Future Randomized Controlled Trials Research Articles

Self-care Practices of Patients With Heart Failure Using Wearable Electronic Devices: A Systematic Review.

Heart failure (HF) is the fastest growing cardiovascular condition globally; associated management costs and hospitalizations place an immense burden on healthcare systems. Wearable electronic devices (WEDs) may be useful tools to enhance HF management and mitigate negative health outcomes. We aimed to perform a systematic review to examine the potential of WEDs to support HF self-care in ambulatory patients at home. Five databases were searched for studies published between 2007 and May 2022, including OVID MEDLINE, EMBASE (OVID), APA PsycINFO (OVID), Cochrane Central Register of Controlled Trials (OVID), and CINAHL Plus with Full Text (Ebsco). After 6210 duplicates were removed, 4045 records were screened and 6 were included for review (2 conference abstracts and 4 full-text citations). All studies used WEDs as 1 component of a larger intervention. Outcome measures included quality of life, physical activity, self-efficacy, self-care, functional status, time to readmission, social isolation, and mood. Studies were of moderate to high quality and mixed findings were reported. Enhanced exercise habits and motivational behavior to exercise, as well as decreased adverse symptoms of fatigue and dyspnea, were identified in 2 studies. However, improvements in exercise capacity and increased motivational behavior did not lead to exercise adherence in another 2 studies. The findings from this review suggest that WEDs may be a viable health behavior improvement strategy for patients with HF. However, studies of higher quality, with the primary intervention being a WED, and consistent outcome measures are needed to replicate the positive findings of studies identified in this review.

MIRA Rehab Exergames for Older Male Residents in a Care Home Center in Saudi Arabia: Protocol for a Feasibility Randomized Controlled Trial.

Physical activity leads to improvements in morbidity, mortality, and quality of life, especially when it is progressive, challenging, and regular. There is strong evidence that strength and balance exercises decrease the risk of falling. However, traditional exercises may be tedious and not very motivating for participants. Exergames have been found to increase engagement and enjoyment for older users. This study will conduct a feasibility randomized controlled trial (RCT) on the use of MIRA Rehab Exergames among older male residents in a care home setting in Saudi Arabia. A sample of 30 eligible participants will be recruited to meet feasibility study requirements. We will recruit 38 residents in the care home who will be randomly allocated to either an intervention or a control group. The intervention participants will perform gamified exercises using the MIRA telerehabilitation platform (30 minutes 3 times per week for 6 weeks). The control group will receive educational advice based on booklets of the Otago exercise program and be encouraged to exercise (30 minutes 3 times per week for 6 weeks). Participants will be assessed at weeks 0, 6, and 12. Assessments will include feasibility measures (eligibility, recruitment and attrition rates, and practicalities of data collection methods) and participant outcome measures (balance, strength, mobility, adherence, quality of life, fear of falling, depression, acceptability, and usability). Data collection started in November 2021 and ended in March 2022. The study is currently in the data analysis stage, which commenced in May 2022. The findings from this feasibility RCT will be used to design a definitive RCT to test whether the MIRA Rehab Exergame program benefits older people in Saudi Arabia who may not like participating in traditional exercise programs and may be unwilling or unable to leave their homes. This study will contribute to our understanding of how to recruit in this specific population and provide information to inform the design of a future RCT. DERR1-10.2196/39148.

Racial and Ethnic Disparities in Androgenetic Alopecia Clinical Trials in the United States

Introduction: Androgenetic alopecia (AGA) is the most common type of hair loss worldwide and is estimated to affect about 80 million people in the United States. Recent trends suggest that incidence and severity of the disease are increasing across all genders and races. Randomized controlled trials (RCTs) involving diverse patient populations are necessary to individualize treatment. Objective: Evaluate enrollment and subgroup analysis of people falling in racial/ethnic minority groups in phase II and III RCTs for AGA published in the United States within the past 10 years. Methods: We examined completed published phase II and III randomized, double-blind, placebo-controlled trials investigating AGA. Race/ethnicity data was extracted for each RCT using US Census Bureau guidelines. Results: 20 total RCTs with a total of 1855 participants were included in the analysis. 8 (40%) of RCTs included race/ethnicity data. Among these, 3 (15%) studies included only race and 5 (25%) included both. The majority of study patients were white (n= 862/1063, 81.1%) followed by African American (n=127/1063, 11.9%) and Asian (n=33/1063, 3.1%). Six (0.56%) patients identified as American Indian/Alaska Natives, 5 (0.47%) as Hawaiian/Pacific Islander, and 16 (1.5%) as another race or race was unknown. Ethnicity was reported in 5 (25%) of trials, totaling 317 participants; 60 (18.9%) patients identified as Hispanic. Conclusions: Non-Caucasian patients remain underrepresented in RCTs despite AGA being a highly prevalent condition, reducing the generalizability of trial outcomes to the general population. Future RCTs should update definitions of race/ethnicity and include more diversity among AGA patients.

