. This affects treatment outcomes and requires individual approaches. AIM: To evaluate the influence of the baseline peritoneal transport state, its dynamics during peritoneal dialysis and the possibility of long-term outcomes modification. MATERIALS AND METHODS: The dynamics of peritoneal transport of solutes (in peritoneal equilibrium test, PET) and water (in mini-PET) was evaluated in a prospective interventional open-label study with historical control among 96 unselected consecutive patients admitted in three dialysis centers with unified program of peritoneal membrane monitoring and protection. RESULTS: Compared to the matched standard arm, the increase in peritoneal solute transport was significantly slower (by 9.5%) in the observation group. Ultrafiltration in classical PET decreased more slowly (by 28%). At baseline ultrafiltration was satisfactory (the proportion of the patients with ultrafiltration less 400 ml was 7.6%); water transport by small pores did not decrease (−1.1 ± 5.9 ml/year), and the decrease in total ultrafiltration (by 32.1 ± 8.2 ml/year) was due to a decrease in free water transport (by 29.9 ± 7.6 ml/year). Negative dynamics of free water transport was associated with total glucose load and with monthly glucose load greater than 2.68 kg/month. More than one case of peritonitis was associated with a more rapid decline in free water transport. The comorbidity increased in 34 of 96 patients, with median first/last scores of 5 (4–6) and 6 (4–7) points; (Wilcoxon Z = −5.423; p 0.001). When analyzed separately by peritoneal transport category, a significant worsening of the comorbidity index was observed only for high average and high transporters (Z = −2.754, p = 0.006 and Z = −3.357, p = 0.001, respectively). CONCLUSIONS: The interaction between peritoneal transport, primarily free water transport, and cardiovascular disease is certainly two-way: deterioration of water balance due to loss of effective ultrafiltration leads to volume overload and progression of cardiovascular disease. On the other hand, cardiovascular disease contributes to peritoneal membrane damage. The most sensitive monitoring of interventions effectiveness in membrane protection and preventing cardiovascular disease progression is the separate measuring of water transport through small pores and ultrapores, which simultaneously reveals a feature of progressive peritoneal fibrosis, a potential precursor of encapsulating peritoneal sclerosis.

Embedding a text message recall system to increase the uptake of cardiovascular screening in Australian general practice. Results of the Text to Detect randomised controlled trial

Abstract Background Australian guidelines recommend cardiovascular disease (CVD) risk screening for adults aged 45-74 years, but less than one in three have blood pressure and cholesterol recorded within their general practitioner (GP) records. Medicare subsidised ‘Heart Health Checks’ were introduced in primary care in 2019, however uptake has been suboptimal. Purpose The aims of this study were to; 1) implement a text mediated Heart Health Check recall program within general practice at scale, 2) determine whether uptake can be increased with nudge reminder text messages and 3) evaluate the impact on risk factor measurement and medication prescription. Methods Australian general practices were invited via advertisement and mailing list. Medical record software identified patients eligible for a Heart Health Check. Practices were randomised to one of three arms: 1) standard SMS: 1 SMS inviting patients to see their GP for a Heart Health Check, 2) nudge reminder: standard SMS + nudge reminder two weeks later, 3) control: no SMS. Aggregate, deidentified, practice-level data was extracted at baseline and 3-months. The primary outcome was the proportion of Heart Health Checks delivered at a practice level. Secondary outcomes included updated CVD risk factor assessment and new medication prescriptions. Analyses used ANOVA and Tukey's HSD. Results Between 2022 and 2023, 206 general practices participated, each with 560 median eligible patients (IQR:297-909). A total of 70,679 recall text messages and 34,406 nudge reminder messages were sent. Heart Health Check uptake was 11 and 16 times higher in the standard and nudge arms (respectively) compared to control (0.4 vs 4.5 vs 6.3 per 100 patients, p&amp;lt;0.001), with a 40% statistically significant increase (p=0.02) for 2 SMS vs 1 SMS. Updated cholesterol values were 31.6 and 60.2% higher in standard and nudge arms (respectively) compared to control (13.7 vs 16.8 vs 17.4 per 100 patients, p=0.02). Both active arms were statistically significantly different from control (standard p=0.047, nudge p=&amp;lt;0.001). Updated blood pressure was 23.0 and 26.8% higher in the standard and nudge arms (respectively) compared to control (13.7 vs 16.8 vs 17.4 per 100 participants), however only the nudge arm was statistically significantly different (p=0.38). New medication prescription (lipid or blood pressure-lowering) was 36.8% higher in the nudge arm compared to control (32.1 vs 43.9 patients per practice, p=0.03). Conclusions This study demonstrates the effectiveness of text mediated recall of eligible patients to increase the uptake of cardiovascular risk screening in Australian general practice. The findings will inform the implementation of new Australian guidelines and policy reform.

