Pilot Study Research Articles

Impact of early continuous positive airway pressure in the delivery room (DR-CPAP) on neonates < 1500 g in a low-resource setting: a protocol for a pilot feasibility and acceptability randomized controlled trial

BackgroundPreterm birth is the leading cause of childhood mortality, and respiratory distress syndrome is the predominant cause of these deaths. Early continuous positive airway pressure is effective in high-resource settings, reducing the rate of continuous positive airway pressure failure, and the need for mechanical ventilation and surfactant. However, most deaths in preterm infants occur in low-resource settings without access to mechanical ventilation or surfactant. We hypothesize that in such settings, early continuous positive airway pressure will reduce the rate of failure and therefore preterm mortality.MethodsThis is a mixed methods feasibility and acceptability, single-center pilot randomized control trial of early continuous positive airway pressure among infants with birthweight 800–1500 g. There are two parallel arms: (i) application of continuous positive airway pressure; with optional oxygen when indicated; applied in the delivery room within 15 min of birth; transitioning to bubble continuous positive airway pressure after admission to the neonatal unit if Downes Score ≥ 4 (intervention), (ii) supplementary oxygen at delivery when indicated; transitioning to bubble continuous positive airways pressure after admission to the neonatal unit if Downes Score ≥ 4 (control). A two-stage consent process (verbal consent during labor, followed by full written consent within 24 h of birth) and a low-cost third-party allocation process for randomization will be piloted.We will use focus group discussions and key informant interviews to explore the acceptability of the intervention, two-stage consent process, and trial design. We will interview healthcare workers, mothers, and caregivers of preterm infants. Feasibility will be assessed by the proportion of infants randomized within 15 min of delivery; the proportion of infants in the intervention arm receiving CPAP within 15 min of delivery; and the proportion of infants with primary and secondary outcomes measured successfully.DiscussionThis pilot trial will enhance our understanding of methods and techniques that can enable emergency neonatal research to be carried out effectively, affordably, and acceptably in low-resource settings. This mixed-methods approach will allow a comprehensive exploration of parental and healthcare worker perceptions, experiences, and acceptance of the intervention and trial design.Trial registrationThe study is registered on the Pan African Clinical Trials Registry (PACTR) PACTR202208462613789. Registered 08 August 2022. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23888.

Association between bone microarchitecture and sarcopenia in postmenopausal women with type 2 diabetes.

Type 2 diabetes (T2D) increases the risk of sarcopenia, which independently contributes to bone fragility. We aimed to explore the association between sarcopenia/sarcopenic obesity and bone quality using second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) in T2D. We analyzed the baseline participant characteristics of an ongoing randomized clinical pilot trial (CTRI/2022/02/039978). Postmenopausal women (≥ 50years) with T2D and high risk of fragility fractures were included. Areal BMD (aBMD), trabecular bone score (TBS), and body composition were measured using DXA. Bone microarchitecture was assessed at distal radius/distal tibia using HR-pQCT. Muscle strength was estimated using dominant handgrip strength (HGS). Sarcopenia was defined as low HGS (< 18.0kg) and low appendicular skeletal muscle index (ASMI) (< 4.61kg/m2). Probable sarcopenia was defined as low HGS with normal ASMI. Sarcopenic obesity was classified as co-existence of sarcopenia and obesity (BMI ≥ 25.0kg/m2). We recruited 129 postmenopausal women (mean age 64.2 ± 6.7years). Participants were categorized into four mutually exclusive groups: group A (normal HGS and ASMI, n = 17), group B (probable sarcopenia, n = 77), group C (non-obese sarcopenia, n = 18), and group D (obesesarcopenia, n = 18). The four groups did not differ significantly with regard to baseline characteristics, fracture prevalence, HbA1c, aBMD, and TBS. However, HR-pQCT-derived volumetric BMD and cortical/trabecular microarchitecture were significantly poorer in group C/group D than in group A/group B. Bone quality rather than bone density (quantity) is adversely affected in T2D postmenopausal women with sarcopenia/sarcopenic obesity, which could increase the fracture risk in this patient sub-population.

