OBJECTIVE:Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes, yet its effects in singleton pregnancies conceived via assisted reproductive technology (ART) remain unclear. This study evaluated the association between GDM and maternal and fetal outcomes in this population. METHODS:This retrospective study used the U.S. Nationwide Inpatient Sample 2008-2020 to identify singleton pregnancies conceived via ART. Propensity-score matching was performed to balance baseline characteristics between women with and without GDM. Logistic regression assessed associations between GDM and adverse maternal and fetal outcomes. RESULTS:After matching, 9,625 women were included (1,925 with GDM and 7,700 without GDM). GDM was associated with higher odds of preeclampsia (odds ratio [OR] = 1.24, 95% confidence interval [CI]: 1.03-1.50), placenta previa (OR = 1.34, 95% CI: 1.08-1.66), cesarean delivery (OR = 1.30, 95% CI: 1.18-1.44), induction of labor (OR = 1.14, 95% CI: 1.02-1.28), extended hospital stay (OR = 1.48, 95% CI: 1.24-1.76), preterm birth (OR = 1.30, 95% CI: 1.10-1.53), and large for gestational age/fetal macrosomia (OR = 1.54, 95% CI: 1.26-1.90). Stratified analyses showed generally similar associations across subgroups, while formal interaction analyses identified significant interactions for selected outcomes. CONCLUSION:GDM was significantly associated with adverse maternal and fetal outcomes in singleton pregnancies conceived via ART. These findings highlight the importance of vigilant clinical monitoring for complications such as preeclampsia, excessive fetal growth, preterm birth, and delivery-related complications in this high-risk population.
OBJECTIVE:Continuous glucose monitoring (CGM) offers real-time glucose data that may improve dysglycemia detection in critically ill patients; however, evidence supporting its clinical effectiveness in the intensive care unit (ICU) remains limited. The objective of this study was to evaluate whether a nurse-driven hybrid continuous glucose monitoring (CGM) plus point-of-care (POC) validation protocol improves glycemic outcomes compared with standard POC monitoring alone among medical ICU patients receiving continuous intravenous (IV) insulin. METHODS:In this single-center prospective intervention cohort study, 100 MICU patients receiving continuous IV insulin were monitored using a hybrid CGM+POC protocol and compared with 100 matched historical controls. The primary outcome was % time in glucose range (70-180 mg/dL) during continuous IV insulin therapy, calculated using POC values (at least every 4 hours) for between-group comparisons. Secondary outcomes included % time in additional glucose ranges, hyperglycemia (>250 and >400 mg/dL), and hypoglycemia (<70 and <54 mg/dL). RESULTS:Compared with controls, CGM-managed patients achieved an increased time in range (76%±18 vs 64%±21; p<0.001) with persistent improvement after adjusting for confounders and marked reductions in severe hyperglycemia (>250 mg/dL: 6%±11 vs 17%±18; >300 mg/dL: 2.7±0.6% vs 11.3±1.4%; p<0.001 for both). Hypoglycemic events were infrequent and similar between groups. A total of 3,590 temporally matched CGM-POC pairs were available for analysis. CONCLUSION:In this prospective MICU cohort, real-time hybrid CGM use improved glycemic control and reduced severe hyperglycemia without increasing hypoglycemia, supporting further evaluation of structured CGM integration in critical care practice.