Influence of orthostatic blood pressure changes on the effects of intensive blood pressure control in patients with type 2 diabetes

Abstract Background Intensive blood pressure (BP) control has been proven to reduce the risks of major cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM) (1). Excessive orthostatic BP changes should be fully addressed, given its high prevalence and associations with adverse events among T2DM patients (2-5). However, the benefits of intensive BP control among T2DM patients with significant orthostatic BP changes have been equivocal. Purpose To examine whether orthostatic BP changes modify the efficacy of intensive BP control on CVD outcomes in patients with T2DM. Methods The Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) is a 2×2 factorial designed trial that aimed to evaluate the effects of intensive glycemia and BP control on major CVD events among T2DM patients (6). We enrolled participants with at least one record of orthostatic BP values for analysis. The composite CVD outcome in this study comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalized congestive heart failure. Associations between orthostatic BP changes and the composite CVD outcome and all-cause death, respectively, were presented by restricted cubic spline curves based on multivariable Cox models. We examined if the effects of intensive BP control varied across the orthostatic BP change for the composite CVD outcome and all-cause death. Results Among 4330 participants, 877 (20.3%) experienced episodes of orthostatic hypotension (OH) at baseline or during follow-up. There was no significant difference in the proportions of OH participants between the intensive and standard BP arms. U-shaped associations were observed between orthostatic systolic BP changes and the composite CVD outcome, as well as all-cause mortality (Figure 1). In the standard glycemia arm, intensive BP control was significantly associated with a lower risk of composite CVD outcome (HR 0.76, 95%CI 0.59-0.97). There was a beneficial association of intensive BP control with all-cause mortality without statistical significance (HR 0.85, 95%CI 0.56-1.30). The favorable effect of intensive BP control was not influenced by orthostatic BP changes (P for interaction 0.51 for the composite CVD outcome and 0.97 for all-cause mortality) (Figure 2). Beneficial effects of intensive BP control were not observed for participants in the intensive glycemia arm on the composite CVD outcome (HR 0.99, 95%CI 0.76-1.28) and all-cause mortality (HR 1.19, 0.79-1.80). Conclusion Orthostatic BP changes should not be a barrier to intensive BP control for T2DM patients treated with guideline-recommended standard glycemia control.

Tracking modifications to implementation strategies: a case study from SNaP - a hybrid type III randomized controlled trial to scale up integrated systems navigation and psychosocial counseling for PWID with HIV in Vietnam