Three-outcome designs for external pilot trials with progression criteria

BackgroundWhether or not to progress from a pilot study to a definitive trial is often guided by pre-specified quantitative progression criteria with three possible outcomes. Although the choice of these progression criteria will help to determine the statistical properties of the pilot trial, there is a lack of research examining how they, or the pilot sample size, should be determined.MethodsWe review three-outcome trial designs originally proposed in the phase II oncology setting and extend these to the case of external pilots, proposing a unified framework based on univariate hypothesis tests and the control of frequentist error rates. We apply this framework to an example and compare against a simple two-outcome alternative.ResultsWe find that three-outcome designs can be used in the pilot setting, although they are not generally more efficient than simpler two-outcome alternatives. We show that three-outcome designs can help allow for other sources of information or other stakeholders to feed into progression decisions in the event of a borderline result, but this will come at the cost of a larger pilot sample size than the two-outcome case. We also show that three-outcome designs can be used to allow adjustments to be made to the intervention or trial design before commencing the definitive trial, providing the effect of the adjustment can be accurately predicted at the pilot design stage. An R package, tout, is provided to optimise progression criteria and pilot sample size.ConclusionsThe proposed three-outcome framework provides a way to optimise pilot trial progression criteria and sample size in a way that leads to desired operating characteristics. It can be applied whether or not an adjustment following the pilot trial is anticipated, but will generally lead to larger sample size requirements than simpler two-outcome alternatives.

Impact of mini-dose dexmedetomidine supplemented analgesia on sleep structure in patients at high risk of obstructive sleep apnea: a pilot trial.

Obstructive sleep apnea (OSA) is common in surgical patients and associated with worse perioperative outcomes. To investigate the effect of mini-dose dexmedetomidine supplemented analgesia on postoperative sleep quality pattern in patients at high risk of OSA. A pilot randomized, double-blind, placebo-controlled trial. A tertiary university hospital in Beijing, China. One hundred and fifty-two adult patients who had a STOP-Bang score ≥3 and a serum bicarbonate level ≥28 mmol/L and were scheduled for major noncardiac surgery between 29 January 2021 and 20 September 2022. After surgery, patients were provided with high-flow nasal cannula and randomized in a 1:1 ratio to receive self-controlled opioid analgesia supplemented with either mini-dose dexmedetomidine (median 0.02 μg/kg/h) or placebo. We monitored polysomnogram from 9:00 pm to 6:00 am during the first night. Our primary outcome was the percentage of stage 2 non-rapid eye movement (N2) sleep. Secondary and exploratory outcomes included other postoperative sleep structure parameters, sleep-respiratory parameters, and subjective sleep quality (Richards-Campbell Sleep Questionnaire; 0-100 score range, higher score better). All 152 patients were included in intention-to-treat analysis; 123 patients were included in sleep structure analysis. Mini-dose dexmedetomidine supplemented analgesia increased the percentage of stage N2 sleep (median difference, 10%; 95% CI, 1 to 21%; p = 0.029); it also decreased the percentage of stage N1 sleep (median difference, -10%; 95% CI, -20% to -1%; p = 0.042). Other sleep structure and sleep-respiratory parameters did not differ significantly between the two groups. Subjective sleep quality was slightly improved with dexmedetomidine on the night of surgery, but not statistically significant (median difference, 6; 95% CI, 0 to 13; p = 0.060). Adverse events were similar between groups. Among patients at high risk of OSA who underwent noncardiac surgery, mini-dose dexmedetomidine supplemented analgesia may improve sleep quality without increasing adverse events. Clinicaltrials.gov, identifier NCT04608331.

Quality and completeness of, and spin in reporting of, pilot and feasibility studies in hip and knee arthroplasty: a protocol for a methodological survey

IntroductionPilot or feasibility trials examine the feasibility, viability and recruitment potential of larger, main trials. Specifically, a pilot trial can be instrumental in identifying methodological issues essential to the development...

Social Control and Health Behaviors Among Individuals Living with Parkinson's Disease: A Pilot Study.

