Large Randomized Controlled Trials Research Articles

Management and Pharmacological Treatment of Peripheral Arterial Disease.

Background: Peripheral arterial disease (PAD) is a complex, heterogeneous condition that has become a leading health concern globally. Peripheral arterial disease often co-exists with other vascular disease states, including cerebrovascular and cardiovascular disease. Optimal therapy for managing symptoms and progression of disease employs non-pharmacological, pharmacological, and contemporary revascularisation techniques to improve clinical outcomes and quality of life. However, large well-designed randomised control trials (RCT) and corresponding evidence-based guidelines for management of PAD are lacking, with current practice standards often extrapolated from evidence in coronary artery disease.Purpose: This review article aims to discuss currently accepted best pharmacological practice for PAD.Method: Relevant articles were searched between May 2023 and January 2024 through PubMed, Cochrane Library, Google Scholar and international guidelines, focusing on pharmacological management for PAD.Results: This narrative review discusses holistic pharmacological treatments for PAD.

Efficacy and Safety of Tirzepatide in Overweight and Obese Adult Patients with Type 1 Diabetes.

Introduction and Objective: Most patients with type 1 diabetes (T1D) in the United States are overweight (OW) or obese (OB), contributing to insulin resistance and suboptimal glucose control. The primary Food and Drug Administration-approved treatment for T1D is insulin, which may adversely affect weight. Tirzepatide is approved for managing type 2 diabetes, improves glucose control, facilitates weight loss, and improves cardiovascular disease outcomes. We assessed the use of tirzepatide in OW/OB subjects with T1D. Methods: This was a retrospective single-center real-world study in 62 OW/OB adult patients with T1D who were prescribed tirzepatide (treated group) and followed for 1 year. At least 3 months of use of tirzepatide was one of the inclusion criteria. Based on the inclusion criteria, this study represents 62 patients out of 184 prescribed tirzepatide. The control group included 37 OW/OB patients with T1D (computer frequency matched by age, duration of diabetes, gender, body mass index (BMI), and glucose control) who were not using any other weight-loss medications during the same period. The mean (±standard deviation [SD]) dose of weekly tirzepatide at 3 months was 5.6 ± 1.9 mg that increased to 9.7 ± 3.3 mg at 1 year. Results: The gender, mean baseline age, duration of diabetes, and glycosylated hemoglobin (HbA1c) were similar in the two groups, whereas BMI and weight were higher in the treated group. There were significantly larger declines in BMI and weight in the treated group than in controls across all time points among those in whom data were available. HbA1c decreased in the treated group as early as 3 months and was sustained through a 1-year follow-up (-0.67% at 1 year). As expected, insulin dose decreased at 3 months and throughout the study period. There were no reported hospitalizations from severe hypoglycemia or diabetic ketoacidosis. The mean glucose, time-in-range, time-above-range, SD, and coefficient of variation (continuous glucose monitoring metrics) significantly improved in the treated group. Conclusions: In this pilot (off label) study, we conclude that tirzepatide facilitated an average 18.5% weight loss (>46 pounds) and improved glucose control in OW/OB patients with T1D at 1 year. For safe use of tirzepatide in patients with T1D, we strongly recommend a large prospective randomized control trial in OW/OB patients with T1D.

Long-Term Effect of Salt Substitution for Cardiovascular Outcomes : A Systematic Review and Meta-Analysis.

Salt substitution is a simple yet increasingly promising strategy to improve cardiovascular outcomes. To evaluate the long-term effects of salt substitution on cardiovascular outcomes. PubMed, EMBASE, Cochrane CENTRAL, and CINAHL searched from inception to 23 August 2023. Trial registries, citation analysis, and hand-search were also done. Randomized controlled trials (RCTs) comparing provision of or advice to use a salt substitute with no intervention or use of regular salt among adults for 6 months or longer in total study duration. Two authors independently screened articles, extracted data, and assessed risk of bias. Primary outcomes include mortality, major cardiovascular events (MACE), and adverse events at 6 months or greater. Secondary and post hoc outcomes include blood pressure, cause-specific mortality, and urinary excretion at 6 months or greater. Random-effects meta-analyses were done and certainty of effect estimates were assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Of the 16 included RCTs, 8 reported on primary outcomes. Most (n = 7 of 8) were done in China or Taiwan, 3 were done in residential facilities, and 7 included populations of older age (average 62 years) and/or with higher-than-average cardiovascular risk. In this population, salt substitute may reduce risk for all-cause mortality (6 RCTs; 27 710 participants; rate ratio [RR], 0.88 [95% CI, 0.82 to 0.93]; low certainty) and cardiovascular mortality (4 RCTs; 25 050 participants; RR, 0.83 [CI, 0.73 to 0.95]; low certainty). Salt substitute may result in a slight reduction in MACE (3 RCTs; 23 215 participants; RR, 0.85 [CI, 0.71 to 1.00]; very low certainty), with very low-certainty evidence of serious adverse events (6 RCTs; 27 995 participants; risk ratio, 1.04 [CI, 0.87 to 1.25]). The evidence base is dominated by a single, large RCT. Most RCTs were from China or Taiwan and involved participants with higher-than-average cardiovascular risk; therefore, generalizability to other populations is very limited. Salt substitution may reduce all-cause or cardiovascular mortality, but the evidence for reducing cardiovascular events and for not increasing serious adverse events is uncertain, particularly for a Western population. The certainty of evidence is higher among populations at higher cardiovascular risk and/or following a Chinese diet. National Health and Medical Research Council. (PROSPERO: CRD42022327566).