OBJECTIVE:The 2025 American Thyroid Association (ATA) guidelines for differentiated thyroid cancer (DTC) expanded and refined the risk stratification system (RSS). The extent of patient redistribution across risk categories and the clinicopathologic drivers of reclassification remain unclear. METHODS:We conducted a retrospective study of adult DTC patients who underwent thyroid surgery at a tertiary cancer center between 1999 and 2025. The 2015 and 2025 ATA RSS criteria were applied to the same cohort using R-based algorithms. Patient migration across risk categories and clinicopathologic factors associated with reclassification were analyzed descriptively. RESULTS:A total of 843 patients with DTC (papillary, follicular, oncocytic, high grade, poorly differentiated) were included in the study. Most patients with DTC (669; 79.4%) remained in the same risk category, while 174 (20.6%) migrated to a different one. Among 2015 ATA low-risk patients, 105 (12.6%) were reclassified to higher-risk categories by the 2025 ATA RSS, including 84 to the low-intermediate group and 21 to the intermediate-high group. Additionally, 69 patients (8.2%) were reclassified from the 2015 intermediate-risk category to the 2025 high-risk category. Consequently, under the 2025 ATA RSS, the proportion of low-risk patients decreased by 29.7%, whereas the 2025 ATA intermediate-risk (low-intermediate and intermediate-high) and high-risk groups increased by 9.6% and 8.2%, respectively. No downward reclassification was observed. CONCLUSION:Application of the 2025 ATA RSS resulted in upward reclassification. The clinical implications of this redistribution remain to be validated, and further work is needed to correlate the revised risk categories with recurrence rates and disease-specific outcomes.
Artificial intelligence (AI) is transforming thyroid care, with applications spanning ultrasound risk stratification, cytopathology, histopathology, radiogenomics, prognosis, intraoperative parathyroid identification, thyroid eye disease, functional thyroid disorders, and clinical decision support. This narrative review summarizes the evidence and barriers to adoption. Ultrasound-based AI for thyroid nodule risk stratification is the most mature application. Deep learning-assisted cytopathology and intraoperative frozen-section analysis show promise in resolving indeterminate Bethesda nodules. Radiomics and digital pathology can non-invasively predict BRAF V600E, RAS, fusion alterations, and inflammatory subtypes, although most tools remain investigational. Machine learning refines recurrence prediction beyond conventional risk stratification and informs radioiodine response and dose selection. In thyroid and parathyroid surgery, AI-augmented near-infrared autofluorescence is advancing toward real-time intraoperative gland identification. AI also supports thyroid eye disease activity assessment and glucocorticoid response prediction, and emerging tools target hyper- and hypothyroidism, including differentiation of Graves' disease from thyroiditis and levothyroxine dose optimization. Large language models are improving in patient education but are not approved for diagnostic use and remain prone to fabricated citations and version drift. AI should be regarded as a decision-support adjunct that augments, rather than replaces, endocrinologist judgment, contingent on prospective multicenter validation, equitable access, transparent reporting, and defined reimbursement frameworks.
Hyperthyroidism in pregnancy most commonly results from gestational transient thyrotoxicosis (GTT), though Graves' disease, and less frequently, toxic nodular disease also occurs. Differentiating these conditions requires integration of clinical findings, trimester-specific thyroid function tests thresholds, and thyroid-stimulating immunoglobulin measurement when autoimmune etiology is suspected. Untreated or inadequately managed maternal overt hyperthyroidism that is not due to GTT is associated with significant maternal and fetal complications, including preeclampsia, thyroid storm, growth restriction, and fetal or neonatal thyrotoxicosis. Graves' disease management requires a delicate balance between achieving maternal euthyroidism and minimizing fetal drug exposure. Propylthiouracil is preferred during the first trimester to reduce teratogenic risk. If antithyroid drug (ATD) therapy is still required beyond 16 weeks of gestation, the decision to continue on propylthiouracil or switch to methimazole should be guided by shared decision-making between the patient and clinician. The use of the lowest effective ATD dose and close biochemical monitoring remain fundamental principles. Beta-adrenergic blockade may provide short-term symptomatic relief, whereas iodides are reserved for selected cases intolerant to ATDs. Thyroidectomy is typically reserved for patients with refractory hyperthyroidism or contraindications to ATDs and is preferably performed during the second trimester of pregnancy. Postpartum relapse of Graves' disease is common. Methimazole is considered safe during lactation at low doses, with no adverse effects on infant growth or neurodevelopment, while radioactive iodine therapy remains contraindicated. Collectively, contemporary evidence emphasizes early diagnosis, individualized therapy, and multidisciplinary care as central to optimizing maternal and fetal outcomes in hyperthyroidism during the reproductive years.