Investigating changes in cognition associated with the use of CPAP in cognitive impairment and dementia: A retrospective study

Study objectivesTo characterize the impact of CPAP use on cognition in a clinical cohort with obstructive sleep apnea (OSA) and cognitive impairment due to neurodegenerative or vascular etiologies after controlling for baseline sleepiness. MethodsWe retrospectively analyzed data from 171 patients with cognitive impairment and an OSA diagnosis confirmed with in-laboratory polysomnography or home sleep apnea testing (mean age 69.8 ± 10.6; 66% male) who were eligible to use CPAP. Baseline and follow-up Epworth Sleepiness Score (ESS), Montreal Cognitive Assessment (MoCA), and Mini-Mental Status Examination (MMSE) were obtained from clinical and research visits conducted before and after CPAP initiation. Good CPAP adherence was defined as CPAP use ≥4 h/night, for 7 days/week at follow-up. Associations between CPAP adherence and follow-up cognitive scores were analyzed using multivariable linear mixed-effects models. ResultsAfter adjusting for age, sex, body mass index, baseline ESS, duration of CPAP therapy, relevant comorbidities and the random effect of research study cohort, good CPAP adherence (compared to poor CPAP adherence or no use of CPAP) for a duration of 2–12 months was associated with a 2.3-point (1.2–3.3 95% CI) higher follow-up MoCA score (p < 0.001) and a 1.2-point (0.3–2.3 95% CI) higher follow-up MMSE score (p = 0.01). ConclusionsIn patients with OSA and cognitive impairment due to a neurodegenerative or vascular etiology, use of CPAP is associated with improved cognitive outcomes. The findings of this study may aid in motivating patients to use CPAP and support future randomized controlled trials in this area.

Pilot Randomised, Double‐Blind, Placebo‐Controlled Crossover Trial Evaluating the Feasibility of an Intranasal Oxytocin in Improving Social Cognition in Individuals Living with Alzheimer’s Disease

AbstractBackgroundIndividuals living with Alzheimer’s disease (AD) demonstrate global deficits in social cognition. These deficits have been associated with impaired interpersonal relationships amongst caregivers, in turn contributing to a greater sense of caregiver ‘burden’. In other areas of neuropsychiatric disease (i.e., autism spectrum disorder), intranasal oxytocin (INOT) administration has shown replicable improvements in social cognitive function, particularly in Theory of Mind. Recently, randomised controlled trials (RCTs) in frontotemporal dementia have reported that repeated INOT administration may be regarded as safe and well tolerated at higher doses ‐ resulting in changes to apathy and improvements in empathic concern, as rated by a caregiver. To date, no studies have investigated the feasibility of an INOT treatment in individuals living with AD. Here, we conducted a pilot feasibility trial to determine the feasibility of recruitment, the acceptability of enrolment and the adherence to an INOT treatment in order to inform the subsequent design of a future RCT. Secondly, we sought to determine the effect size estimates on key potential social cognitive function outcome measures related to both the participant and their caregiver.MethodFour individuals living with AD were enrolled in a single‐centre, randomised, double‐blind, placebo‐controlled crossover trial involving a one‐week treatment period with both INOT (72 IU) and placebo.ResultAll participants reported no treatment‐causative or serious adverse events, following repeated INOT administration. While acceptability of enrolment was excellent (100%), as well as INOT treatment adherence (placebo, 95%; INOT, 98%), our feasibility of recruitment was not acceptable (i.e., only 7% of fifty‐eight individuals with dementia screened met inclusion criteria). However, positive/large effects were associated with expected secondary outcomes around self‐reported health and wellbeing, caregiver ‘burden’, intimacy and interpersonal bonding, following repeated INOT administration.ConclusionThese data provide the first evidence demonstrating the safety and tolerability of INOT administration in individuals living with AD. Despite limitations in sample size, moderate‐to‐large effect size improvements were identified in participant health outcomes as well as core social cognitive functions and burden as reported by a caregiver. This suggests potential broad‐ranging beneficial effects of INOT which should be assessed in future RCTs from multiple perspectives.