Improving outcomes in atherosclerotic renovascular disease: importance of clinical presentation and multi-disciplinary review.

Atherosclerotic renal artery stenosis may cause hypertension, chronic kidney disease and heart failure, but large randomized control trials to date have shown no major additional benefit of renal revascularization over optimal medical management. However, these trials did not consider outcomes specifically in relation to clinical presentations. Given that atherosclerotic renal artery stenosis is a heterogenous condition, measures of success likely differ according to the clinical presentation. Our retrospective study objectives were to determine the effects of revascularization when applied to specific clinical presentations and after careful multi-disciplinary team review. All patients presenting to our centre and its referring hospitals with radiological findings of at least one renal artery stenosis > 50% between January 2015 and January 2020 were reviewed at the renovascular multi-disciplinary team meeting with revascularization considered in accordance with international guidelines, notably for patients with anatomically significant renal artery stenosis, adequately sized kidney and presentations with any of; deteriorating kidney function, heart failure syndrome, or uncontrollable hypertension. Optimal medical management was recommended for all patients which included lipid lowering agents, anti-platelets and anti-hypertensives targeting blood pressure ≤ 130/80mmHg. The effect of revascularization was assessed according to the clinical presentation; blood pressure and number of agents in those with renovascular hypertension, delta glomerular filtration rate in those with ischaemic nephropathy and heart failure re-admissions in those with heart failure syndromes. During this 5-year period, 127 patients with stenosis ≥ 50% were considered by the multidisciplinary team,with 57 undergoing revascularization (17 primarily for severe hypertension, 25 deteriorating kidney function, 6 heart failure syndrome and 9 for very severe anatomical stenosis). Seventy-ninepercent of all revascularized patients had a positive outcome specific to their clinical presentation, with 82% of those with severe hypertension improving blood pressure control, 72% with progressive ischaemic nephropathy having attenuated GFR decline, and no further heart failure admissions in those with heart failure. Seventy-eight percent of patients revascularized for high grade stenosis alone had better blood pressure control with 55% also manifesting renal functional benefits. Multi-disciplinary team discussion successfully identified a group of patients more likely to benefit from revascularization based on 3 key factors: clinical presentation, severity of the renal artery lesion and the state of the kidney beyond the stenotic lesion. In this way, a large proportion of patients can clinically improve after revascularization if their outcomes are considered according to the nature of their clinical presentation.

Establishment and validation of a nomogram model for predicting ovulation in the PCOS women.

The mechanisms underlying ovulatory dysfunction in PCOS remain debatable. This study aimed to identify the factors affecting ovulation among PCOS patients based on a large sample-sized randomized control trial. Data were obtained from a multi-centered randomized clinical trial, the PCOSAct, which was conducted between 2011 and 2015. Univariate and multivariate analysis using binary logistic regression were used to construct a prediction model and nomogram. The accuracy of the model was assessed using receiver operating characteristic (ROC) curves and calibration curves. The predictive variables included in the training dataset model were luteinizing hormone (LH), free testosterone, body mass index (BMI), period times per year, and clomiphene treatment. The ROC curve for the model in the training dataset was 0.81 (95% CI [0.77, 0.85]), while in the validation dataset, it was 0.7801 (95% CI [0.72, 0.84]). The model showed good discrimination in both the training and validation datasets. Decision curve analysis demonstrated that the nomogram designed for ovulation had clinical utility and superior discriminative ability for predicting ovulation. The nomogram composed of LH, free testosterone, BMI, period times per year and the application of clomiphene may predict the ovulation among PCOS patients.