Positive health behaviors (e.g., exercise, healthy eating habits, good sleep hygiene, treatment adherence) are important in ensuring optimal symptom management and health outcomes among individuals living with Parkinson's disease (PD). While multiple factors may influence engagement in health behaviors, little is known about the occurrence of social control, or relationship partners' attempts to influence and regulate another's behavior, and its potential role in the adoption of health behaviors among individuals with PD. To better understand the types of social control attempts employed and begin to explore the association between social control attempts and behavioral responses (e.g., engage in the targeted health behavior, hide the behavior) to those attempts, survey data were drawn from a cross-sectional, pilot study of married/partnered Veterans diagnosed with idiopathic PD (n = 25). Participants completed self-reported measures of sociodemographics, physical and mental well-being, relationship functioning, and both the frequency of and behavioral responses to positive and negative social control attempts. Although the majority of individuals reported their partners engaged in positive social control attempts, half also reported negative attempts. Bivariate analyses revealed more frequent positive social control attempts from one's partner were related to both positive and negative behavioral responses, and negative social control attempts were related to negative behavioral responses. However, when adjusting for covariates, positive social control attempts were related to positive behavioral responses, while negative social exchanges with one's partner (e.g., general conflict), rather than exposure to negative social control attempts, were related to negative behavioral responses. Findings lend preliminary evidence of the relationship between social control and exchanges and health behavior that may inform future, adequately powered observational and intervention studies that target interpersonal processes and health behaviors among individuals living with PD and their relationship partners.

Evaluation of Blood Lactate among Different Player Roles: A Pilot Study on Competitive Young Male Soccer Players.

Soccer match requires anaerobic and aerobic energetic metabolism. The aim of this pilot study was to investigate the changes in blood lactate concentration in young male soccer players in different playing roles at different time points after the soccer match. Following an initial screening of 134 young soccer athletes, 8 male athletes (average age of 15.5 ± 5 SD) were chosen for their characteristics similar to those of competitive athletes. Players were categorized as goalkeeper, central defender, central midfielder, and forward. Blood lactate concentrations were determined using a portable device at different times (10 min, 5 and 16 h) after the soccer match by a maximum effort test on a treadmill. The data were analyzed by one-way analysis of variance ANOVA, followed by Bonferroni's post-hoc test. The following results (mean ± SD) were obtained: VO2max (%) 60.33 ± 3.10; blood lactate (mM) end match (10 min) 2.17 ± 0.78, post-match-early (after 5 h) 2.2 ± 0.42, postmatch-late (16 h) 3.2 ± 0.84. ANOVA analysis indicated that the blood LA concentrations at end-match (10 min) and post-match-early (5 h) were statistically significative lower than those determined at post-match-late (16 h) (p < 0.05). These results suggest that aerobic mechanisms can also use LA as an energy source, contributing to the reduction of its blood concentration. This effect can be due to reduced maximal work during a soccer match and to the LA removal during exercise at reduced intensity. These data can provide indications for planning suitable training strategies for young male soccer players.

Personalized Food Avoidance Dietary Approach for Psoriasis and Hypertension: A Case Study and Pilot Trial

Background: The comorbidity, coheritability and common immune pathways of the inflammatory ‘chronic’ (non-communicable) diseases, suggest a shared aetiopathogenic mechanism, with phenotypic localization dependent on genetic predisposition, for example, the arteries in hypertension and the skin in psoriasis. Lifelong observation of psoriasis suggests genetically predisposed toxicity of amphiphilic fats, flavor enhancers, and nonsugar sweeteners. Aim: To conduct trials of personalized dietary intervention to abate the phenotypic expression of psoriasis and hypertension. Materials and Methods: The interventional case study of psoriasis was conducted by means of repetitive dietary challenge and avoidance testing. We then conducted an open trial of personalized nutrition on nine consenting recruits with uncomplicated essential hypertension. They were counseled on which foods to avoid or to take based on the experience gained in psoriasis. Study participants with ‘GOOD’ or ‘FAIR/POOR’ dietary compliance were compared with regard to blood pressure (BP) control, antihypertensive drug treatment requirement (ADTR), and anthropometry. Results: Data from four FAIR/POOR diet compliers and three GOOD compliers, as at 29 weeks of dietary intervention, showed mean systolic home BP values of 128.1 (±6.74) mmHg and 122.3 (±2.03) mmHg, respectively; the mean systolic automated office BP values were 139.8 (±8.80) mmHg and 108.3 (±5.55) mmHg, respectively; as at 39 weeks of dietary intervention, the mean ADTR scores were 4.2 (±2.12) and 1.03 (±0.57), respectively. Using data at baseline and from all available timepoints after dietary intervention, two-way ANOVA confirmed highly significant improvement of BP control (P &lt; 0.0001) and reduction of ADTR score (P = 0.0008) in GOOD compliers. GOOD compliers exhibited significantly more reductions in BMI, abdominal circumference, and triceps skinfold thickness than FAIR/POOR compliers (two-way ANOVA and linear regression: P &lt; 0.05). Conclusion: These results support the case for adverse dietary exposure avoidance to abate the phenotypic expression of chronic disease.