Insights into concepts, protocols, and evidence of surgery-first orthognathic approach-The journey so far

The aim of this narrative review was to comprehensively describe the surgery-first orthognathic approach (SFOA) or the surgery-first approach (SFA) in terms of the concept, procedure selection and evidence available to date. Comparisons with the conventional orthognathic surgery approach (COSA) are also made. In the light of newer advances in technology, including but not limited, to augmented reality - virtual treatment objective setup, 3D imaging, and computer-aided design and manufacturing (CAD/CAM), the “one patient two problems concept” needs to be thoroughly understood to further enhance both patients’ quality of life and practitioners’ clinical skills. Undoubtedly, gathering higher levels of evidence from future randomized control trials (RCTs) and developing standard core outcomes (COS) on SFOA are the need of the hour.

S20 Impact of Anxiety on Patients With IBD: Insights From the National Inpatient Database (NIS)- 2015-2019

Background: Inflammatory Bowel Disease (IBD) can have numerous complications involving all systems of the body. People with inflammatory bowel disease (IBD) are at increased risk of developing mental health disorders, such as anxiety. The aim of our study was to examine the impact of anxiety on the outcomes of patients with IBD. Methods: The Nationwide Inpatient Sample (NIS) database encompasses approximately 7 million inpatient hospitalizations annually in the United States. Data were extracted from the National Inpatient Sample (NIS) Database for the years 2015-2019. Patients aged 18 years and above with diagnoses of IBD and anxiety were identified using ICD codes. Multivariate regression analysis was used to estimate the odds ratios of in-hospital mortality, the average length of hospital stay (LOS), and hospital charges using STATA 17. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. Results: We identified 1,198,839 patients with IBD of which 235,880 patients were matched to those with anxiety. Average age was 52.04 years. There was a significant decrease in inpatient mortality (OR 0.56, CI 0.51-0.62, P < 0.0001) and total cost of hospitalization (-$3,242.13, CI -4,259.55 - -2224.70, P < 0.0001), but hospital length of stay increased (0.27 days, CI 0.20-0.34, P < 0.0001) between patients with IBD with cannabis use when compared to IBD patients without cannabis use. Conclusion(s): The different clinical manifestations and symptoms of IBD may cause several psychological changes in patients. Past studies demonstrated that psychological stress and disorders can trigger flares and relapses in patients with IBD. Our study showed that there was a statistically significant decrease in inpatient mortality and hospital LOS for patients with both IBD and anxiety compared to those with only IBD. Anxiety is known to be 2 to 3 times higher in patients with IBD, but it reduces morbidity and mortality. This may be due to the increased surveillance and treatment to this subgroup of patients. Given the known association between IBD and anxiety, clinicians be vigilant in detecting and treating concomitant anxiety as this could lead to better outcomes in this patient population, as our study revealed. Future randomized control trials are needed to further study the impact of anxiety on IBD.

Feasibility of a Hydrotherapy and Self-Management Education Program for Breast Cancer Patients with Shoulder Impairment

<h3>Research Objectives</h3> To evaluate the feasibility and acceptability of a multidimensional hydrotherapy and self-management education program for breast cancer patients. Secondary objectives were to explore change on shoulder disability measured by validated patient reported outcomes and therapist measured shoulder range of motion (ROM) and grip strength. <h3>Design</h3> This retrospective cohort study analyzed pre- and post-intervention data collected between January 2017 and March 2020. <h3>Setting</h3> Outpatient rehabilitation clinic in Toronto, Canada. <h3>Participants</h3> A total of 114 participants' charts were reviewed during the study period. Participant selection utilized a clinically referred sample of breast cancer patients with moderate to severe shoulder impairment and deemed medically fit to participate in aquatic based therapies. <h3>Interventions</h3> Six weekly, small group (n=3-7), supervised, hydrotherapy and educational sessions targeting shoulder mobility, scar management, lymphedema, and pain. <h3>Main Outcome Measures</h3> Feasibility was defined as ≥ 60% retention and ≥ 80% session attendance. Acceptability was defined as ≥ 80% satisfaction (≥ 4 on a 5 point Likert scale). <h3>Results</h3> A total of 88 (82.2%) participants attended at least 80% of the education sessions and 78 (76.5%) attended at least 80% of the aquatic sessions. 60 (96.8%) participants reported satisfaction with educational material; 44 (95.7%) reported satisfaction with hydrotherapy sessions. Statistically significant improvements were observed in DASH, SPADI, grip strength, and most ROM measures. <h3>Conclusions</h3> Combined hydrotherapy and self-management education appears to be a feasible and acceptable rehabilitation intervention for breast cancer survivors with shoulder impairment. While this could represent a potential adjunct to traditional land based therapies, future prospective randomized control trials are required to confirm causation and to explore the effect on functional outcome measures. <h3>Author(s) Disclosures</h3> None