Value of phosphodiesterase 5 inhibitors as a combination therapy for treating erectile dysfunction: A literature review

AbstractErectile dysfunction (ED) is increasing in prevalence, with estimates that 50% of men between 40 and 70 years of age suffer from the disease. Due to a wide array of available medical interventions, significant focus has been put on combination therapies that can treat ED refractory to first‐line treatments such as phosphodiesterase 5 inhibitors (PDE5is). However, reviews evaluating monotherapy noninferiority and patient satisfaction of monotherapy versus combination therapy are lacking. A thorough PubMed search was performed to evaluate combination therapy in ED treatment. Articles published between January 2008 and June 2023 were reviewed, including randomized control trials, retrospective analyses, and cohort studies. Combination therapies included PDE5i plus another PDE5i, testosterone supplementation, α‐blockers, vacuum erectile devices, intracavernosal injections, and low‐intensity shockwave therapy. Based on this review, PDE5i monotherapy is not inferior to combination therapy and has increased satisfaction, convenience, and ease of use for patients with ED. Limitations of current literature on combination therapy include small sample size, limited data on patient satisfaction, possible biases, and limited follow‐up time. Further studies will need larger randomized control trials with follow‐up times greater than 1 year.

Conservative vs Surgical Treatment of Anterior Cruciate Ligament Rupture: A Systematic Review.

Anterior cruciate ligament (ACL) injury is very common, especially in young athletic individuals who injure themselves during sports involving pivoting actions. Management options include conservative management, which involves progressive physical therapy, educating the patient on how to prevent instability, and the use of a hinged knee brace. Surgical management involves reconstruction of the torn ligament using an autograft or an allograft and ACL repair where the torn ligament is affixed back to the tibia or femur.The choice of management depends on the severity of the injury, other injuries in associated structures, the level of fitness, and the athletic goals of the patient. Many studies exist on the management choice of ACL injury, but no clear consensus prevails. This study will examine the effectiveness of conservative versus surgical management. A literature review will be performed to identify appropriate papers which compare and evaluate the two approaches. A literature search for randomized controlled trials (RCTs) and cohort studies comparing the conservative to surgical management of ACL injury was conducted on PubMed, Scopus, and Web of Science. Patient eligibility criteria included individuals older than 15 with an isolated, recent ACL injury diagnosis via an appropriate clinical test, MRI, or arthroscopy. Studies were eligible if they were using appropriate surgical or conservative methods, as mentioned previously, and measuring results via appropriate scores, tools, and methods that will be presented below. The follow-up timeline would be from presentation time until at least two years. Five papers were found to be eligible. Overall, these papers included 462 patients. Two studies measuring overall knee symptoms, function, and sports activities using the International Knee Documentation Committee Subjective Knee Form (IKDC) score found that the operated group had a significantly higher score. The other two studies measured overall knee function and health using the Tegner & Lysholm and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores. In both papers, no significant difference was found between the two groups. Regarding Tegner's activity score, only one paper had significant findings. A significantly longer period to return to sports activities was observed in the operative group. Stability was significantly higher in all papers in the operated group. Osteoarthritis was measured using different tools in each paper. Only one paper found a significantly higher risk in the operated group. Only one paper indicated significantly more complications in the operated group regarding side effects. Overall, very few differences were observed between the two treatment groups. The most significant differences observed were the higher stability and the longer recovery period in patients undergoing surgery. Large RCTs following patients for enough time are needed to prove if surgical treatment offers significant benefits over conservative treatment.

Tamoxifen Dose De-Escalation: An Effective Strategy for Reducing Adverse Effects?

Tamoxifen, a cornerstone in the adjuvant treatment of estrogen receptor-positive breast cancer, significantly reduces breast cancer recurrence and breast cancer mortality; however, its standard adjuvant dose of 20 mg daily presents challenges due to a broad spectrum of adverse effects, contributing to high discontinuation rates. Dose reductions of tamoxifen might be an option to reduce treatment-related toxicity, but large randomized controlled trials investigating the tolerability and, more importantly, efficacy of low-dose tamoxifen in the adjuvant setting are lacking. We conducted an extensive literature search to explore evidence on the tolerability and clinical efficacy of reduced doses of tamoxifen. In this review, we discuss two important topics regarding low-dose tamoxifen: (1) the incidence of adverse effects and quality of life among women using low-dose tamoxifen; and (2) the clinical efficacy of low-dose tamoxifen examined in the preventive setting and evaluated through the measurement of several efficacy derivatives. Moreover, practical tools for tamoxifen dose reductions in the adjuvant setting are provided and further research to establish optimal dosing strategies for individual patients are discussed.

