Adjunctive Benefit Research Articles

The Influence of Vitamin D Levels and Supplementation on the Treatment of Patients Affected by MRONJ

Background: Advancements in pharmacology have led to the introduction of novel antiresorptive and antiangiogenic drugs, which are associated with the side effect of medication-related osteonecrosis of the jaw (MRONJ). The aim of this study was to evaluate the impact of different blood levels of vitamin D on the course of treatment, as well as the role of vitamin D supplementation during the treatment of primary diseases involving bisphosphonates or denosumab. Methods: The clinical trial involved 64 patients diagnosed with medication-related osteonecrosis of the jaw (MRONJ) treated at the Department of Oral Surgery. Participants underwent baseline panoramic radiographs and Cone Beam Computed Tomography (CBCT) scans, with MRONJ severity categorized according to the AAOMS classification. This study included two groups: 37 patients (n = 37) in the experimental group received high-dose vitamin D supplementation (10,000 IU/day for 4 weeks, followed by a maintenance dose of 5000 IU/day), while 27 patients (n = 27) in the control group received no supplementation. Vitamin D levels were measured at baseline, 3 months, and 6 months, and the relationship between vitamin D supplementation and clinical outcomes, including MRONJ risk and healing, was evaluated. All participants received an antibiotic regimen pre- and post-surgery. Pain intensity was assessed at multiple time points using the Visual Analog Scale (VAS). Results: This study showed significant increases in serum vitamin D levels in the experimental group at 3 and 6 months (p < 0.05). In the prophylactic context, Vitamin D supplementation prior to or during tooth extraction reduced the risk of developing severe MJRON (OR = 68.57; p < 0.001). In the therapeutic context among patients with established MJRON, vitamin D supplementation did not significantly predict postoperative complications (p = 0.079) or complete healing (OR = 2.34; p = 0.051). However, overall healing rates were somewhat higher in the supplemented group, though they did not reach statistical significance. Antibiotic protection uses also reduced the need for further treatment (OR = 6.20; p < 0.001). Conclusions: Prophylactic high-dose vitamin D supplementation may help prevent severe MRONJ in at-risk patients undergoing tooth extraction. Once MRONJ is established, however, vitamin D alone may not significantly alter immediate postoperative outcomes, although further research is needed to clarify its potential adjunctive benefits.

Intra-arterial tenecteplase following endovascular therapy in patients with acute posterior circulation arterial occlusion: study protocol and rationale

BackgroundRecently, a randomized controlled trial showed a beneficial effect of intra-arterial thrombolysis following successful endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion in the...

Statistical analysis plan for the LAST ACT clinical trial; a Leukotriene A4 hydrolase Stratified non-inferiority Trial of Adjunctive Corticosteroids for HIV-negative adults with Tuberculous meningitis

Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Corticosteroids are currently recommended as an adjunctive therapy in HIV-negative adults with TBM. However, benefit from corticosteroids in TBM may depend upon host leukotriene A4 hydrolase (LTA4H) genotype and the corresponding inflammatory phenotypes. This article describes the planned analyses for the primary publication of the results of the LAST ACT clinical trial (NCT03100786): ‘Leukotriene A4 hydrolase Stratified Trial of Adjunctive Corticosteroids for HIV-negative adults with Tuberculous meningitis’. The primary hypothesis addressed by the trial is that LTA4H genotype, in particular CC or CT genotype, determines whether adjunctive dexamethasone benefits or harms adults with TBM. The trial was an LTA4H genotype stratified, parallel group, randomised, double blind, placebo-controlled multi-centre Phase III trial of dexamethasone given for 6–8 weeks in addition to standard anti-tuberculosis drugs. LTA4H genotype (CC, CT, TT) was determined in all participants prior to randomisation; only those with CC or CT genotype were randomised to dexamethasone or placebo. All TT genotype participants received dexamethasone because prior data indicated survival was increased by dexamethasone in this genotype. The primary endpoint was all-cause death or new neurological event over the first 12 months after randomisation. We took a hybrid trial-design approach which aims to prove non-inferiority of placebo first but also allows claiming superiority of placebo in case dexamethasone causes substantial harm. This statistical analysis plan expands upon and updates the analysis plan outlined in the published study protocol.

Recovery Horizons: Nature-Based Activities as Adjunctive Treatments for Co-Occurring Post-Traumatic Stress Disorder and Substance Use Disorders.

Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) frequently co-occur, and individuals with co-occurring PTSD and SUD often experience more complex treatment challenges and poorer outcomes compared to those with either condition alone. Integrative treatment approaches that simultaneously address both PTSD and SUD are considered the most effective and include both pharmacological and non-pharmacological strategies. In recent years, complementary interventions have garnered increased attention due to their broad appeal and potential therapeutic benefits in enhancing existing treatments for PTSD and SUD. This review explores the existing literature on the use of nature-based activities, such as hiking, camping, sailing, and surfing in treating individuals with co-occurring PTSD and SUD. Nature-based activities offer promising adjunctive benefits, including the reduction of PTSD symptoms and craving levels. While evidence supports the therapeutic value of nature-based activities, current research remains limited. Further research is needed to better understand their therapeutic role and to refine their implementation in clinical practice.

Physician-dentist dual referral model concept for coordinated bone anabolic therapy

BackgroundBone anabolic drugs used for the pharmacologic treatment of osteoporosis have the potential to enhance alveolar bone regeneration to improve implant success. There are no US Food and Drug Administration–approved drugs indicated to improve oral bone density around teeth or implants. MethodsThe authors summarized expert opinions on a novel coordinated treatment approach leveraging the effects of systemic bone anabolic drugs to enhance dental implant therapy in patients with osteoporosis and a dual referral model for physicians and dentists to address the clinical needs of patients with osteoporosis from a comprehensive perspective of oral-systemic health. Interviews of key opinion leaders were conducted with a bone health specialist group consisting of specialists in orthopedic surgery, internal medicine, geriatrics, endocrinology, and clinical densitometry and a surgical dental specialist group consisting of periodontists and oral surgeons. ResultsOverall, both groups shared positive feedback on the idea of strategically timing administration of anabolic osteoporosis drugs with dental treatment. Both groups expressed interest in the dual referral model. ConclusionsThe feedback of key opinion leaders supported the coordinated bone anabolic therapy concept and identified a need for improved interdisciplinary collaboration, education, and communication to realize the synergies of physician-dentist clinical cooperation. Practical ImplicationsStrategic timing of osteoporosis therapy could improve skeletal bone health and reduce fracture risk while offering adjunctive dental benefits.

The Role of Dietary Patterns and Nutritional Supplements in the Management of Mental Disorders in Children and Adolescents: An Umbrella Review of Meta-Analyses: Le rôle des habitudes alimentaires et des suppléments nutritionnels dans la prise en charge des troubles mentaux chez les enfants et les adolescents : une méta-revue de méta-analyses.

In recent years, the relationship between nutrition and mental health has gained considerable interest. We identified, synthesized, and appraised all meta--analyses of randomized controlled trials (RCTs) and observational studies reporting on the efficacy of dietary patterns and nutrient supplements in the prevention and treatment of mental disorders in children and adolescents. Systematic research in MEDLINE, PsycINFO, Scopus, and Cochrane Database of Systematic Reviews was completed on 8 January 2024. Our research found 24 meta-analyses: 14 on RCTs, 8 on observational studies, and 2 combining both. Emerging evidence suggests that omega-3, in particular eicosapentaenoic acid, and Vitamin D may have adjunctive benefits in the treatment of attention deficit hyperactivity disorder (ADHD), while no evidence was found for autism spectrum disorder (ASD). Observational data also indicated that prenatal folic acid supplementation (>400 μg daily) was associated with a reduced risk of ASD in offspring. In terms of dietary habits, several meta-analyses of observational data revealed that healthy dietary patterns (rich in fruits, vegetables, and fibre, low in saturated fats) during the prenatal period, childhood, and adolescence were linked to a significantly reduced risk of internalizing disorders and externalizing disorders. Conversely, unhealthy dietary habits (high in sugars, saturated animal fats, and industrial foods, low in fruits, vegetables, and fibre) are associated with an elevated risk of these mental health issues. However, the number of available studies on dietary interventions for the treatment of depression, ASD, and ADHD was limited, and the results obtained were either nonsignificant or contradictory. Our findings emphasize the need to establish clear causal relationships between dietary habits and the risk of mental illness in children and adolescents. Moreover, further investigation of the benefits observed with some nutrient supplements (such as omega-3 and vitamin D for ADHD) through larger-scale RCTs is imperative to establish more robust conclusions.