Computerized cognitive interventions for preventing dementia in people with mild cognitive impairment: A systematic review with meta‐analyses

AbstractBackgroundPeople with mild cognitive impairment (MCI) are faced with a higher risk of developing dementia, but with a “window of opportunity” for prevention and treatment. Computerized cognitive interventions (CCIs) might constitute a beneficial non‐pharmacological treatment approach. This systematic review evaluated evidence of CCIs performed individually with a computer, tablet‐PC, game consoles, virtual reality (VR), or augmented reality (AR) on cognition in community‐dwelling people with MCI.MethodA systematic review and meta‐analyses of randomized controlled trials (RCTs) was performed. The systematic literature search was conducted in MEDLINE, CINAHL, Embase, Cochrane CENTRAL, IEEE Xplore Digital Library, ISI Web of Knowledge, Scopus and PsycINFO, and included an additional search for gray literature. The search was completed by backward citation tracking. The methodological quality of the included RCTs was independently assessed by two reviewers. Comparable studies were pooled using the random‐effects model.ResultA total of 18 randomized controlled trials (RCTs) were identified. 12 RTCs were used for conducting meta‐analyses which showed significant effects of CCIs for people with MCI in memory (SMD 1.12, CI 95% [0.08, 2.16]), working memory (SMD 0.85, CI 95% [0.32, 1.38]), attention/concentration/processing speed (SMD 0.61, CI 95% [0.21, 1.02]), executive functioning (SMD 0.96, CI 95% [0.26, 1.66]), and language (SMD 1.63, CI 95% [0.20, 3.06]), but no significant improvement in global cognition. Pooling follow‐up evaluations was not possible, but one of two studies showed continuing significant differences for the intervention group after 6 months post intervention in memory and working memory. CCIs were conducted predominantly with computers, followed by tablet‐PCs, VR, AR, and mixed reality.ConclusionThis review demonstrated beneficial effects of CCIs on domain‐specific cognition in people with MCI. Therefore, CCIs might be a valuable treatment option to maintain cognition and prevent progression to dementia. However, further research is necessary, especially on CCIs applied with emerging technologies like VR or AR. Furthermore, various outcome measurements used in the studies were challenging for the pooling of study results, which highlights the need for a predefined set of important cognitive outcomes and tools for future RCTs.

Computerized cognitive interventions for preventing dementia in people with mild cognitive impairment: A systematic review with meta-analyses.

People with mild cognitive impairment (MCI) are faced with a higher risk of developing dementia, but with a "window of opportunity" for prevention and treatment. Computerized cognitive interventions (CCIs) might constitute a beneficial non-pharmacological treatment approach. This systematic review evaluated evidence of CCIs performed individually with a computer, tablet-PC, game consoles, virtual reality (VR), or augmented reality (AR) on cognition in community-dwelling people with MCI. A systematic review and meta-analyses of randomized controlled trials (RCTs) was performed. The systematic literature search was conducted in MEDLINE, CINAHL, Embase, Cochrane CENTRAL, IEEE Xplore Digital Library, ISI Web of Knowledge, Scopus and PsycINFO, and included an additional search for gray literature. The search was completed by backward citation tracking. The methodological quality of the included RCTs was independently assessed by two reviewers. Comparable studies were pooled using the random-effects model. A total of 18 randomized controlled trials (RCTs) were identified. 12 RTCs were used for conducting meta-analyses which showed significant effects of CCIs for people with MCI in memory (SMD 1.12, CI 95 % [0.08, 2.16]), working memory (SMD 0.85, CI 95 % [0.32, 1.38]), attention/concentration/processing speed (SMD 0.61, CI 95 % [0.21, 1.02]), executive functioning (SMD 0.96, CI 95 % [0.26, 1.66]), and language (SMD 1.63, CI 95 % [0.20, 3.06]), but no significant improvement in global cognition. Pooling follow-up evaluations was not possible, but one of two studies showed continuing significant differences for the intervention group after 6 months post intervention in memory and working memory. CCIs were conducted predominantly with computers, followed by tablet-PCs, VR, AR, and mixed reality. This review demonstrated beneficial effects of CCIs on domain-specific cognition in people with MCI. Therefore, CCIs might be a valuable treatment option to maintain cognition and prevent progression to dementia. However, further research is necessary, especially on CCIs applied with emerging technologies like VR or AR. Furthermore, various outcome measurements used in the studies were challenging for the pooling of study results, which highlights the need for a predefined set of important cognitive outcomes and tools for future RCTs.