IntroductionEvaluation of implementation strategies is core to implementation trials, but implementation strategies often deviate from the original plan to adjust to the real-world conditions. The optimal approach to track modifications to implementation strategies is unclear, especially in low-resource settings. Using data from an implementation trial for people who inject drugs (PWID) with HIV in Vietnam, we describe the tracking of implementation strategy modifications and present findings of this process.MethodsSNaP (Systems Navigation and Psychosocial Counseling) is a hybrid type-III effectiveness-implementation randomized controlled trial aiming to scale up the evidence-based intervention, integrated systems navigation and psychosocial counseling, for PWID with HIV in Vietnam. Forty-two HIV testing sites were randomized 1:1 to a standard or tailored arm. While the standard arm (SA) received a uniform package of strategies, implementation strategies for the tailored arm (TA) were tailored to address specific needs of each site. The central research team also met monthly with the TA to document how their tailored strategies were implemented over time. Five components were involved in the tracking process: describing the planned strategies; tracking strategy use; monitoring barriers and solutions; describing modifications; and identifying and describing any additional strategies.ResultsOur approach allowed us to closely track the modifications to implementation strategies in the tailored arms every month. TA sites originally identified 27 implementation strategies prior to implementation. During implementation, five strategies were dropped by four sites and two new strategies were added to twelve sites. Modifications of five strategies occurred at four sites to accommodate their changing needs and resources. Difficulties related to the COVID-19 pandemic, low number of participants recruited, high workload at the clinic, lack of resources for HIV testing and high staff turnover were among barriers of implementing the strategies. A few challenges to tracking modifications were noted, including the considerable amount of time and efforts needed as well as the lack of motivation from site staff to track and keep written documentations of modifications.ConclusionsWe demonstrated the feasibility of a systematic approach to tracking implementation strategies for a large-scale implementation trial in a low-resource setting. This process could be further enhanced and replicated in similar settings to balance the rigor and feasibility of implementation strategy tracking. Our findings can serve as additional guidelines for future researchers planning to report and track modifications to implementation strategies in large, complex trials.Trial registration: clinicaltrials.gov ID: NCT03952520 (first posted 2019-05-16).

Out-of-pocket costs for patients diagnosed with high-grade glioma and their carers

Abstract Background This study aimed to describe the out-of-pocket costs incurred by patients diagnosed with high-grade glioma and their carers in the standard care arm of the Care-IS trial in the six to eight months following their diagnosis. Methods Carers completed monthly cost surveys detailing the out-of-pocket costs incurred by patients and carers over a six-month period. Seventy carers reported out-of-pocket costs at baseline (within two months following patient diagnosis), and a maximum of 50% of participants reported costs in any subsequent month. Costs were adjusted to 2023 AUD and reported as medians with interquartile range. Demographic factors were assessed to determine if any were significantly associated with being in the first or fourth quartile of total out-of-pocket costs at baseline. Results Median monthly costs for patient-carer dyads were highest at baseline ($535(IQR:$170-$930)), and two months post-recruitment ($314 (IQR:$150-$772)). The largest contributors to patient-carer costs were patient health service use and patient medications. Patient and carer health service use and medication costs varied over time. The median health service use and medication out-of-pocket costs for patients and carers were mostly below $100 per month, however, there was large variance in the upper 75th percentile for these cost categories. No factors were significantly associated with higher baseline out-of-pocket costs. Conclusion A HGG diagnosis has a significant and sustained financial impact on people who are diagnosed and their carers. Patients experience significant additional costs relating to their diagnosis and travel to receive care, and their carers also continue to experience sustained costs whilst managing the additional tasks associated with informal caregiving.

Pragmatic randomised trial assessing the impact of peer comparison and therapeutic recommendations, including repetition, on antibiotic prescribing patterns of family physicians across British Columbia for uncomplicated lower urinary tract infections

ObjectiveTo evaluate the impact of a personalised audit and feedback prescribing report (AF) and brief educational summary (ES) on empiric treatment of uncomplicated lower urinary tract infections (UTIs) by family...

Prospective study on the impact of different antithrombotic therapies on subclinical leaflet thickening and its temporal dynamics in transcatheter aortic valves—The NOTION-4 trial

Transcatheter aortic valve replacement (TAVR) has become the standard-of-care treatment for a majority of patients with severe, symptomatic aortic stenosis. The post-procedural anti-thrombotic therapeutic management is still a topic of debate and could affect the incidence of HALT, a phenomenon which can be assessed by four-dimensional computed tomography (4DCT). The NOTION-4 trial is a randomized controlled trial comprising TAVR patients with no indication for oral anticoagulant (OAC) therapy, comparing lifelong single anti-platelet therapy (standard arm) versus early 3-month direct oral anticoagulant (DOAC) therapy followed by single anti-plateletet therapy (experimental arm). The incidence of HALT and clinical endpoints will be evaluated in both groups at 3 months, 1 year and 5 years after randomization. The primary endpoint is the number of patients with at least one bioprosthetic aortic valve leaflet with HALT as assessed by cardiac 4DCT imaging at 1 year. The trial is powered for superiority testing and started enrollment in 2021. In total, 324 patients will be included. The last patient is expected to be enrolled by the end of 2024 and the primary endpoint is to be presented in 2026. The NOTION-4 trial aims to study whether an early 3-month DOAC therapy after TAVR can result in a sustained lower incidence of HALT in transcatheter aortic valves. This trial holds the potential to give valuable insights into whether early OAC therapy should be integrated in future guidelines for post-TAVR anti-thrombotic therapeutic management. NOTION-4, ClinicalTrials.gov ID NCT06449469, https://clinicaltrials.gov/study/NCT06449469.