Efficacy and safety of antiplatelet therapy in COVID-19: Insights from ameta-analysis of randomized controlled trials.

COVID-19 induces a pro-coagulant state with thrombotic events. This meta-analysis explores the efficacy and safety of antiplatelet-based therapy in COVID-19 patients through randomized controlled trials (RCTs). A systematic literature search until March 10, 2023, identified 7 RCTs involving 23,415 inpatients. Of these, 11,891 received antiplatelet-based treatment, and 11,524 received placebo/other drugs. Statistical analysis was performed using Review Manager 5.4. The included trials involved patients with a mean age ranging from 54.3 to 62.0 years and a prevalence of hypertension ranging from 10.9 to 65.0% and coronary artery disease ranging from 3.2 to 32.7%. The pooled analysis showed no significant difference in overall mortality between groups (RR 1.0, 95% CI 0.99-1.01, p=0.76). However, antiplatelet therapy significantly reduced major thrombotic events (RR 0.86, 95% CI 0.75-0.99, p=0.04). Conversely, it increased major bleeding risks (RR 1.62, 95% CI 1.24-2.12, p=0.0005). There was no significant difference in the incidence of invasive mechanical ventilation and respiratory death. Antiplatelet therapy does not confer mortality benefit in COVID-19 patients but lowers major thrombotic events while increasing major bleeding risks. Ongoing large RCTs will provide more information on the therapeutic value of this therapy.

Efficacy and safety of the Valsalva maneuver in relieving venipuncture pain in children and adults: A systematic review and meta-analysis.

Venipuncture is a common invasive clinical procedure, and pain management during puncture has been of interest to healthcare professionals. The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of the Valsalva maneuver (VM) for the relief of venipuncture pain in children and adults. PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP database, and CBM were searched from inception to December 2023 for all available randomized controlled trials (RCTs) that evaluated the impact of VM on venipuncture. Two reviewers independently performed study selection, data extraction, and risk of bias assessment. Continuous variables were analyzed by mean differences (MD) or standardized mean differences (SMD), whereas dichotomous variables were analyzed by risk ratios (RR). A total of 22 studies involving 1740 participants were included. The pooled results showed that VM relieved pain intensity during venipuncture in children (SMD = -0.89, 95% CI = -1.47 to -0.30, p = 0.003) and adults (SMD = -1.11, 95% CI = -1.46 to -0.77, p < 0.00001), reduced anxiety intensity (SMD = -1.07, 95% CI = -1.68 to -0.47, p = 0.0005), and shortened puncture time (MD = -13.52, 95% CI = -21.14 to -5.90, p = 0.0005). There was no significant difference in the success rate of venous cannulation, MAP, HR, or incidence of adverse events in subjects who performed VM compared to controls. VM was an effective and safe method of pain management that reduced pain intensity during venipuncture in children and adults without significant adverse effects. The results of this meta-analysis need to be further validated by more rigorous and larger RCTs.

Effect of mindfulness-based interventions on people with prehypertension or hypertension: a systematic review and meta-analysis of randomized controlled trials

BackgroundHypertension and prehypertension have been widely recognized as the main contributors of global mortality. Evidence shows mindfulness-based interventions may reduce blood pressure and improve mental health. However, the effect of mindfulness-based interventions on blood pressure and mental health has not been fully understood.MethodsPotential studies published before May 24th 2023 were identified by searching Embase, Ovid Emcare, PsycINFO, CINAHL, Web of Science, Cochrane, PubMed, China National Knowledge Infrastructure, Wanfang database, and VIP China Science. Additionally, two grey databases were searched: Mednar, WorldWideScience.org. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias Assessment tool. The random-effects meta-analyses were conducted using Review Man 5.4 software and the key outcomes are presented as mean difference or standard mean difference and the 95% confidential interval.ResultsSearches returned 802 studies in total, of which 12 were included (N = 715). The duration of interventions was 8 weeks in 10 trials and 6 weeks in one trial. Pooled effect sizes indicated reductions in systolic blood pressure (MD = − 9.12, 95% CI [− 12.18, − 6.05], p < 0.001), diastolic blood pressure (MD = − 5.66, 95% CI [− 8.88, − 2.43], p < 0.001), anxiety (SMD = − 4.10; 95% CI [− 6.49, − 1.71], p < 0.001), depression (SMD = − 1.70, 95%CI [− 2.95, − 0.44], p < 0.001) and perceived stress (SMD = − 5.91, 95%CI [− 8.74, − 3.09], p < 0.001) at post-intervention. The findings from subgroup analyses are favorable for mindfulness-based interventions regardless of gender and baseline blood pressure with regard to BP reduction, with a more profound effect observed in participants with higher pre-intervention blood pressure.ConclusionsThe results provide evidence for the positive role of mindfulness-based interventions in hypertension management. More large randomized control trials with sufficient statistical power and long-term follow-up are needed.Trial registrationThe protocol had been registered with Prospero on October 2nd 2021 (registration NO. CRD42021282504).