Objective This study aimed to observe the effect of vitamin D combined with probiotic-assisted insulin pump on glucose-lipid metabolism, intestinal flora and pregnancy outcome in gestational diabetes mellitus (GDM). Methods A total of 150 GDM patients were randomized into the study and control groups (n=75 each). All patients were admitted to the hospital to receive diet, nutrition and exercise guidance, the control group was given insulin aspart pump therapy plus vitamin D, and the study group received insulin aspart pump therapy plus vitamin D and Viable Bifidobacterium Tablets. Outcomes included glycemic and lipid metabolic indices, gut microbiota changes, standard-reaching rates of blood glucose, and adverse pregnancy outcomes. Results After treatment, levels of HDL-C, counts of Bifidobacterium and Lactobacillus were increased in both groups (P < 0.05), and levels of FINS, FPG, 2hPG, HbA1c, LDL-C, TC, TG, counts of Coccidioides, Enterobacteriaceae, and Saccharomycetes were all reduced (P < 0.05); and all of them were improved in the study group versus the control group (P < 0.05). The study group also showed higher standard-reaching rates of blood glucose (96.00% vs. 84.00%) and lower overall incidence of adverse pregnancy outcomes (14.67% vs. 33.33%) than the control group (all P < 0.05). Conclusion Compared with insulin pump plus vitamin D therapy, the addition of probiotics may improve blood glucose and lipid metabolism in GDM patients, maintain intestinal microbiota balance, and reduce the risk of adverse pregnancy outcomes. Further multicenter, large sample size, double blind and placebo-controlled studies are needed to confirm these findings.
OBJECTIVE:To determine whether glycemic benefits of the MiniMed 780G Advanced Hybrid Closed-Loop system are sustained over 2 years in youth with type 1 diabetes, and to identify outcome predictors. METHODS:This prospective multicenter study collected continuous glucose monitoring (CGM) and clinical data at 1, 3, 6, 12, and 24 months in 96 children and adolescents with type 1 diabetes. Outcomes included hemoglobin A1c, CGM metrics, composite glycemic control score, glycemia risk index, composite CGM index, SmartGuard use, and anthropometric changes, analyzed by repeated-measures linear mixed models. RESULTS:Hemoglobin A1c and time in range were maintained from 12 to 24 months, but time below range increased (1.8-2.5%, P = .015). Composite targets were rarely met: CGC by 14.6%, best GRI by 9.4%, best COGI by 10.4%. SmartGuard use declined from 91.3% to 82.7% (P = .013); lower socioeconomic position and lower 12-month SmartGuard use were independently associated with this decline. Girls had lower glycemic variability than boys and greater BMI z-score increase. Five DKA and 2 severe hypoglycemia events occurred, all device-or behavior-related. CONCLUSION:The 780G Advanced Hybrid Closed-Loop system sustained meaningful glycemic benefits over 2 years, yet most youth failed to achieve optimal composite glycemic control. SmartGuard decline during the second year suggests the 12-month visit as a candidate checkpoint for monitoring device engagement, warranting evaluation in a future interventional trial.
INTRODUCTION:Adolescent boys presenting late with short stature and advanced bone age (BA/CA >1) have guarded height outcomes. Whether aromatase inhibitors (AI) or GnRH analogs (GnRHa) combined with growth hormone (GH) improve height is unknown. We compared AI+GH, GnRHa+GH, AI alone, and GH alone in boys with reduced predicted adult height and advanced bone age. METHODS:We conducted a PROSPERO-registered systematic review and Bayesian network meta-analysis, reported per PRISMA-NMA, with a prespecified letrozole-versus-anastrozole sensitivity analysis; certainty was rated using CINeMA. Eight observational studies (651 boys) were included. Outcomes were change in predicted adult height (ΔPAH; primary), final adult height, height standard deviation score (SDS) for chronological and bone age, bone-age advancement ratio (ΔBA/ΔCA), and hyperuricemia, ranked by SUCRA with mean differences (95% credible intervals). RESULTS:AI+GH ranked first for ΔPAH (SUCRA 0.99) and was the only regimen significantly superior to GH, improving ΔPAH by +3.58 cm (1.83-5.14) and final adult height by +2.70 cm (0.12-5.16). AI+GH also ranked highest for height SDS for chronological age and ΔBA/ΔCA and tied with GnRHa+GH for height SDS for bone age. GnRHa+GH ranked second but did not differ from GH. Hyperuricemia was more frequent with AI+GH (47%) than with GH or GnRHa+GH (0%). CINeMA certainty was very low across comparisons. DISCUSSION:In adolescent boys with advanced bone age, AI+GH was the highest-ranked strategy for improving predicted and final adult height, ahead of GnRHa+GH and monotherapy, although very low-certainty evidence warrants confirmatory trials.