Longitudinal Health-Related Quality of Life Among Patients With High-Risk Pediatric Hodgkin Lymphoma Treated on the Children's Oncology Group AHOD 1331 Study.

PURPOSEThere have been no previous longitudinal assessments of health-related quality of life (HRQoL) during treatment for pediatric Hodgkin lymphoma (HL). The addition of brentuximab vedotin (BV) to a multidrug chemotherapy backbone demonstrated superior efficacy to standard chemotherapy for patients with pediatric high-risk HL in the AHOD 1331 trial. However, the impact on HRQoL is unknown.PATIENTS AND METHODSAfter treatment random assignment, 268 participants older than 11 years were enrolled in a prespecified, longitudinal, patient-reported outcomes substudy. HRQoL was assessed using the seven-item Child Health Ratings Inventories (CHRIs)-Global scale before treatment (T1) and at cycle 2 (T2), cycle 5 (T3), and end of treatment (T4). A clinically meaningful increase in HRQoL was considered 7 points on the CHRIs-Global. Multivariable linear regression estimated associations between demographic/clinical variables and HRQoL at T1. Linear mixed models estimated changes in HRQoL across the treatment arm.RESULTSParticipant characteristics were balanced by treatment arm. Ninety-three percent of participants completed the CHRIs at T1, 92% at T2, 89% at T3, and 77% at T4. At T1, female sex and fever (P < .05) were each associated with worse HRQoL. By T2, participants in the BV arm experienced a statistically and clinically significant improvement in HRQoL (β = 7.3 [95% CI, 3.2 to 11.4]; P ≤ .001), which was greater than the change in the standard arm (difference in change β = 5.1 [95% CI, -0.2 to 10.3]; P = .057). The standard arm did not experience a statistically or clinically significant increase in HRQoL until T4 (β = 9.3 [95% CI, 4.7 to 11.5]; P < .001).CONCLUSIONThese data demonstrate successful collection of serial HRQoL from youth with high-risk pediatric HL and improvement in HRQoL over the course of initial therapy, sooner and to a greater extent in the group receiving the novel agent BV.

Intensive FVIII replacement in hemophilia patients with hypertrophic synovium: a randomized study

BackgroundHypertrophic synovium (HS) is a marker of disease activity in persons with hemophilia (PwH). Although some recommendations suggest intensifying prophylaxis in PwH with HS, no validated schedules are available. ObjectivesWe explored the efficacy of intensive factor VIII (FVIII) replacement treatment in PwH with HS. MethodsIn a randomized, open-label study, PwH with HS were randomized to receive pharmacokinetics-driven prophylaxis targeting a FVIII trough level of 8% to 12% (intensive treatment arm [ITA]) or 3% to 5% (standard treatment arm [STA]). The primary outcome was HS reduction/resolution in the 2 treatment arms. ResultsA total of 39 PwH were randomized to ITA and 36 to STA. During the study, we found a lower annual bleeding rate and a higher rate of annual bleeding rate zero in the ITA than in the STA. HS reduction/resolution was reported in 35.9% of cases in the ITA and 8.4% in the STA. In detail, in the ITA ,10.3% achieved HS reduction and 25.6% complete HS resolution, as compared to 5.6% and 2.8% in the STA. Cox regression showed that ITA was associated with HS reduction/resolution (hazard ratio: 4.75; 95% CI: 1.36-16.57; P = .014) and HS complete resolution (hazard ratio: 10.79; 95% CI: 1.38-84.45; P = .023). The analysis of the 127 joints with HS (54 elbows, 41 knees, and 32 ankles) consistently confirmed similar results. ConclusionIn this randomized study, we found a ∼5-fold higher rate of HS reduction/resolution and a ∼10-fold higher rate of HS resolution in the ITA than in the STA.