476 The Supra-Short Ultrasound Protocol to Assess for Rotator Cuff Tears in the Emergency Department: A Pilot Trial

476 The Supra-Short Ultrasound Protocol to Assess for Rotator Cuff Tears in the Emergency Department: A Pilot Trial

TCT-582 Evaluation of LVEDP Change During High-Risk PCI With and Without Impella Support (ELVIS): A Pilot Trial

TCT-582 Evaluation of LVEDP Change During High-Risk PCI With and Without Impella Support (ELVIS): A Pilot Trial

Exercise During Neoadjuvant Chemoradiation Treatment To Improve Rectal And Esophageal Cancer Outcome (EXENTRO) Pilot Trial

Exercise During Neoadjuvant Chemoradiation Treatment To Improve Rectal And Esophageal Cancer Outcome (EXENTRO) Pilot Trial

Risk Factors for COVID-19 Mortality in Epidemic Treatment Centers: A Case-Control Study from Decentralized Regions of Senegal

Introduction: The COVID-19 pandemic is an emerging viral zoonosis caused by SARS-CoV2. It is responsible for a systemic infection in humans, primarily respiratory. In Senegal, the Thiès Region confirmed its first case on March 14, 2020. The second epidemic wave occurring in 2021 was marked by high fatality, justifying our study on the factors associated with deaths among COVID-19 patients hospitalized at the Epidemic Treatment Centers (CTE) of the Regional Health Directorate of Thiès (Senegal). Patients and Methods: Unmatched case-control study, 1 case to 2 controls, relating to COVID-19 deaths recorded in the Thiès Regional Health Directorate from January 1 to December 31, 2021. All patients who tested positive for COVID-19 (PCR/Antigenic test) hospitalized in CTEs were included. All confirmed COVID-19 patients who died were referred to as “cases,” and all recovered patients as “controls.” The sampling of deaths was exhaustive, standardized sociodemographic, clinical, therapeutic and evolutionary data collected from patient files after a pilot trial with quality control. The data was entered on kobo collect and analyzed on Epi info7. Quantitative variables (mean, standard deviation) and qualitative variables (proportions. Measures: odds ratio, chi2 or Fisher exact test, significance threshold set at p&lt;0.05) were used. Results: A total of 348 patients were recruited in this study including 116 deaths and 232 recovered, the average age was 68.9 years +/- 14.24 for the deceased patients compared to 61.5 +/- 14.24 for the recovered, with male predominance in both groups. The most common clinical signs (cases/controls) were dyspnea (98.3/84.49%), fever (71.5/68.1%), asthenia (57.8/65.4%). and cough (52.6/58.1%). Complications were dominated by acute respiratory distress (87.9/3.8%), (11.2%/0.4%) and pulmonary embolism (03.5/0%). The factors associated with deaths found after multivariate analysis by logistic regression were male sex (OR: 4.11, 95% CI : 1.45 – 11.61 and p = 0.0076), patients aged over 60 years (OR=1.77, 95% CI: 1.0018-3.1438, p=0.049), complications such as stroke (OR=31.00; 95% CI: 5.69-168.73 and p=0 .0001), shock (OR22.61; 95% CI: 1.44-353.67 and p=0.026) and acute respiratory distress syndrome (OR: 204.09 95% CI : 70.44-591.30 and p = 0.000). Conclusion: The factors associated with COVID-19 deaths in the CTEs of Thiès Region are age, male gender, the presence of complications; stroke in particular, the state of Shock and ARDS.