Thyroid artery embolization (TAE) is an emerging minimally invasive treatment for benign and select malignant thyroid diseases. This review summarizes current evidence and presents expert consensus recommendations from the North American Society for Interventional Thyroidology regarding patient selection, indications, technique, safety, outcomes, and the role of TAE in contemporary thyroid disease management. Recommendations were developed through multidisciplinary expert review of the literature, including comparisons with surgery, thermal ablation, and radioactive iodine therapy. TAE is particularly effective for large-volume thyroid disease (>30 mL nodules and >50 mL goiters) and substernal extension, achieving 32% to 73% volume reduction at 6 months with improvement in compressive symptoms and cosmesis. In Graves disease and toxic multinodular goiter, euthyroidism rates exceed 70%, with reported durability up to 50 months. Preoperative TAE may reduce operative time and blood loss. Most adverse events are mild and self-limited, and serious complications are rare. TAE represents a safe and effective option for selected patients with symptomatic thyroid disease and may also have roles in hyperthyroidism and preoperative management. Further studies are needed to standardize technique and define its position relative to established therapies.
This paper is based on the Keynote Address at the 2026 American Association of Clinical Endocrinology (AACE) Annual Meeting on Nutrition and Chronic Disease. Nutrition is the interaction of diet and metabolism though conventional focus is on the dietary aspect. When applied, the driver-based chronic disease paradigm re-interprets abnormal nutrition as a portfolio of preventable metabolic disorders. This paradigm comprises network analysis, key mechanistic drivers, staged progression, nonbiological factors, and early/sustainable prevention. To this end, the conceptualization, operationalization, and empirical implementation/validation of the malnutrition-based chronic disease (MBCD) model address the triple burden of undernutrition (starvation, cachexia, and other wasting syndromes) + overnutrition (eg, overweight/obesity, ectopic fat, insulin resistance, and cardiometabolic risks) + micronutrient derangements (deficiencies and toxicities). The MBCD model and critical role of structured lifestyle medicine centers on nutrition as an early and sustainable strategy to prevent chronic disease complications, disability, and higher cost-/risk-related interventions, while also promoting health (optimal and personalized metrics, low symptom burden, and happiness) and disambiguating a historically confusing lexicon. The MBCD model also addresses personalization by incorporating structural, social, and cultural determinants of health, thus expanding the range of available preventive care targets. Ultimately, the deliverable of this approach is through iterative optimization to close research, knowledge, and practice gaps. This new paradigm finds its roots in the legacy of AACE white papers that have emphasized nutrition-oriented pathophysiology in chronic disease states such as diabetes and obesity. Indeed, AACE is poised to transform nutritional medicine and endocrine care of chronic disease to tackle current contemporary healthcare imperatives on a global scale.
Despite major advances in therapeutics, many adults with type 2 diabetes do not achieve recommended glycemic targets, driven by progressive beta-cell dysfunction and persistent therapeutic inertia. Insulin therapy is commonly delayed for years, exposing patients to prolonged hyperglycemia and substantially increasing complication risks. Although automated insulin delivery (AID) systems have transformed outcomes for people with type 1 diabetes, their adoption in type 2 diabetes has been limited. Emerging evidence and recent updates to the American Diabetes Association Standards of Care now support AID as the preferred insulin delivery method for adults with type 2 diabetes on multiple daily injections of insulin or for whom basal-only insulin is not sufficient to achieve glycemic targets, reflecting a paradigm shift toward addressing the burdens and limitations of manual insulin delivery. Randomized and real-world studies demonstrate that AID systems significantly improve A1C and time in range while minimizing hypoglycemia, without increasing treatment complexity or patient burden. By dynamically adapting insulin delivery to real-time continuous glucose monitoring data, AID mitigates common barriers to intensification, including fear of hypoglycemia and increased regimen complexity associated with multiple daily injections. In addition, AID enables more efficient diabetes care through standardized glucose reporting, remote data review, and team-based management. Together, these advances position AID as a practical and effective strategy to overcome long-standing therapeutic inertia in type 2 diabetes. Earlier consideration of AID during insulin intensification could improve glycemic outcomes, reduce diabetes-related complications, decrease cognitive burden, and modernize insulin delivery for people living with type 2 diabetes.