Protocol-Stipulated Dose Modification to Manage Chemotherapy-Induced Peripheral Neuropathy in Children, Adolescents, and Young Adults With High-Risk Hodgkin Lymphoma.

Brentuximab vedotin (BV) incorporation into frontline chemotherapy regimens improved outcomes for classic Hodgkin lymphoma (cHL). The shared mechanism of action of BV and vinca alkaloids as microtubulin inhibitors increased the potential risk of chemotherapy-induced peripheral neuropathy (CIPN). Rates of CIPN and use of protocol-stipulated dose modifications of a microtubulin inhibitor were examined on the Children's Oncology Group AHOD1331 study, which compared BV, doxorubicin, vincristine (VCR), etoposide, prednisone, cyclophosphamide (BV-AVE-PC; BV arm) with bleomycin containing doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC; standard arm) in patients with high-risk cHL ages 2-21 years. AHOD1331 required clinician grading and reporting of ≥grade 2 CIPN. Protocol-stipulated dose modifications of VCR preceded modification of BV for ≥grade 2 CIPN in the BV arm, but only required modification of VCR for ≥grade 3 in the standard arm. Outcomes included CIPN rates, dose modification of microtubulin inhibitors by study arm, clinical factors associated with dose modifications, and event-free survival (EFS) by the presence of dose modification. Among the 582 patients who began protocol therapy, 112 developed ≥grade 2 CIPN. Cumulative incidence of CIPN did not differ by study arm (19.2 v 19.8%, P = .91). CIPN dose modifications occurred more frequently in the BV arm (9.5% v 2.8%, P = .001); however, most patients with CIPN on the BV arm received full-dose BV. EFS did not differ by the presence of dose modifications after accounting for study arm, age, sex, and stage, although older age was significantly associated with the risk of VCR dose modifications for CIPN. A staged dose modification plan for vinca alkaloids and BV as administered in AHOD1331 minimized the effect of incorporating a second microtubulin inhibitor on CIPN without compromising treatment efficacy in the BV arm.

Zero-Contrast Transcatheter Aortic Valve Implantation vs. Standard Practice: Periprocedural and Long-Term Clinical Outcomes.

Background: We aimed to compare the procedural efficacy and long-term clinical results of a totally contrast-free Transcatheter Aortic Valve Implantation (TAVI) procedure (i.e., contrast dye was not used for either the pre-procedural assessment or during the procedure) to those of standard practice in patients with severe renal dysfunction. Methods: All consecutive patients with a glomerular filtration rate (GFR) ≤ 35 mL/min and severe aortic stenosis who were treated with transfemoral TAVI at our Institution were included in the registry. The zero-contrast patients underwent carbon dioxide angiography and a non-contrast CT scan for assessment of vascular access suitability, and aortic annulus sizing was performed by a TEE, and the procedural guidance was fluoroscopic and echocardiographic. Procedural outcomes were evaluated, and clinical long-term follow-up was performed for all included patients. Results: A total of 44 patients (median age, 85 (IQR, 80.75-87.00)) were included in the zero-contrast group (TEE guidance and general anesthesia in 37 (84%) patients), while 63 patients were included in the standard practice arm (82 ± 78 mL of contrast dye used). Procedural success was obtained in 100% of cases. There were no differences in procedural outcomes, including final mean aortic gradients (5.5 (IQR, 5.0-10.0) mmHg in the zero-contrast group vs. 6.0 (IQR, 5.0-10.0) mmHg in the standard practice group) and rate of at least a moderate paravalvular leak (0% vs. 1.6% in the zero-contrast and standard practice groups, respectively; p = 0.31). No differences in AKI during the hospital stay were observed. Over a median follow-up of 3.3 years, there was a significantly lower rate of AKI (1.2% vs. 25.9%, p < 0.001) and rehospitalizations (1.6% vs. 35.5%, p < 0.00) in standard practice group. Conclusions: We showed for the first time the feasibility and efficacy of a totally contrast-free strategy compared to standard practice in TAVI patients with severe renal dysfunction. Besides achieving comparable procedural results, the zero-contrast strategy showed a better long-term clinical outcome in reducing hospital readmissions for kidney function deterioration.