Effect of music therapy on pain and anxiety during third molar surgery

Music therapy has been used with promising results to reduce pain and anxiety in surgical specialties. It is suggested to reduce anxiety and pain perception during dental surgeries and thereby improving clinical outcomes. Aim: The aim of this study is to determine whether listening to music during trans-alveolar mandibular third molar extraction reduces pain perception and anxiety. Methods: One hundred and forty-six adult participants were randomized into music and non-music groups, with each group comprising seventy-three participants. Each participant had trans-alveolar third molar extraction with or without music intervention depending on the group randomly assigned. Pain scores of participants were measured at one minute after consent, during and after administration of local anaesthetic, during osteotomy, after tooth delivery, and one minute after flap closure. Postoperative pain scores were recorded at one-hour, 3-hour, 6-hour, 24-hour and 48-hour after the last stitch. Pre- and post-operative anxiety scores were also recorded. Descriptive statistics was used to describe sociodemographic data. Student t-test was used to compare the mean of quantitative variables between the groups while chi-square test was used to compare proportions and to investigate association between categorical variables. The statistical significance was defined at p<0.05. Results: The study showed similar sociodemographic characteristics, baseline clinical features and duration of surgery between groups. Pain score peaked during local anaesthetic administration (p = 0.254) and at 3 hours after surgery (p = 0.170) but no statistically significant difference was observed in the mean pain score. The mean anxiety scores also revealed no statistically significant differences. Conclusion: Music was found to add no significant anxiolytic and adjunctive analgesic benefit to participants who underwent third molar surgeries in this study.

IL-37 evaluation in chronic periodontitis after periodontal treatment with and without low level laser therapy.

Periodontal disease poses a significant global health challenge. Traditional treatments focus on reducing inflammation and bacterial load, yet novel approaches are continually being investigated. Recent research suggests that IL-37, a potent anti-inflammatory cytokine, may play a crucial role in modulating the inflammatory processes associated with periodontal disease. In conjunction with IL-37, low-level laser therapy (LLLT) has gained attention for its potential in promoting tissue repair, reducing inflammation, and enhancing cellular processes. This study aims to investigate the effects of LLLT on IL-37 in periodontal disease management. Thirty patients were enrolled: the G1 group patients were treated with only scaling and root planning-SRP, the G2 group was treated with SRP and LLLT. Before treatment (T0) all periodontal probing pocket depth and bleeding on probing were obtained. Before (T0) and 10 (T1), 30 (T2) and 60 (T3) days after treatment, was achieved plaque sample and specimens of gingival crevicular fluid. Diode laser wavelength range was used between 600-1000 nm and 0.04-60 J/cm2 energy density for 3-s spotlights. In all patients PPD, BOP and IL-37 have shown healing improved parameters. Although LLLT is widely recommended for its biostimulatory and anti-inflammatory roles, it only showed additional short-term merits in reducing the pocket depth after conventional SRP. Its long-term adjunctive benefits remain unclear. Future RCTs with better study designs, adequate sample power and longer durations of follow-up are required to assess the effectiveness of LLLT as an adjunctive treatment strategy in patients with periodontal disease.

Vitamin D deficiency associates inversely with COVID-19 risks; might avoidance of vitamin D inadequacy reduce those risks?

The risks of COVID-19, whether of becoming infected, needing intensive care or dying, consistently relate inversely to vitamin D status [serum 25(OH)D concentration], but low 25(OH)D is not just due to COVID-19 since they are seen in relation to pre-pandemic 25(OH)D values, both in individual cohorts and across many populations. Furthermore, many recognised risk factors for increased COVID-19 severity themselves reduce vitamin D status [e.g., obesity, dark skin, indoor lifestyles, low socio-economic status and increasing age], which complicates data analyses. Vitamin D has many mechanistic effects likely to provide adjunctive benefits protecting against COVID-19 severity. For example, vitamin D reduces the risks of microbial infection by promoting innate immunity and reduces tissue damage in severe infections by modulating the severity of adaptive immune responses. The protective mechanistic effects of correcting vitamin D inadequacy discussed support the view that increasing vitamin D status should reduce COVID-19 risks. However, many trials of cholecalciferol treatment have failed to do so, probably because it takes many weeks to raise serum 25(OH)D levels adequately whilst the increasing clinical use of the 25(OH)D metabolite [calcifediol] in COVID-19 treatment, which raises serum 25(OH)D concentrations rapidly, has led to reports of clinical benefits in COVID-19 illness.