OBJECTIVES:To compare cardiovascular outcomes associated with metabolic and bariatric surgery (MBS) vs semaglutide therapy among adults with obesity, stratified by type 2 diabetes mellitus (T2DM) status. METHODS:This retrospective cohort study used the US Collaborative Network within TriNetX. Adults with obesity who initiated semaglutide therapy or underwent sleeve gastrectomy or Roux-en-Y gastric bypass between January 2018 and January 2025 were propensity score matched separately according to T2DM history. The primary outcome was a composite of coronary events, cerebrovascular events, heart failure, and cardiac arrest during follow-up of up to 5 years. Sensitivity analyses varied the follow-up horizon, postindex encounter requirements, semaglutide refill requirements, and the start of follow-up. RESULTS:After matching, each treatment group included 11 466 patients without T2DM and 7327 patients with T2DM. MBS was associated with a lower risk of the composite cardiovascular outcome than semaglutide therapy among patients without T2DM (4.4% vs 6.6%; hazard ratio [HR], 0.402; 95% CI, 0.356-0.454) and with T2DM (9.0% vs 14.6%; HR, 0.421; 95% CI, 0.381-0.465). MBS was also associated with lower risks of coronary events, cerebrovascular events, and heart failure in both strata. The relative differences were greatest for heart failure (HR, 0.293 without a history of T2DM; HR, 0.346 with a history of T2DM). Findings remained directionally consistent across subgroup and sensitivity analyses. CONCLUSIONS:Among adults with obesity, MBS was associated with lower cardiovascular risk than semaglutide therapy, regardless of T2DM history. These findings provide real-world comparative evidence to inform individualized discussions of surgical and pharmacologic obesity treatment options.
OBJECTIVE:Pheochromocytomas and paragangliomas (PPGLs) are associated with profound metabolic and cardiovascular alterations. Chronic catecholamine excess induces a hypermetabolic and catabolic state that may affect skeletal muscle and adipose tissue distribution, potentially contributing to metabolic comorbidities. However, data regarding body composition changes in patients with PPGLs remain limited. Thus, we aimed to evaluate body composition differences between patients with PPGLs and age- and sex-matched patients with non-functioning adrenal tumors (NFATs), and to explore their association with metabolic comorbidities. METHODS:We conducted a retrospective study including 44 patients with histologically confirmed PPGLs and 88 age- and sex-matched patients with NFATs. Contrast-enhanced computed tomography (CT) scans obtained at diagnosis were analyzed using semi-automated software enabling two-dimensional (2D) and three-dimensional (3D) body composition assessment. RESULTS:Patients with PPGLs showed significantly higher muscle-related parameters compared with NFATs, including muscle mass percentage, lean mass percentage, and muscle density in both 2D and 3D analyses (p<0.05). Conversely, adipose tissue compartments were consistently reduced in PPGLs. Intramuscualr adipose tissue (IMAT) area and index were significantly lower in the 2D analysis, with increased density (p<0.01) while IMAT volume and mass were reduced and density increased in the 3D analysis (p<0.05). Muscle quality was slightly but significantly better in the PPGLs group (p<0.01). Similarly, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) parameters, including area, volume, and mass, were significantly lower in patients with PPGLs, in both, 2D and 3D analysis (p<0.05) whereas VAT density was significantly higher (p<0.01, p<0.001 respectively). In multivariate analyses adjusted for age, sex, hormone secretion, alcohol consumption, tobacco exposure and BMI, SAT was independently associated with hypertension in the PPGL group. In contrast, several muscle- and adipose tissue-related parameters were independently associated with hypertension and impaired glucose metabolism in patients with NFATs. CONCLUSION:Patients with PPGLs exhibit a distinct body composition profile characterized by preserved muscle mass and reduced adipose tissue compartments. Despite these marked differences, body composition parameters were not independently associated with metabolic comorbidities in PPGLs, suggesting that catecholamine excess may play a predominant role in metabolic dysfunction beyond adipose tissue distribution alone.