Efficacy of Olanzapine in Anxiety Dimension of Schizophrenia: A Systematic Review of Randomized Controlled Trials.

Anxiety symptoms and anxiety disorders are frequent in patients with schizophrenia and are associated with greater severity of both positive and negative symptoms, cognitive impairment, poorer functioning and quality of life. Accumulating evidence suggests that atypical antipsychotics may have a role in treating comorbid anxiety symptoms. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting randomized control trials (RCTs) that evaluated efficacy of olanzapine on anxiety symptoms in patients diagnosed with schizophrenia and included anxiety evaluation scales. We searched PubMed and Web of Science databases for articles in English language available until September 2021. We selected 7 studies (3 with primary data analysis, 4 with secondary data analysis) regarding the use of olanzapine in patients with schizophrenia. In fours studies olanzapine was superior to haloperidol in improving anxiety symptoms. Four studies compared olanzapine versus risperidone: in two of them risperidone was superior to olanzapine, although one study was limited by a relatively small sample size. In the other two there were no significant differences between olanzapine and risperidone-treated patients. One study found that olanzapine and clozapine were comparable in terms of efficacy. Although olanzapine was superior to haloperidol in treating anxiety, this symptom was a secondary outcome measure in most of the considered studies. Future RCTs comparing different antipsychotics and larger sample sizes may allow to develop more solid treatment strategies.

The Efficacy and Safety of Herbal Medicine with Pirfenidone in the Treatment of Idiopathic Pulmonary Fibrosis: A Systematic Review

Although there were randomized control trials (RCTs) that showed the considerable efficacy of herbal medicine (HM) in idiopathic pulmonary fibrosis (IPF) and systematic reviews on the value of some herbs in the treatment of IPF, there have been no systematic reviews comparing the combined use of complex HM against pirfenidone monotherapy in IPF. This review evaluated the efficacy of parallel administration of HM and pirfenidone in IPF treatment. We conducted a systematic review of RCTs that compared pirfenidone monotherapy against pirfenidone combined administration with HM in IPF. We searched the EMBASE, CENTRAL, PubMed, and CNKI databases for relevant RCTs published before July 2021. Six RCTs were eligible for inclusion. Compared with the control group, a greater recovery or a smaller reduction in forced vital capacity (FVC) and, in general, a valid improvement in the St. George’s Respiratory Questionnaire was observed in the treatment group. However, it should be noted that the risk of bias of the included RCTs was high or unclear in most categories. In IPF treatment, HM administered with pirfenidone effectively protected pulmonary function and improved the quality of life. However, given the number and quality of the included studies, the evidence was not strong enough to draw definitive conclusions. Well-designed future RCTs are warranted to evaluate the impact of HM on IPF.

Challenges and adaptations for a cluster-randomized control trial targeting parents of pediatric cancer survivors with obesity during the COVID-19 pandemic.

Although the COVID-19 pandemic has increased the importance of digital technology in clinical trial implementation, there is a dearth of literature reporting on challenges and strategies related to multi-site randomized controlled trials (RCTs) among pediatric cancer survivors during the pandemic. This paper discusses challenges faced in the implementation of the NOURISH-T+ trial so far (December 2019-March 2022) and describes adaptations made as a result of these disruptions in the areas of recruitment, data collection, and overall engagement. This reflection is based on a multisite cluster-RCT that aims to examine whether an intervention targeting parents as agents of change to promote healthy eating and physical activity in pediatric cancer survivors, NOURISH-T+ (Nourishing Our Understanding of Role modeling to Improve Support and Health for Healthy Transitions), reduces body mass and improves health behaviors compared to Brief NOURISH-T (Enhanced Usual Care/EUC). The COVID-19 pandemic has created and exacerbated challenges for our trial related to participant recruitment and engagement, technology access and literacy, and data collection and management, as well as COVID-related challenges (e.g., Zoom fatigue). Strategies used to address these challenges might prove helpful in future virtual or hybrid RCTs, including developing trust and rapport with participants, providing support through multiple routes of dissemination, and using data management applications (e.g., REDCap™) for automation and project management. Extra efforts to build families' trust and rapport, offering multiple routes of support, and automating as many tasks as possible are critical to ensuring the continuation of high-quality clinical trials during the COVID-19 pandemic.