Adjunctive benefits of low-frequency transcutaneous electrical nerve stimulation for obesity frequent chronic conditions: a systematic review.

Obesity is widely recognized for its role in predisposing individuals to a spectrum of chronic health conditions. Emerging preliminary evidence points to the potential benefits of low-frequency transcutaneous electrical nerve stimulation (Lo-TENS) in enhancing various health outcomes among those with obesity and associated disorders. This systematic review was designed to assess the effectiveness of Lo-TENS for managing obesity and its related chronic diseases. For this systematic review, we included randomized controlled trials that evaluated the impact of Lo-TENS on individuals with obesity and its associated chronic diseases. Eight trials encompassing 671 participants and spanning three unique populations: essential hypertension (EH), type 2 diabetes mellitus (T2DM), and obesity were deemed eligible for inclusion in this review. Compared to baseline measurements, Lo-TENS demonstrated a tendency to positively affect blood pressure in individuals with EH and metabolic parameters in those with T2DM. Nonetheless, the efficacy of Lo-TENS in treating obesity is not yet clear when contrasted with a no-intervention control group. When compared with other intervention modalities, three of the trials reported less favorable results. Although Lo-TENS did not consistently surpass other treatments or yield substantial improvements, it generally provided greater benefits than the majority of placebo controls. This suggests that Lo-TENS could potentially serve as a beneficial adjunctive therapy in the management of obesity and its associated conditions. However, given the limited number of trials assessed, the elevated risk of bias within these studies, and the scarce evidence currently available, it is too early to reach definitive conclusions. Caution should be exercised when interpreting the current findings. There is an imperative for further high-quality research to thoroughly investigate and substantiate the efficacy of Lo-TENS in relation to obesity and its related disorders.

Do autologous platelet concentrates (APCs) have a role in intra-oral bone regeneration? A critical review of clinical guidelines on decision-making process.

In the past decades, personalized regenerative medicine has gained increased attention. Autologous platelet concentrates (APCs) such as PRP, PRGF, and L-PRF, all serving as a source of a large variety of cells and growth factors that participate in hard and soft tissue healing and regeneration, could play a significant role in regenerative periodontal procedures. This narrative review evaluated the relative impact of APCs in alveolar ridge preservation, sinus floor augmentation, and the regeneration of bony craters around teeth, both as a single substitute or in combination with a xenograft. L-PRF has a significant beneficial effect on alveolar ridge preservation (<alveolar bone resorption, >bone quality). The data for PRGF are less convincing, and PRP is controversial. L-PRF can successfully be used as a single substitute during transcrestal (≥3.5 mm bone gain) as well as 1-stage lateral window sinus floor elevation (>5 mm bone gain). For PRGF and especially PRP the data are very scarce. In the treatment of bony craters around teeth, during open flap debridement, L-PRF as a single substitute showed significant adjunctive benefits (e.g., >PPD reduction, >CAL gain, >crater depth reduction). The data for PRP and PRGF were non-conclusive. Adding PRP or L-PRF to a xenograft during OFD resulted in additional improvements (>PPD reduction, >CAL gain, >bone fill), for PRGF no data were found. Autologous platelet concentrates demonstrated to enhance bone and soft tissue healing in periodontal regenerative procedures. The data for L-PRF were most convincing. L-PRF also has the advantage of a greater simplicity of production, and its 100% autologous character.

Adjunctive benefit of probiotic supplementation along with nonsurgical therapy for peri-implant diseases - A systematic review and meta-analysis.

Adjunctive therapy of probiotics may improve the efficacy of nonsurgical therapy of peri-implant diseases for up to 3 months. However, moderate certainty was observed for a reduction in bleeding on probing after 1-month re-evaluation alone.