Effect of prone positioning on survival in adult patients receiving venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a prospective multicenter randomized controlled study.

Current data supporting the use of prone positioning (PP) during venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with acute respiratory distress syndrome (ARDS) are limited. This prospective randomized controlled study aimed to determine whether PP implemented within 24 hours of ECMO can improve survival in these patients. From June 2021 to July 2023, 97 adult patients receiving VV-ECMO for ARDS in three centers were enrolled and 1:1 randomized into PP (n=49) and control groups (n=48). Patients in the PP group receiving prone positioning, while the control group were maintained in the supine position. The primary outcome was 30-day survival, and secondary outcomes included in-hospital survival and other clinical outcomes. All 97 patients were included for analysis. Patient characteristics did not significantly differ between the two groups. The median duration of PP was 81 hours, and the median number of PP sessions was 5 times. PP improved oxygenation and ventilator parameters. The incidence of complications during PP was low, with pressure sores being the most frequent (10.2%). The 30-day survival was significantly higher in the PP group (67.3% vs. 45.8%; P=0.033), as was in-hospital survival (61.2% vs. 39.6%; P=0.033). In the PP group, the successful ECMO weaning rate was significantly higher (77.5% vs. 50.0%; P=0.005), and the duration of ECMO support was significantly shorter {10 [8-11] vs. 10 [8-14] days; P=0.038}. However, in subgroup analysis of COVID patients the 30-day survival, in-hospital survival, successful ECMO weaning rate and the duration of ECMO support did not differ between the groups. The duration of mechanical ventilation, length of intensive care unit stay, and length of hospital stay did not significantly differ between the groups. When initiated within 24 hours of ECMO, PP can improve 30-day survival in patients with ARDS receiving VV-ECMO. In addition, it may improve the successful ECMO weaning rate and reduce the duration of ECMO support. However, considering the limitations, more strictly designed, large sample prospective randomized controlled trials are proposed. Chinese Clinical Trial Registry ChiCTR2300075326.

The relationship between use of SGLT2is and incidence of respiratory and infectious diseases and site-specific fractures: a meta-analysis based on 32 large RCTs.

We aimed to evaluate the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and incidence of various respiratory and infectious diseases and site-specific fractures. Large randomized controlled trials (RCTs) of SGLT2is enrolling more than 400 subjects were included. Outcomes of interest were various serious adverse events regarding to respiratory and infectious disorders and site-specific fractures. Meta-analysis was done using risk ratio (RR) and 95% confidence interval (CI) as effect size. Thirty-two large RCTs were included in this meta-analysis. Use of SGLT2is was significantly associated with the lower incidences of 6 kinds of noninfectious respiratory diseases {e.g., Asthma (RR 0.64, 95% CI 0.43-0.96; P = 0.0299), Chronic obstructive pulmonary disease [COPD] (RR 0.75, 95% CI 0.62-0.91; P = 0.0027), and Respiratory failure (RR 0.78, 95% CI 0.61-0.99; P = 0.0447)} and 4 kinds of infectious respiratory diseases {e.g., Bronchitis (RR 0.61, 95% CI 0.46-0.81; P = 0.0007), and Pneumonia (RR 0.85, 95% CI 0.78-0.93; P = 0.0002)}. Use of SGLT2is was not significantly associated with the incidences of 31 kinds of site-specific fractures (e.g., Hip fracture, Femoral neck fracture, and Spinal fracture; P > 0.05). Our meta-analysis confirmed the benefits of SGLT2is against 6 kinds of noninfectious respiratory diseases (e.g., Asthma, COPD, and Respiratory failure) and 4 kinds of infectious respiratory diseases (e.g., Bronchitis, and Pneumonia). These findings suggest a likelihood that SGLT2is might be used to prevent or treat these respiratory diseases. Moreover, our meta-analysis for the first time revealed no association between use of SGLT2is and incidence of various site-specific fractures.