Long-Term Management of Generalised Anxiety Disorder with Low-Dose Continuous Infusions of Flumazenil: A Case Series

Generalised anxiety disorder (GAD) is a common anxiety disorder associated with social and occupational impairment. Recently, a theory was postulated that dysfunctional gamma aminobutyric acid type A receptors (GABAA) are implicated in anxiety symptomology, which could be corrected by flumazenil, an antagonist at the benzodiazepine binding site on the GABAA receptor. Participants had a primary diagnosis of GAD and were treated initially with an eight-day continuous low-dose flumazenil infusion (total 32 mg at a rate of 4 mg/24 h). Some participants were re-treated with a further four- or eight-day infusion. Treatment response was measured as a 50% reduction in anxiety or stress scores on the Depression Anxiety Stress Scale-21 (DASS-21). Remission was measured as scores ≤3 or ≤7 on the anxiety and stress subscales of the DASS-21, respectively. Eight cases are reported. All cases met the criteria for treatment response on the anxiety and stress subscale of the DASS-21. Remission was achieved in seven participants on the anxiety subscale and in five on the stress subscale. No changes in hepatic, renal, or haematological function were likely attributed to flumazenil. Data suggest that low-dose continuous flumazenil infusion manages GAD symptoms and is safe. Although these results are promising, future randomised control trials are required to confirm these results.

(C)onsumer focused (E)ducation on p(A)racetamol (S)ide (E)ffects, i(N)adequate (O)utcomes and (W)eaning (CEASE NOW) for individuals with low back pain: results of a feasibility study

ObjectivesTo determine the feasibility of a patient-education booklet to support patients with low back pain (LBP) to reduce paracetamol intake.DesignSingle group, repeated measures feasibility study.SettingCommunity.ParticipantsAdults experiencing LBP of any kind...

Effects of sodium-glucose co-transporter-2 inhibitors on kidney, cardiovascular, and safety outcomes in patients with advanced chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.

The overall effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with advanced chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR), 15-30ml/min per 1.73 m2) remain unclear, and we thus conducted a systematic review and meta-analysis to evaluate the effects of SGLT2 inhibitors on kidney, cardiovascular (CV), and safety outcomes in patients with advanced CKD. The Medline, Embase, and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) published up to March 3, 2022, and reporting effects of SGLT2 inhibitors on kidney, CV, or safety outcomes in patients with advanced CKD. From 2675 records, six RCTs with 2167 participants were included in the quantitative analyses. In patients with advanced CKD, SGLT2 inhibitors reduced the risk of the primary kidney outcome (a composite of worsening kidney function, end-stage kidney disease (ESKD), or kidney death) by 23% (RR 0.77, 95% CI 0.61-0.98, p = 0.04, I2 = 0 for the heterogeneity) and slowed the annual decline in eGFR slope, with the difference between SGLT2 inhibitor group and placebo group being 1.24mL/min/1.73m2 per year (95% CI 0.06-2.42, p = 0.04). SGLT2 inhibitors were also associated with a decreased risk of primary CV outcome (a composite of CV death or hospitalization for heart failure) (HR 0.71, 95% CI 0.53-0.96, p = 0.03, I2 = 0 for the heterogeneity) and with similar risks of adverse events (such as acute kidney injury, fracture, amputation, and urinary tract infection). Among patients with advanced CKD, SGLT2 inhibitors reduced the risks of primary kidney and CV outcomes and attenuated the progressive decrease in eGFR compared with placebo, with no evidence of additional safety concerns. These observed benefits may support continuing the use of SGLT2 inhibitors in patients with advanced CKD before initiating maintenance dialysis or kidney transplantation. Future large-scale RCTs are needed to confirm the robustness of these results.

The Correlation Between Otitis Media With Effusion and Adenoid Hypertrophy Among Pediatric ‎Patients: A Systematic Review‎.