A pilot pragmatic randomized controlled trial of a nicotine metabolite ratio-guided smoking cessation intervention in a lung health and screening program

IntroductionPatients with pulmonary nodules detected through lung cancer screening or as incidental findings are often followed in lung health and screening programs. The use of personalized pharmacotherapy for smoking cessation informed by the nicotine metabolite ratio (NMR), a measure of nicotine metabolism, has not yet been evaluated in this setting. This pilot randomized controlled trial (RCT) evaluated the feasibility of conducting a larger trial. MethodsThrough a pragmatic RCT design, participants were recruited from a Mid-Atlantic lung health and screening program. Eligible participants smoked >5 cigarettes per day and completed a blood draw to determine NMR before being randomized to standard or NMR-guided care treatment arms. Standard care participants were offered nicotine replacement therapy (NRT) or varenicline and a referral to phone-based smoking cessation counseling. NMR-guided participants received standard care except they were provided a personalized medication recommendation based on their NMR. Study outcomes included measures of feasibility, medication uptake, and treatment matching (i.e., uptake of the optimal medication). ResultsMore than 80 % of 205 screened patients were eligible. However, only 37 (22 %) of these patients enrolled in the study, with a mean age of 65 years, 43 % female, and 25 % Black. Nearly all patients who declined cited a disinterest in smoking cessation. Participants in both treatment arms had high rates of medication uptake (68 %), with NMR-guided participants showing a trend towards greater treatment matching (55 % vs. 29 %). ConclusionsThe results of this pilot study provide support for conducting a larger RCT of an NMR-guided smoking cessation intervention in a lung health and screening setting. Consideration should be given to augmenting the intervention to address barriers to study entry.

Basilar artery occlusion management: An international survey of gender influence on management.

The superiority of endovascular thrombectomy (EVT) over medical management was not established in two early basilar artery occlusion (BAO) randomized controlled trials. Despite this, many clinicians recommended EVT for acute BAO under certain circumstances. This paper aims to compare physicians' diagnostic and management strategies of BAO according to gender. From January to March 2022 an international survey was conducted regarding management strategies in acute BAO. We compared responses between clinicians by identifying gender. Questions were designed to examine clinical and imaging parameters influencing management of patients with BAO. Among the 1245 respondents from 73 countries, 311 (25.0%) identified as female. This figure was 13.6% amongst interventionists. Geographically, female respondents were lowest in Asia (14.5%) and North America (23.9%). The proportion of respondents identifying as female was consistent regardless of their years of experience. Female respondents were more likely to choose time of onset as time of first estimated stroke like symptom (48.0% vs. 38.5%, p < .01), were less likely to favor thrombectomy in the V4 segment of vertebrobasilar artery occlusions (31.5% vs. 43.3%, p < .01), and were less likely to find it acceptable to enroll all patients who met trial criteria in the standard medical treatment arm of a clinical trial (41.2% vs. 47.0%, p = .01). Male respondents were more likely to agree that thrombolysis would not alter their decision on proceeding with EVT (93.7% vs. 88.3%, p < .01). Female clinicians appear to be significantly underrepresented in stroke medicine. This is most pronounced amongst interventionists and in Asia. Although male and female opinions were closely aligned on many aspects of BAO management, differences in opinion were observed in a number of significant areas which influence decision making.

HYPCON trial: A phase II randomized study evaluating hypofractionated versus conventional adjuvant radiation therapy in head and neck malignancies.