Substrate Imaging Before Catheter Ablation of Ventricular Tachycardia: Risk Prediction for Acute Hemodynamic Decompensation

BackgroundThe PAINESD (Pulmonary disease, Age, Ischemic cardiomyopathy, NYHA functional class, Ejection fraction, Storm, Diabetes mellitus) risk score has been validated as a predictor of periprocedural acute hemodynamic decompensation (AHD) in patients undergoing ventricular tachycardia (VT) ablation. Whether the addition of total scar volume (TSV) determined by preprocedure computed tomography imaging provides additional risk stratification has not been previously investigated. ObjectivesThe purpose of this study was to evaluate the impact of TSV on the risk of AHD and its adjunctive benefit to the PAINESD score newly modified as Pulmonary disease, Age, Ischemic cardiomyopathy, NYHA class, Ejection fraction, Storm, Scar volume, Diabetes mellitus (PAINES2D) based on the addition of scar volumes. MethodsThis was a retrospective analysis of all index VT ablations at a quaternary care center from 2017 to 2022. Associations between TSV and AHD were evaluated among patients with structural heart disease. ResultsAmong 61 patients with TSV data, 13 (21%) had periprocedural AHD. TSV and PAINESD were independently associated with AHD risk. Both TSV and PAINESD were associated with AHD (P = 0.016 vs P = 0.053, respectively). The highest TSV tertile (≥37.30 mL) showed significant association with AHD (P = 0.018; OR: 4.80) compared to the other tertiles. The PAINESD and PAINES2D scores had significant impact on AHD (P = 0.046 and P = 0.010, respectively). The PAINES2D score had a greater impact on AHD compared to PAINESD (area under the curve: 0.73; P = 0.011; 95% CI: 0.56-0.91 and area under the curve: 0.67; P = 0.058; 95% CI: 0.49-0.85, respectively). ConclusionsAddition of TSV to a modified PAINESD score, PAINES2D, enhances risk prediction of AHD. Further prospective study is needed to assess benefit in various cardiomyopathy populations undergoing VT ablation.

Orchestral role of lipid metabolic reprogramming in T-cell malignancy.

The immune function of normal T cells partially depends on the maneuvering of lipid metabolism through various stages and subsets. Interestingly, T-cell malignancies also reprogram their lipid metabolism to fulfill bioenergetic demand for rapid division. The rewiring of lipid metabolism in T-cell malignancies not only provides survival benefits but also contributes to their stemness, invasion, metastasis, and angiogenesis. Owing to distinctive lipid metabolic programming in T-cell cancer, quantitative, qualitative, and spatial enrichment of specific lipid molecules occur. The formation of lipid rafts rich in cholesterol confers physical strength and sustains survival signals. The accumulation of lipids through de novo synthesis and uptake of free lipids contribute to the bioenergetic reserve required for robust demand during migration and metastasis. Lipid storage in cells leads to the formation of specialized structures known as lipid droplets. The inimitable changes in fatty acid synthesis (FAS) and fatty acid oxidation (FAO) are in dynamic balance in T-cell malignancies. FAO fuels the molecular pumps causing chemoresistance, while FAS offers structural and signaling lipids for rapid division. Lipid metabolism in T-cell cancer provides molecules having immunosuppressive abilities. Moreover, the distinctive composition of membrane lipids has implications for immune evasion by malignant cells of T-cell origin. Lipid droplets and lipid rafts are contributors to maintaining hallmarks of cancer in malignancies of T cells. In preclinical settings, molecular targeting of lipid metabolism in T-cell cancer potentiates the antitumor immunity and chemotherapeutic response. Thus, the direct and adjunct benefit of lipid metabolic targeting is expected to improve the clinical management of T-cell malignancies.

Adjunctive use of a nanocolloidal silver-based local antiseptic solution in the nonsurgical treatment of periodontitis: A split-mouth clinical study

Objectives. The aim of the present study was to evaluate the potential additional clinical benefit of a commercial nano colloidal silver-based local antiseptic used as irrigation solution after subgingival mechanical instrumentation. Material and methods. Periodontitis patients were treated following the current guidelines. Two randomly assigned hemiarches of each patient received subgingival mechanical instrumentation plus irrigations with the commercial product (experimental group); the other two hemiarches received mechanical instrumentation plus saline irrigations (control group). A clinical periodontal examination at baseline moment and after 3 months was performed. The parameters considered for analysis were oral hygiene index (IHI), bleeding on probing score (BoP), periodontal pocket probing depth (PD), gingival recession (GR) and clinical attachment level (CAL). 72 sites were included in the analysis, the site with the highest PD/quadrant for each patient. Data were analyzed using GraphPad Prism version 8.0.1 (GraphPad Software Inc., La Jolla, CA, USA). p&lt;0.05 was set as statistical significance level. Outcomes. Eighteen periodontitis patients were treated. All clinical parameters improved at re-evaluation, compared to baseline, both in experimental and control group. The differences were statistically significant in terms of IHI, BoP and PD reduction. At re-evaluation, there were no statistically significant differences between periodontal parameters registered in the experimental and control sites. Conclusions. The present study failed to prove an adjunctive clinical benefit of the antiseptic product in the nonsurgical treatment of periodontitis. These results support the gold standard role of subgingival mechanical instrumentation in the periodontitis’ therapeutic protocol.