Quantum Imitation Learning.

Despite remarkable successes in solving various complex decision-making tasks, training an imitation learning (IL) algorithm with deep neural networks (DNNs) suffers from the high-computational burden. In this work, we propose quantum IL (QIL) with a hope to utilize quantum advantage to speed up IL. Concretely, we develop two QIL algorithms: quantum behavioral cloning (Q-BC) and quantum generative adversarial IL (Q-GAIL). Q-BC is trained with a negative log-likelihood (NLL) loss in an offline manner that suits extensive expert data cases, whereas Q-GAIL works in an inverse reinforcement learning (IRL) scheme, which is online, on-policy, and is suitable for limited expert data cases. For both QIL algorithms, we adopt variational quantum circuits (VQCs) in place of DNNs for representing policies, which are modified with data reuploading and scaling parameters to enhance the expressivity. We first encode classical data into quantum states as inputs, then perform VQCs, and finally measure quantum outputs to obtain control signals of agents. Experiment results demonstrate that both Q-BC and Q-GAIL can achieve comparable performance compared to classical counterparts, with the potential of quantum speedup. To our knowledge, we are the first to propose the concept of QIL and conduct pilot studies, which paves the way for the quantum era.

Effects of Mobile Application-Based Cognitive Behavioral Therapy on Psychological Outcomes in Women Treated for Breast Cancer: A Randomized Controlled Pilot Trial in Germany.

Breast cancer has a strong impact on the mental state of those affected. Cognitive behavioral therapy (CBT) is one effective approach to reduce disease burden. This randomized controlled pilot trial aimed to assess the effect of the digital CBT-based application Living Well on psychological outcomes in a German female breast cancer population. Female breast cancer patients (n=70) with ongoing or finished oncological treatment that is who were receiving or had received any type of oncological treatment were included in the study and randomized to an intervention group (IG, n=32) receiving Living Well in addition to care as usual, and a control group (CG, n=38) receiving care as usual only. Participants completed standardized questionnaires at baseline and after 2, 4, 8, and 12weeks to assess anxiety and depression (HADS) as primary outcomes, distress (DT), health-related quality of life (HRQoL, AQoL-8D), and illness perception (B-IPQ) as secondary outcomes. After 12weeks, significant (p<0.05) higher improvements in the IG could be observed in anxiety levels, HRQoL, and illness perception, when compared to the CG. Age and time since diagnosis were found to be relevant covariates for anxiety levels. In distress levels, the IG showed a clinically relevant and nearly significant reduction compared to the CG (p=0.057). No effects could be observed in depression levels. The results demonstrate the potential of Living Well to improve psychological outcomes of female breast cancer patients and encourage further studies evaluating the effectiveness of the digital application. The trial has been registered in the German Clinical Trials Register (DRKS00029918).

A pilot trial of an LGBTQ-affirmative cognitive-behavioral therapy for transgender and gender expansive individuals’ mental, behavioral, and sexual health

Transgender and gender expansive (TGE) individuals face minority stress and associated health risks, especially in high-stigma contexts. LGBTQ-affirmative cognitive-behavioral therapy (CBT) is one of the only evidence-based interventions developed to address minority stress to improve psychosocial health. Yet, trials of this treatment have mostly enrolled cisgender sexual minorities, TGE youth, and those living in North American contexts. This study tested the feasibility, acceptability, and preliminary efficacy of LGBTQ-affirmative CBT for TGE adults living in the high-stigma context of Romania. Twenty-five TGE individuals (Mage=25.16, SDage=6.39; 44% transgender women, 40% transgender men, 16% non-binary) reporting depression and/or anxiety symptoms received 16 virtual sessions of LGBTQ-affirmative CBT from trained psychologists. Assessments of mental (e.g., depression), behavioral (e.g., hazardous drinking), and sexual (e.g., HIV-transmission risk behavior) health outcomes, and minority stress and universal risk mechanisms were administered at baseline and 5-month follow-up. Results showed reductions in depression and anxiety symptoms and certain minority stress (e.g., anticipated stigma, identity concealment) and universal risk (e.g., unassertiveness) mechanisms from baseline to follow-up. The intervention was highly feasible (e.g., timely recruitment, high session attendance), and exit interviews revealed high acceptability in terms of the treatment’s relevance, goals, imparting minority stress knowledge and identity-related hope and acceptance, format, and therapeutic alliance. LGBTQ-affirmative CBT shows feasibility, acceptability, and preliminary efficacy among TGE individuals living in Romania, with promise for other high-stigma contexts. Future randomized controlled trials and reductions in structural determinants remain priorities.