Otitis media with effusion (OME) affects approximately 80% of children due to the middle ear being flooded with fluids, though with no microbial infection manifestations. Multiple issues can drive recurring pediatric OME, such as environment-based issues, previous medical issues, inherited vulnerability from family, contact time at childcare institutes, passive smoking, and more than three siblings together with atopy or allergic rhinitis. If OME is not promptly addressed, this could eventually result in hearing impairment or loss, with consequent negative repercussions on the child's communicative and behavioral patterns. OME diagnosis within the clinic is possible, with hearing capacity being assessed pre- and post-therapy. Adenoid hypertrophy (AH) represents a typical causative factor for middle-ear conditions, stemming from mechanical or anatomical issues. Consequently, adenoid size is paramount when determining tympanometry types and ear fluids. This systematic review investigated PubMed, Medline, Cochrane Library, and Science Direct databases in order to retrieve knowledge related to this issue, adopting inclusion and exclusion criteria and maintaining review quality through the employment of the Assessment of Multiple Systematic Reviews (AMSTAR), the Newcastle-Ottawa tool, and the Axis scale. This systematic review analyzed a previous review article, six observation-based investigations, andthree cross-sectional investigations. Previous randomized controlled trials (RCTs) were not found within previous literature, suggesting such scarcity in this research niche and thus warranting future RCT investigations based on this compelling research niche.

Multi-Institutional Matched Comparison of Radical Cystectomy to Trimodality Therapy for Muscle Invasive Bladder Cancer (MIBC)

<h3>Purpose/Objective(s)</h3> Prior randomized controlled trials (RCT) comparing bladder preservation to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC) closed early due to lack of accrual. Given that no future RCTs are foreseen, and in the absence of level 1 data, we aimed to provide the best evidence possible on outcomes of matched cohorts comparing trimodality therapy (TMT, maximal transurethral resection of bladder tumor followed by concurrent chemoradiation) to RC in order to guide management. <h3>Materials/Methods</h3> This retrospective analysis included 703 patients with MIBC clinical stage T2-T3/4aN0M0 MIBC urothelial carcinoma of the bladder, 421 RC and 282 TMT who would have been eligible for both TMT or RC, treated at three tertiary referral academic institutions between 2005-2017. To compare homogeneous cohorts, all patients included in this analysis had solitary tumors <7 cm, no or unilateral hydronephrosis, and no extensive carcinoma in situ. Treatment propensity scores were estimated using logistic regression, and patients were matched 3:1 with replacement. Covariates included age, sex, clinical T stage, hydronephrosis, (neo)adjuvant chemotherapy, body mass index, smoking history, and ECOG status. Overall survival (OS) was estimated with adjusted Cox models; cancer-specific survival (CSS), distant failure-free survival, pelvic nodal failure-free survival and metastasis-free survival (combined distant and pelvic nodal failure) were estimated with adjusted competing risk models. Our primary endpoint of interest was metastasis-free survival. The analysis was performed as intent-to-treat. <h3>Results</h3> The 3:1 matched cohort comprised of 1,116 patients (834 RC vs 282 TMT). After matching, age (71.3 vs 71.6), cT2 clinical stage (88 vs 90%), presence of hydronephrosis (12 vs 10%), and use of (neo)adjuvant chemotherapy (60 vs 65%) was similar between RC and TMT cohorts. Salvage cystectomy was performed in 38 patients (13%) treated by TMT. At 5 years, metastasis-free (73 vs 78%, p=0.07), distant failure-free (78 vs 82%, p=0.14), and pelvic nodal failure-free (96 vs 94%, p=0.33) survival were not statistically different between RC and TMT, whereas CSS and OS favored TMT (78 vs 85%, p=0.02; 66 vs 78%, p<0.001). Outcomes for RC and TMT were not different among centers. Final pT stage in the RC patients was: pT0 14%, pT1 7%, pT2 29%, pT3/4 42% and N+ 24%. Peri RC mortality was 2.1% and median number of nodes removed was 40. NMIBC recurrence occurred in 57/282 (20.2%) TMT patients. <h3>Conclusion</h3> This large multi-institutional contemporary study provides the best evidence to date, in the absence of randomized trials, supporting TMT for select patients with MIBC. Oncologic outcomes seem to be equivalent between TMT and RC, affirming the position that TMT should be offered as an effective alternative.

Patterns of Regional Radiotherapy Following Breast Conserving Surgery in Hormone Receptor Positive Breast Cancer with Limited Nodal Disease: A Single Institutional Experience