Integration of fundamental frequency and voice-onset-time to voicing categorization: Listeners with normal hearing and bimodal hearing configurations.

This study investigates the integration of word-initial fundamental frequency (F0) and voice-onset-time (VOT) in stop voicing categorization for adult listeners with normal hearing (NH) and unilateral cochlear implant (CI) recipients utilizing a bimodal hearing configuration [CI + contralateral hearing aid (HA)]. Categorization was assessed for ten adults with NH and ten adult bimodal listeners, using synthesized consonant stimuli interpolating between /ba/ and /pa/ exemplars with five-step VOT and F0 conditions. All participants demonstrated the expected categorization pattern by reporting /ba/ for shorter VOTs and /pa/ for longer VOTs, with NH listeners showing more use of VOT as a voicing cue than CI listeners in general. When VOT becomes ambiguous between voiced and voiceless stops, NH users make more use of F0 as a cue to voicing than CI listeners, and CI listeners showed greater utilization of initial F0 during voicing identification in their bimodal (CI + HA) condition than in the CI-alone condition. The results demonstrate the adjunctive benefit of acoustic hearing from the non-implanted ear for listening conditions involving spectrotemporally complex stimuli. This finding may lead to the development of a clinically feasible perceptual weighting task that could inform clinicians about bimodal efficacy and the risk-benefit profile associated with bilateral CI recommendation.

High-Vacuum Drainage System in Percutaneous Image-Guided Thoracocentesis for Complex Pleural Effusions

Abstract Purpose Our retrospective study is aimed to analyze the efficacy and outcomes between high-vacuum suction drain (HVSD) over passive drainage in the setting of percutaneous image-guided thoracocentesis, with a secondary aim to determine if preprocedural computed tomography (CT) can aid decision-making. Materials and Methods Clinical and imaging details of patients using HVSD between November 2012 and October 2018, who had a preceding CT within a month before drainage, were collated. The control group was selected from patients who had thoracocentesis with passive drainage performed between November 2017 and October 2018. Cases where HVSD was the sole device were compared with those using only a chest bottle. Results The HVSD was the only device in 17 cases compared to chest bottle in 47 cases. Mean duration being on a drain for these two arms were 5.5 and 7.3 days, respectively (p = 0.170). Fewer from the HVSD arm needed a repeat procedure (p = 0.424). Patients in the HVSD arm had significantly smaller volumes (p = 0.013) of higher density (p = 0.016), associated with a more encapsulating wall (p = 0.013) but not septations (p = 0.922). Density of contents on CT was useful in distinguishing between straw-colored effusion versus hemoserous fluid or pus (p = 0.008). Conclusions HVSD was not inferior to the chest bottle in the setting of thoracocentesis. Considering its potential adjunctive benefits, it should be an option for draining smaller volume complex effusions. Due to poor correlation with preprocedural CT, decision to insert a HVSD should be made by the procedurist at the time of thoracentesis.

PSAT097 Patient Preference Research: Preferred Adjunctive Medication Attributes of Adult Patients with Classic Congenital Adrenal Hyperplasia