P651 A randomised controlled trial of IBD-BOOST, a digital cognitive behavioural self-management programme for fatigue, and/or pain, and/or faecal incontinence in inflammatory bowel disease

Abstract Background Many people with IBD experience fatigue, pain and faecal incontinence (FI), impacting quality of life (QoL). We developed an interactive digital online self-management intervention (IBD-BOOST) based on a theoretically informed logic model and cognitive behavioural techniques, to treat these symptoms. We aimed to assess if IBD-BOOST, alongside health care professional (HCP) support and care as usual (CAU), provides greater relief from symptoms and improvement of QoL compared with CAU alone. Methods We conducted a pragmatic multi-centre two-arm parallel group randomised controlled trial (RCT) recruiting patients from clinics and national registries who rated the impact of fatigue and/or pain and/or FI as ≥5/10. Those in the IBD-BOOST arm received 6 months access to the 12-session IBD-BOOST programme, a 30-minute telephone support call with a trained HCP after session 1 and weekly in-site email messages from the HCP for 3 months. The UK Inflammatory Bowel Disease Questionnaire (UK-IBDQ) and global rating of symptom relief (GRSR) at 6 months were dual primary outcomes (alpha=0.025 was considered statistically significant as there were two primary outcomes). Other secondary outcomes, including individual symptoms, were measured at 6 and 12 months. Complier-averaged causal effects (CACE), sensitivity and pre-specified subgroup analyses were conducted. Results 780 participants were randomised (Figure 1), 432 with Crohn’s disease, 348 with ulcerative colitis or other IBD; 520 (66.7%) were female, mean age 49 years. At 6 months, both UK-IBDQ and GRSR were similar between the BOOST and CAU arms, p=0.19 for IBDQ and p=0.39 for GRSR (Table 1). Adverse events were similar between groups. FI score and EQ5D utility score (secondary outcomes) were significantly in favour of IBD-BOOST at 6 months, but pain and fatigue were no different. 57% of the intervention group completed a pre-defined minimum “dose” of 4 sessions (i.e. compliers). The CACE analysis suggested that compliers were more likely to report better QoL (p=0.03). Subgroup analysis of those meeting criteria for irritable bowel syndrome (IBS), showed that IBD-BOOST was more effective in improving IBDQ and GRSR at 6 months when compared with CAU for the IBD-IBS group (pinteraction=0.015 and 0.046, respectively). Conclusion This large RCT found that IBD-BOOST did not improve IBDQ and GRSR in patients with IBD and fatigue and/or pain and/or FI relative to CAU. Participants reported less FI at 6 and 12 months. Those who complied with the intervention showed a more pronounced IBDQ treatment effect. Those with IBD-IBS at baseline improved more than those without, suggesting a possible for further effectiveness research on IBD-BOOST. Trial registration: ISRCTN71618461

Paraprofessional perceptions about and use of behavior strategies in elementary schools

AbstractParaprofessionals are often tasked with implementing behavior management strategies to support the complex needs of students with disruptive behavior disorders. This study examined reported use and effectiveness of common classroom behavior strategies from 86 paraprofessionals working in 36 elementary schools using a mixed method design. Data were from a larger randomized control trial that examined the effects of behavior support coaching on paraprofessional practices and student outcomes. Qualitative analysis highlighted themes related to behavior strategies use, including 94 “other” strategies. Paraprofessionals across conditions reported use of a range of behavior management strategies and were more likely to use consequence‐based than antecedent‐based strategies (χ2 = 381; p &lt; .001; df = 1). Coached paraprofessionals reported greater use of reminding or reinforcing classroom rules and praising for appropriate behavior than controls. No group differences in overall strategy use (χ2 = 1.20; p = .273; df = 1) or overall perceived effectiveness (t = −1.45; p = .149; df = 755) were found. Implications of findings for practice and research are presented.

Frail older people with decreased cognition can perceive reduced self-determination in self-care and social relationships

BackgroundSelf-determination in old age is essential for people’s experiences of good subjective health and quality of life. The knowledge concerning how frail older people with decreased cognition perceive their ability to be self-determined in the different dimension in daily life is, however, limited. The aim of this study was therefore to explore the relationship of self-determination and cognition in frail older people.MethodsThis study was a cross-sectional secondary data analysis using baseline data with 119 frail people 75 ≥ from a larger randomized control trial. Self-determination was measured with the statements from the Impact on Participation and Autonomy-Older persons (IPA-O). Cognition was measured using the Mini Mental State Examination (MMSE), where decreased cognition was broadly defined as a score below 25 points. Fisher’s exact test was used to test differences in proportions of perceiving self-determination in relation to cognition. The Relative Risk (RR) with a 95% Confidence Interval (CI) was used to explore the risk of perceiving reduced self-determination in relation to cognitive functioning.ResultsNearly the entire study population, regardless of cognitive functioning, perceived self-determination in Financial situation. For people with decreased cognition, the relative risk for perceiving reduced self-determination was statistically significant higher in activities related to Self-care and in Social relationships when comparing with the participants with intact cognition.ConclusionPerceiving self-determination when being old, frail and having decreased cognition is possible but is dependent upon which activities that are involved. Organizing healthcare needs according to the older people’s wants and wishes is crucial regardless of people having a cognitive decline or not when the effort is to enable the people to be as self-determined as they want. The frail older people with decreased cognition should be treated as being experts in their own lives, and healthcare professionals should navigate the older people to get to their desired direction.Trial registrationClinicalTrials.gov, NCT02773914. Retrospectively registered 16 May 2016.