Parent Facilitation of Condom Access and HIV Testing Associated with Improved Sexual Health Outcomes for Sexual Minority Young Men.

Sexual minority young men experience a high HIV incidence. Parent-based interventions are promising for prevention efforts, but further research is needed to identify specific, replicable parental behaviors associated with improved sexual health outcomes for sexual minority young men. We assessed parental behaviors in the domains of facilitating access to condoms, providing instruction in condom use, and supporting HIV testing, and tested whether parental behaviors were associated with sons' condom use self-efficacy and intentions to get tested for HIV. Data came from the baseline assessment of a pilot trial of a parent-based HIV prevention program, and participants were dyads (n = 61) of sexual minority young men (M. age: 16.87; 46% racial/ethnic minority) and their parents (M. age: 44.31; 26% racial/ethnic minority). Parents and sons reported on parental behaviors in each domain. Results indicated that parents' facilitation of access to condoms was associated with sons' condom use self-efficacy, and parents' facilitation of HIV testing was associated with sons' HIV testing intentions. Findings were robust across both parent and son reports of parental behaviors. Parental condom use instruction was unrelated to sons' condom use self-efficacy. Findings suggest that parent-based HIV prevention programs for sexual minority young men should encourage parents to provide instrumental assistance to their sons in accessing condoms and HIV testing. There is a need for further research to identify underlying mechanisms.

Leveraging Mobile Health to Improve Capecitabine Adherence Among Women With Breast Cancer: A Pilot Randomized Controlled Trial.

Oral capecitabine improves convenience compared to intravenous therapies but presents monitoring challenges. We conducted a randomized pilot trial to evaluate a mobile health intervention to remotely monitor capecitabine adherence and patient-reported outcomes (PROs) among women with breast cancer. Patients with breast cancer prescribed capecitabine, an oral chemotherapy with a complex, cyclical regimen, were randomly assigned to enhanced usual care (EUC) or PRO arm. Participants were asked to use a smart pill bottle to measure adherence (timing and dose) and complete baseline and 90-day follow-up surveys. PRO participants received text messages for missed or incorrect doses and weekly text-based symptom assessments, and their oncologists received alerts for severe symptoms or missed doses. We compared nonadherence (<80%) and changes from enrollment to follow-up on reported physical and mental health quality-of-life scores and number of severe symptoms by study arm. Overall, 32 women were randomly assigned (17 EUC and 15 PRO): 28 (87.5%) received the intervention and 24 (78.1%) completed the follow-up survey. Among participants who received the intervention, PRO participants responded to 83.3% of symptom questions; 7.7% of PRO participants were nonadherent compared with 40.0% of EUC participants (P = .049). Among those who completed the follow-up survey, 12.5% of PRO participants had reductions in their mental health composite scores compared with 69.2% of EUC participants (P = .011); 10% of PRO participants had more severe symptoms at follow-up compared with 57.1% of EUC participants (P = .019). A mobile health intervention using text message reminders and symptom assessments improved medication adherence and mental health quality-of-life scores and lowered symptom burden of patients with breast cancer prescribed capecitabine. Future work should evaluate the longer-term impacts of this intervention.