Abstract Background People with classic congenital adrenal hyperplasia (CAH) often require supraphysiologic doses of glucocorticoids (e.g., hydrocortisone, dexamethasone) to treat cortisol deficiency and excess androgen production. Healthcare providers and patients continually try to balance androgen control with side effects from supraphysiologic glucocorticoids. This study aimed to understand the preferences of adults with classic CAH regarding benefits of a potential new adjunctive medication that may provide better androgen control and allow for lower glucocorticoid doses. Methods Discrete choice experiment (DCE) methodology was used to calculate the relative stated preferences for the additional therapy's hypothetical benefits (attributes). Seven attributes were developed for the DCE after review of relevant data and qualitative literature, interviews with eight adults with classic CAH and input from two endocrinologists. The online DCE survey was piloted via interviews with three adults with classic CAH and a soft launch, which confirmed survey content and functioning. Preference data and subgroup differences were analyzed using conditional logit and scale assessment modelling, respectively. Results US adults with classic CAH (N=118, 75% female, age 19–69) valued avoidance of glucocorticoid-induced weight gain by twice the magnitude of other treatment attributes (all coefficients p&amp;lt;0.001 compared to baseline levels of no avoidance/decrease/improvement): complete avoidance of weight gain from glucocorticoids (1.109); moderate decrease in risk of developing health conditions from long-term glucocorticoids: type 2 diabetes (0.540), osteopenia, osteoporosis, fractures (0.521) and cardiovascular disease (0.502); moderate improvement in: fatigue (0.439), fertility (0.437) and excessive body hair (females only) and acne (0.410). Avoidance of glucocorticoid-induced weight gain remained the most preferred attribute across all subgroup analyses. Avoidance of glucocorticoid-induced weight gain was relatively much more important to females (n=89) than males (n=28) and participants with a body mass index ≥30 (n=70) than &amp;lt;30 (n=48). Improvement in fertility was more important to males than females, was valued by participants aged 18–45 (n=82) but was not a significant preference in participants &amp;gt;45 (n=36) and was relatively more important to participants with fertility problems (n=31) than without (n=87). Improvement in hirsutism and acne was highly valued by participants with excessive hair growth (n=38) but had the lowest preference among those without (n=80). Improvement in fatigue was a significant preference for participants with energy problems (n=73) but was not significant for those without (n=45). Conclusions The strong and consistent preference for avoiding glucocorticoid-induced weight gain suggests that patients with classic CAH would most value a novel adjunctive therapy that helps mitigate glucocorticoid-induced weight gain. In relation to other potential adjunctive therapy benefits, reduced risk of glucocorticoid-driven side effects may be valued more than improvement in fatigue or androgen-driven adverse events (fertility and hirsutism/acne). However, subgroup analyses indicated that individuals’ characteristics impact their treatment preferences and priorities, after avoidance of glucocorticoid-induced weight gain. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Deferral of Coronary Revascularization in Patients With Reduced Ejection Fraction Based on Physiological Assessment: Impact on Long-Term Survival.

Background Deferring revascularization in patients with nonsignificant stenoses based on fractional flow reserve (FFR) is associated with favorable clinical outcomes up to 15 years. Whether this holds true in patients with reduced left ventricular ejection fraction is unclear. We aimed to investigate whether FFR provides adjunctive clinical benefit compared with coronary angiography in deferring revascularization of patients with intermediate coronary stenoses and reduced left ventricular ejection fraction. Methods and Results Consecutive patients with reduced left ventricular ejection fraction (≤50%) undergoing coronary angiography between 2002 and 2010 were screened. We included patients with at least 1 intermediate coronary stenosis (diameter stenosis ≥40%) in whom revascularization was deferred based either on angiography plus FFR (FFR guided) or angiography alone (angiography guided). The primary end point was the cumulative incidence of all-cause death at 10 years. The secondary end point (incidence of major adverse cardiovascular and cerebrovascular events) was a composite of all-cause death, myocardial infarction, any revascularization, and stroke. A total of 840 patients were included (206 in the FFR-guided group and 634 in the angiography-guided group). Median follow-up was 7 years (interquartile range, 3.22-11.08 years). After 1:1 propensity-score matching, baseline characteristics between the 2 groups were similar. All-cause death was significantly lower in the FFR-guided group compared with the angiography-guided group (94 [45.6%] versus 119 [57.8%]; hazard ratio [HR], 0.65 [95% CI, 0.49-0.85]; P<0.01). The rate of major adverse cardiovascular and cerebrovascular events was lower in the FFR-guided group (123 [59.7%] versus 139 [67.5%]; HR, 0.75 [95% CI, 0.59-0.95]; P=0.02). Conclusions In patients with reduced left ventricular ejection fraction, deferring revascularization of intermediate coronary stenoses based on FFR is associated with a lower incidence of death and major adverse cardiovascular and cerebrovascular events at 10 years.

Stewardship of COVID-19 volunteers by nested trial design

Stewardship of COVID-19 volunteers by nested trial design