Pilot randomized controlled trial of EMBOLDEN: a novel co-designed community-based intervention to enhance mobility in older adults.

Introduction: Physical mobility and social participation are essential for maintaining independence and improving quality of life with aging. These are also interrelated, with barriers to mobility leading to social isolation, as well as poor physical and mental health. Most mobility-enhancing interventions in older adults have been designed by researchers without public input and delivered in controlled settings. This traditional approach to intervention design and testing may not meet the needs of older adults or prove effective in real-world implementation. To have sustained real-world impact, a model aimed at improving mobility that is person-centred, supports social network engagement, and leverages existing community health and social services is more likely to realize impacts. The EMBOLDEN intervention is a novel evidence-informed and contextually relevant community program. A Strategic Guiding Council comprised of older adults and health and social service providers co-designed the 3-month, multi-component group-based program to enhance mobility in older adults living in neighbourhoods experiencing health inequities. In this analysis, we present the implementation results of our pilot randomized controlled trial (RCT).&#x0D; Aims &amp; Methods: The pilot trial aimed to explore the feasibility and implementation of a multi-component intervention to improve mobility in older adults in preparation for a large effectiveness-implementation pragmatic RCT (EMBOLDEN, NCT05008159). Core intervention components include physical activity, healthy eating, socialization, and system navigation. Community-dwelling older adults (≥55 years) living in one neighbourhood in Hamilton, Canada, were randomized (2:1) to either: a weekly 90-minute virtual group program for 9 weeks (intervention) or continued normal routine (control). The intervention team integrated providers from recreation, primary care, and public health. A Community Advisory Board, including older adults and local providers, informed intervention modifications and implementation. Data were collected through participant quantitative surveys, study documentation, and qualitative interviews with participants and interventionists. Survey data were analyzed descriptively; survey open-text data, intervention team documentation, and transcripts were analyzed using content analysis. Process outcomes included program acceptability, intervention fidelity, implementation barriers and facilitators, and intervention feasibility/acceptability to participants and interventionists. &#x0D; &#x0D; Results: 11 participants were enrolled; 10 were randomized (6 INT; 4 CON). Participant age ranged from 57-76 years. Most participants identified as female (73%), had a total household income of &lt;$50,000 (73%) and lived alone (55%). Five participants received the allocated intervention. Quantitative and qualitative data collection are complete; analyses are underway. Intervention participants expressed perceived changes to their behaviours related to program outcomes: mobility and health; as well as increased awareness of community supports. Intervention group participants expressed positive experiences with the intervention and perceived impacts on their health and community connections. However, participants expressed a preference for in-person delivery. Interventionists gained experience delivering this multi-component intervention as a team. The COVID-19 pandemic impacted intervention duration (9 vs. 12 weeks), mode of delivery (virtual vs. in-person), and recruitment. Adaptations for the RCT include in-person delivery, longer duration, and new recruitment approaches.&#x0D; Conclusions: This pilot trial demonstrated that implementing the EMBOLDEN intervention was feasible and acceptable to participants and interventionists. The team gained important insight into modifications necessary for the larger, pragmatic RCT.

REtinal Detachment Outcomes Study (REDOS): study protocol for a factorial, randomized controlled trial