143 Background: Hypofractionated RT has been established as standard of care at many cancer sites but there is limited data on use of hypofractionated RT for head and neck carcinomas (HNC). The HYPCON trial (CTRI/2023/02/049804) tested to reduce 10 fractions of PORT by delivery of hypofractionated PORT. Methods: Patients of HNC after radical surgery, with intermediate risk factors, were randomized based on site, T and N stage to either standard fractionation arm A (60Gy/30 fractions/6 weeks) or hypofractionated arm B (50Gy/20 fractions/4 weeks) in a 1:2 manner. The minimum sample size for the study was estimated based on a non-inferiority trial design as 120 considering a 10% clinical effectiveness margin and 5% attrition. Treatment allocation was done based on T stage, N stage &amp; HNC subsite. Target delineation included tumour bed with adequate margins (CTV_P) and microscopic lymph nodal (CTV_N) basin at risk. Organ delineation included all DARS. A double arc swallowing-sparing IMRT was used in both arms. The primary endpoint was locoregional control (LRC) at 1 year. Compliance, RT time (RTT), overall treatment time (OTT), progression-free survival (PFS) and overall survival (OS) were calculated in all patients. Acute &amp; late toxicities were recorded as per RTOG scale. Results: 135 patients were enrolled, 45 in Arm A &amp; 90 in Arm B. Majority of patients (96.9%) had oral cavity primary. Most of patients 74.8 % had early-stage disease. Compliance to PORT was 91.1% in Arm A versus 100% in Arm B. Median RTT for Arm A was 43 days (25-73 days) and 28 days (25-43 days) for Arm B (p&lt;0.0001). Median OTT in Arm A was 91 days (70-126 days) and 77 days (57-119 days) in Arm B (p&lt;0.0001). Median follow-up was 12.7 (2.73-23.87) months. One year, LRC was 72.9% vs 91.6% (p=0.007); PFS was 70.6% vs 90.5% (p=0.009) and OS was 88.7% vs 94.5% (p 0.02) Arm A versus Arm B respectively. Grade 3 or higher acute toxicity was seen in 39% in Arm A and 31.1% in Arm B (p=0.374). Grade 3 or higher late toxicity events were noted in 29.2% and 32.2% in arms A and B respectively (p= 0.671). Conclusions: Hypofractionated PORT reduced RTT &amp; OTT and was associated with improved treatment compliance, treatment outcomes (LRC, PFS, OS), and similar acute and late toxicity profile. This is the first study to demonstrate the superiority of hypofractionated compared to conventional PORT delivery for HNC. Clinical trial information: CTRI/2023/02/049804 .

Hydroxyurea mobile directly observed therapy versus standard monitoring in patients with sickle cell anemia: a phase 2 randomized trial

BackgroundSickle cell anemia (SCA) prevalence remains high in sub-Saharan Africa. Long-term treatment with hydroxyurea (HU) increases survival, however, poor adherence to treatment could limit effectiveness. Whilst HU treatment adherence is currently high, this might decrease over time.MethodsWe conducted a single-center, randomized, open-label, parallel group phase 2 controlled clinical trial to determine whether mobile Directly Observed Therapy (m-DOT) increases HU treatment adherence (NCT02844673). Eligible participants were adults with homozygous SCA. People on a chronic blood transfusion program, with hemoglobin (Hb) A levels greater than 20% of the total Hb, total Hb less than 4 g/dL, pregnant or HIV positive were excluded. After a 3-month pre-treatment period participants were randomized to either m-DOT or standard monitoring arm. All participants received smart mobile phones and were treated with HU (15 mg/kg) daily for three months. In the m-DOT arm, drug intake was video recorded on cell phone by the participant and the video sent to the study team. The primary objective was to evaluate the effect of m-DOT on adherence to HU treatment by medication possession ratio (MPR).ResultsOf the 86 participants randomized, 76 completed the trial (26.13 ± 6.97 years, 63.5 % female). Adherence was high (MPR > 95 %) in both groups, 29 (80.6 %) in m-DOT versus 37 (94.9 %) in the standard monitoring arm (P = 0.079). No HU treatment was withheld from participants due to safety concerns.Conclusionsm-DOT did not increase adherence to HU treatment. We recommend that further testing in larger trials with a longer follow up period be undertaken.