<h3>Purpose/Objective(s)</h3> Since the publication of ACOSOG Z0011 in 2010, and the subsequent analysis of its radiation field design in 2014, there has been controversy about the extent of regional radiotherapy (RT) for patients with early-stage breast cancer found to have limited axillary nodal disease at time of breast conserving surgery (BCS). Furthermore, the MA.20 and EORTC 22922/10925 trials, both published in 2015, found that the addition of regional nodal RT to the internal mammary nodal chain (IMN) and upper axillary nodes including the supraclavicular region (SCV) demonstrated a reduction in regional and distant recurrences. Given the varying acceptable options for regional RT in this patient population, we sought to characterize the practice patterns at our institution. <h3>Materials/Methods</h3> Retrospective data from 2001-2021 were reviewed from a single provider to eliminate inter-provider variation. Included patients had estrogen receptor positive, HER2-negative breast cancer, and were found to have 1-3 positive axillary lymph nodes (LN) at time of upfront BCS. Univariate analyses were conducted to describe variations in treatment patterns. <h3>Results</h3> When divided by dates of diagnoses from 2001-2010 (n=82), 2011-2014 (n=44), and 2015-2021 (n=88) based on the publication of the landmark trials listed above, several significant trends were seen. There was a significant shift in radiation target, with a decrease in treating breast alone in favor of treating the breast + low axilla (Table 1). For patients in whom nodal irradiation was used, there was a significant increase in the inclusion of the IMN (0%, 9.1%, 25.0%; p<0.001). There was an increase in the utilization of sentinel LN biopsy resulting in a decrease in the median number of LN removed (11, 5, 3, respectively; p<0.001). This resulted in an increase in the mean ratio of positive LN to total LN removed (0.19, 0.39. 0.51, respectively; p<0.001). For patients treated from 2011-2021, those who received radiation to the SCV +/- IMN had larger tumors (mean 2.42 vs 1.75 cm, p=0.003), higher rates of ≥2 positive LN (40.8% vs 8.43%, p<0.001), and more lymphovascular invasion (60.5% vs 27.4%, p=0.002) compared to those who received radiation to the breast +/- low axilla. <h3>Conclusion</h3> Radiation target volumes have evolved over time in response to the publication of multiple randomized trials comparing different surgical approaches and radiation techniques. There is still significant heterogeneity, especially in treating patients with low-risk, node-positive breast cancer. Thus, future randomized control trials should consider enrolling patients across a broad range of radiation target volumes to align with contemporary treatment patterns.

Pain Response Rates after Conventional Radiation Therapy for Bone Metastases Assessed Using International Consensus Pain Response Endpoints: A Systematic Review and Meta-Analysis of Initial Radiation Therapy and Re-Irradiation

<h3>Purpose/Objective(s)</h3> Previous systematic reviews of conventional radiation therapy (RT) for painful bone metastases showed response rates of 72%<b>–</b>75% for initial RT and 68% for re-irradiation. However, the definition of pain response differed among studies included in these reviews. The International Consensus Pain Response Endpoints (ICPRE) was published in 2002 and revised in 2012 to unify evaluation methods for pain response internationally and has been used in many studies. We conducted a systematic review and meta-analysis to determine the pain response rates assessed by ICPRE for both initial RT and re-irradiation. <h3>Materials/Methods</h3> A literature search was conducted in PubMed and Scopus for articles published between 2002 and 2021. The inclusion criteria were as follows: (i) the study designs of randomized controlled trials (RCTs), prospective studies, or studies based on prospectively collected data; and (ii) studies in which pain response was assessed using ICPRE. Our primary outcomes of interest were overall response (OR) rates (sum of complete response rate and partial response rate) for both initial RT and re-irradiation. The following subgroup analyses were performed for OR rates of initial RT: RCT vs. non-randomized studies, with vs. without exclusion criteria for complicated bone metastases, with vs. without eligibility criteria for no change in analgesic use at enrollment, and timing of response assessment (≤1 month vs. >1 month). Random effects logistic models were used to estimate pooled response rates. <h3>Results</h3> Of the 6470 articles identified in our database search, 32 and 3 met the inclusion criteria for analysis of initial RT and re-irradiation, respectively. The OR rates of initial RT in evaluable patients (n = 4775) and intent-to-treat patients (n = 6775) were 60.4% (95% confidence interval [CI], 55.2–65.4) and 45.4% (95% CI, 38.7–52.4), respectively. The OR rates of re-irradiation in evaluable patients (n = 733) and intent-to-treat patients (n = 1085) were 70.8% (95% CI, 15.7–96.9) and 62.2% (95% CI, 5.3–98.0), respectively. Subgroup analyses of initial RT showed no significant differences in any of the comparisons, indicating similar response rates across different study designs. <h3>Conclusion</h3> We determined the pain response rates of initial RT for painful bone metastases assessed by ICPRE. The OR rate assessed by ICPRE was lower than previously reported. The present review may provide benchmarks for future RCTs and non-randomized studies. Regarding the response rate for re-irradiation, the wide range of the 95% CI warrants that the OR rate based on ICPRE requires further investigation.