BackgroundFew large randomized controlled trials provide strong evidence to guide surgical repair of primary rhegmatogenous retinal detachment (RRD) repair. The purpose of this factorial, single-blind, randomized controlled trial is to analyze and compare the surgical outcomes, functional visual outcomes, complications, and quality of life associated with RRD repair using (A) pars plana vitrectomy only (PPV) or PPV with scleral buckle (PPV-SB) and (B) sulfur hexafluoride gas (SF6) or perfluoropropane gas (C3F8) tamponade.MethodsEligible patients with moderately complex RRD will be randomized 1:1 to PPV or PPV-SB and 1:1 to SF6 or C3F8 gas tamponade. Approximately 560 patients will be recruited to be able to detect a difference of around 10% in SSAS rate between the groups. Patients will be followed using multimodal imaging and quality of life questionnaires after the surgical repair until 1 year postoperative. The primary outcome will be a single-surgery anatomic success (SSAS), defined as the absence of reoperation for recurrent RRD in the operating room. Secondary outcomes will be pinhole visual acuity (PHVA) at 8–10 weeks and 6 months, final best-corrected visual acuity (BCVA), final retina status (i.e., attached or detached), time to onset of RRD recurrence, severity and number of complications, and questionnaire results.DiscussionThis will be the first 2 × 2 factorial RCT examining repair techniques in primary RRD. It will also be the first RCT to compare gas tamponade between the two most common agents. Notably, it will be adequately powered to detect a clinically significant effect size. The use of multimodal imaging will also be a novel aspect of this study, allowing us to compare head-to-head the impact of adding an SB to the retina’s recovery after RRD repair and of differing gas tamponades. Until now, the treatment of RRD has been largely guided by pragmatic retrospective cohort studies. There is a lack of strong evidence guiding therapeutic decisions and this trial will address (1) whether supplemental SB is justified and (2) whether longer duration gas tamponade with C3F8 is necessary.Trial registrationClinicalTrials.gov NCT05863312. Registered on 18 May 2023.

Adjunctive Systemic Corticosteroids for Pulmonary Exacerbations of Cystic Fibrosis.

Rationale: Pulmonary exacerbations (PEx) remain the most common cause of morbidity, recurrent hospitalization, and diminished survival in people with cystic fibrosis (PWCF) and are characterized by excess inflammation. Corticosteroids are potent, widely available antiinflammatory drugs. However, corticosteroid efficacy data from randomized controlled trials in PWCF are limited. Objectives: To determine whether adjunctive systemic corticosteroid therapy is associated with improved outcomes in acute CF PEx. Methods: We performed a secondary analysis of Standardized Treatment of Pulmonary Exacerbations 2 (STOP2), a large multicenter randomized controlled trial of antimicrobial treatment durations for adult PWCF presenting with PEx, that included the use of corticosteroids as a stratification criterion in its randomization protocol. Corticosteroid treatment effects were determined after propensity score matching for covariates including age, sex, baseline forced expiratory volume in 1 second (FEV1), genotype, and randomization arm. The primary outcome measure was the change in percentage predicted FEV1 (ppFEV1). Symptoms, time to next PEx, and the incidence of adverse events (AEs) and serious adverse events (SAEs) were assessed as secondary endpoints. Phenotypic factors associated with the clinical decision to prescribe steroids were also investigated. Results: Corticosteroids were prescribed for 168 of 982 PEx events in STOP2 (17%). Steroid prescription was associated with decreased baseline ppFEV1, increased age, and female sex. Cotreatment with corticosteroids was independent of treatment arm allocation and did not result in greater mean ppFEV1 response, longer median time to next PEx, or more substantial symptomatic improvement compared with propensity-matched PWCF receiving antibiotics alone. AEs were not increased in corticosteroid-treated PWCF. The total number of SAEs-but not the number of corticosteroid-related or PEx-related SAEs-was higher among patients receiving corticosteroids. Conclusions: Empiric, physician-directed treatment with systemic corticosteroids, although common, is not associated with improved clinical outcomes in PWCF receiving antibiotics for PEx. Clinical trial registered with www.clinicaltrials.gov (NCT02781610).

Effects of Peripherally inserted Central Catheter (PICC) materials and designs on reduction of PICC-related complications: A systematic review and meta-analysis.

Studies showed that integrating coating or valve into Peripherally Inserted Central(PICC) can prevent related complications. However, data regarding efficiency were controversial. Therefore, a systematic review was needed to analyse the effect of PICC materials and designs on reduction of PICC-related complications. We searched PubMed, Cochrane library, EMbase, grey literature and referent literature from inception to 5 August 2022. Randomized controlled trials (RCTs) and case-control study were included. Two authors extracted data independently, using a predesigned Excel form, and assessed the quality of included RCTs according to the Cochrane Handbook for Systematic Reviews (V5.1.0), case-control study was assessed by the Newcastle-Ottawa Scale. Data were analysed using Review Manager (v5.3.0). A total of 10 RCTs and one case-control study were included. Meta-analysis results showed that PICC designs reduce the incidence of obstruction, and at the critical value of PICC-associated bloodstream infection, but may have no effects on other complications. Based on the literature reviewed, we can only say PICC new materials did not reflect significant reduction on complications, what's more, the result needs more multicentre, large RCTs to support. We suggested clinicians combine descriptive research and cost-effect analysis to select appropriate PICC materials and designs for patients.