Barbed suture in neck dissection: a randomized clinical study on efficacy, safety and aesthetic outcome

PurposeThe resection of lymph nodes/neck dissection is a typical part of the surgical treatment of head and neck malignancies. The aim of this study was to compare subcutaneous closure using single knotted, braided suture (VicrylTM, standard arm) with continuous self-locking, monofilament barbed suture (V-LocTM, experimental arm).MethodsNeck Lock was a randomized clinical trial at a single tertiary referral center. It was conducted from 2016 till 2022 with a follow-up period of 3 months. Assessment of safety and aesthetic outcome was double-blinded. 68 patients were randomized after application of exclusion criteria. Subcutaneous wound closure was performed in an intrapatient randomized fashion for suture technique. The primary endpoint was the duration of subcutaneous sutures. Wound healing and scar formation were recorded at multiple postoperative intervals as secondary endpoints.ResultsThe median age was 61 years, 89.7% were male. 92.6% suffered from a squamous cell carcinoma. There was a significant difference in median subcutaneous suture time (p = 0.024) between the experimental (6:11 ± 2:30 min) and standard (7:01 ± 2.42 min) arms. There was no significant difference in safety when assessing adverse events (AEs). At least one AE occurred in 14.7% vs. 5.9%, for barbed and smooth sutures respectively (p = 0.16).ConclusionFor neck dissection of head and neck malignancies, subcutaneous wound closure with self-locking sutures offers significant time savings over the single knot technique with similar safety and aesthetic results.Trial registration informationThe trial was registered with WHO acknowledged primary registry “German Clinical Trials Register” under the ID DRKS00025831 (https://drks.de/search/de/trial/DRKS00025831).

A multicenter randomized controlled trial comparing three-times-a-day intermittent enteral postural feeding to continuous enteral feeding among mechanically ventilated patients in intensive care

BACKGROUND AND AIMSPrevious randomized controlled trials (RCTs) comparing intermittent feeding versus continuous feeding used different methods, employed shorter fasting intervals, ignored patients’ posture in bed during feeds, and showed mixed results. Prolonged fasting intervals are hypothesized to have several benefits. Additionally, there is evidence for more efficient gastric emptying in the right lateral position. In this multicenter RCT, we aimed to compare the effects of three-times-a-day gastric feeding while in the right lateral tilt position (intermittent postural feeding) versus standard continuous gastric feeding (standard feeding) on gastrointestinal intolerance and mortality among mechanically ventilated patients in ICU. METHODSAdult ICU patients with gastric feeding tube in-situ and requiring invasive mechanical ventilation were randomized to either intermittent postural feeding group or to the standard feeding group. The feeding formula, target daily feed volume and posture turns were determined as per standard practice for all patients. Primary outcome was an incidence rate per 100 patient-days of gastrointestinal intolerance, a composite outcome of vomiting, diarrhea or constipation. Secondary outcomes were all-cause hospital mortality, gastrointestinal intolerance-free days, ventilator-free days, episodes of vomiting or diarrhea per patient, and mean diet volume ratio (diet received/ diet prescribed). RESULTSAt five multidisciplinary ICUs, 120 mechanically ventilated, adult ICU patients (median age 65 years, 60% males) were randomly allocated to intermittent postural feeding (n=61) and standard feeding (n=59). The primary outcome did not differ between intermittent feeding arm versus standard arm (8.5, 95% confidence interval (CI): 5.9-11.8, versus 6.2, 95% CI: 4.1-9.1 per 100 patient-days; p =0.23). Gastrointestinal intolerance-free days until day 14 were similar (6 [2-8] versus 5 [2-10]; p =0.68) in both groups. Number of episodes per patient of vomiting, diarrhea, or constipation also did not differ in between groups. All-cause hospital mortality between intermittent feeding arm versus standard arm was 20% versus 31% (p=0.17). There were no significant between-group differences in any of the other secondary outcomes. CONCLUSIONSIntermittent gastric feeds delivered three-times-a-day while in the right lateral tilt position among mechanically ventilated patients was as well tolerated as the continuous enteral feeding. A definitive RCT to assess other clinically important outcomes is justified. Trial registrationACTRN12616000212459 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365526&isReview=true