Pegloticase-Induced Rapid Uric Acid Lowering and Kidney and Cardiac Health Markers in Youth-Onset Type 2 Diabetes: A Pilot Clinical Trial

Rationale & ObjectiveElevated serum uric acid (SUA) is a risk factor for incident hypertension and diabetic kidney disease in young persons with type 2 diabetes (T2D), particularly men. The acute benefit of aggressively lowering SUA on kidney and cardiovascular function in this population remains underexplored. This study was conducted to investigate the impact of a single pegloticase infusion on kidney and cardiovascular function. Study DesignAn open-label pilot trial. Setting & ParticipantsThe study involved 10 young adult males with youth-onset T2D and SUA levels ≥5 mg/dL. Intervention(s)Participants received a single infusion of pegloticase (8 mg). Evaluations were conducted using iohexol-based measured glomerular filtration rate (mGFR) and cardiac/kidney MRI before and one week after infusion. OutcomesThe primary outcomes were changes in SUA and mGFR one week after pegloticase infusion. ResultsNine participants (mean [±SD] age 22±5 years, HbA1c 8.6±3.3%, BMI 40.1±11.0 kg/m2, SUA 6.7±1.1 mg/dL) completed the pegloticase infusion and were included in the analysis. One week after the infusion, median [p25,p75] SUA concentrations dropped from 6.4 [5.6,7.6] to 0.5 [0.5,4.6] mg/dL (p=0.01). Mean mGFR increased from 113±20 to 122±19 ml/min per 1.73 m2 (p=0.004). Among responders (SUA reduction ≥3 mg/dL), an increase in mGFR correlated with an increase in renal artery blood flow (r:0.60, p=0.24) and decrease in SUA (r:-0.79, p=0.05). Mean MRI peak longitudinal cardiac strain additionally decreased from 15.4±2.2 to 13.1±2.2 % (p=0.03) in these responders. LimitationsThe pilot nature of the study and the small sample size limit the generalizability of the findings. ConclusionsIn young adult males with T2D, a single pegloticase infusion decreased SUA levels, which increased mGFR and was strongly associated with increased renal blood flow and impaired cardiac global longitudinal strain. Further research is required to assess the long-term efficacy and safety of pegloticase in patients with T2D.

Closed-loop neural interfaces for pain: Where do we stand?

Advances in closed-loop neural interfaces and neuromodulation have offered a potentially effective and non-addictive treatment for chronic pain. These interfaces link neural sensors with device outputs to provide temporally precise stimulation. We discuss challenges and trends of state-of-the-art neural interfaces for treating pain in animal models and human pilot trials.

Intensive Home Blood Pressure Lowering in Patients with Advanced CKD

Optimal blood pressure (BP) targets in advanced CKD are controversial. More intensive BP lowering in the setting of advanced CKD is thought to be associated with risk of acute kidney injury, hyperkalemia, and ESKD. We aimed to conduct a pilot trial of intensive BP control to determine if lower SBP targets can be safely achieved for patients with CKD through titration of BP medications using in-home measured BP. Non-blinded randomized controlled trial. 108 patients with advanced CKD (eGFR ≤30 mL/min/1.73 m2) and hypertension. Participants were randomized either to a target home SBP goal of <120 mmHg (N=66) or a less intensive SBP goal (N=42). Antihypertensive medications were titrated to achieve the target home SBP range in the first 4 months of the study and maintained until the end of the study. Home BP was measured using a wireless Bluetooth-enabled monitor that transmitted readings to providers in real-time. The primary efficacy outcome was the difference in achieved clinic SBP between the two study arms from months 4-12. Safety outcomes included hyperkalemia, a composite outcome of falls or syncope, and onset of need for dialysis or kidney transplantation. The mean clinic SBP at month 12 was 124.7 mmHg in the intensive SBP group vs. 138.2 mmHg in the less intensive SBP group. Averaged over months 4-12, the achieved mean clinic SBP in the intensive SBP arm was 11.7 mmHg (95% CI 7.5 to 16 mmHg, p<0.001) lower than the mean SBP achieved in the less intensive SBP arm. Primary safety outcomes were not statistically significantly different between the two arms (all p>0.05). Small sample size which may limit our ability to detect clinically significant differences in rates of adverse outcomes; single-center design. A clinic SBP goal of <120 mmHg is feasible to achieve with the help of real-time home BP monitoring and appears to be safe in this study population with advanced CKD. Larger trials to determine optimal BP targets in advanced CKD and the risks and benefits associated with more intensive BP control are warranted.