INTRODUCTION:Quality of life (QoL) is impaired in acromegaly, particularly in patients with active disease. Improvement of symptoms following hormonal normalization is expected to positively affect QoL. OBJECTIVE:To assess whether earlier and more effective disease control, achieved in the ACROFAST study, is associated with improvements in AcroQoL scores and symptom burden evaluated by the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) questionnaire. METHODS:AcroQoL and PASQ outcomes were analyzed within the ACROFAST study timeframe, comparing controlled and uncontrolled patients. Assessments were performed at baseline, 6 months, and 12 months. RESULTS:No differences in global AcroQoL scores were observed between treatment arms. However, hormonally controlled patients presented better results in the appearance sub-dimension of the AcroQoL (59 ± 19 vs 45 ± 20 points; P = .04) and in PASQ score (15 ± 12 vs 23 ± 10 points; P = .01) at the end of the study. Paired analyses confirmed improvement in PASQ among controlled patients, and linear mixed-effects modelling further demonstrated a reduction over time (estimated marginal means: 19, 14, 14), while scores remained stable in uncontrolled patients. Sub-group analysis revealed that women had worse scores for both QoL and symptoms tests. Severity of symptoms correlated with QoL. CONCLUSION:Biochemical control is associated with improved symptoms and appearance-related QoL. A personalized approach, which is more effective achieving biochemical control than the standard one, may provide additional patient centered benefits, even if this study only provides indirect evidence. Women exhibited poorer QoL despite similar control rates, suggesting unmet supportive care needs in this subgroup.
OBJECTIVES:No systematic review and meta-analysis has analyzed the safety and efficacy of glucagon like peptide-1 receptor agonism-based therapies (GLP1RA-BTs) in people with end stage renal disease (ESRD) [GFR<15 ml/min/1.73 m2 or on renal replacement therapy]. Hence this systematic review and meta-analysis analyzed the safety and efficacy of GLP1RA-BT in ESRD. METHODS:Electronic databases were searched for articles evaluating the use of GLP1RA-BT in ESRD. Primary outcome was mean reduction in body weight from baseline following treatment with GLP1RA-BT. Secondary outcomes were changes in body mass index (BMI), glycaemia, and safety profile. RESULTS:Data from 388 patients [semaglutide(266), liraglutide(66), dulaglutide(47), and tirzepatide(9); 19 studies] with ESRD (91.5% on renal replacement therapy) having baseline weight, BMI, and glycated hemoglobin of 97.7 ± 23.8 kg, 34.4 ± 6.8kg/m2, and 7.26 ± 1.53%, respectively were analyzed. Weight reduction with semaglutide after 3-, 6-, and 12-months therapy were -3.09 kg (95% confidence interval [CI]: -5.95, -0.24; I2 = 58.1%), -3.68 kg (95% CI: -5.71, -1.65; I2 = 0.0%), and -7.00 kg (95% CI: -11.38, -2.61; I2 = 79.2%), respectively. BMI reduction with semaglutide after 3-, 6-, and 12-months therapy were -1.42 kg/m2 (95% CI: -2.92, 0.09; I2 = 0.0%), -1.26 kg/m2 (95% CI: -1.90, -0.62; I2 = 0.0%), and -3.09 kg/m2 (95% CI: -5.28, -0.89; I2 = 95.9%), respectively. Pooled glycated hemoglobin reduction with semaglutide after 6 and 12 months of therapy were -0.50% (95% CI: -1.20, 0.20; I2 = 0.0%) and -0.75% (95% CI: -1.07, -0.43; I2 = 61.6%), respectively. Pooled body-weight reduction with liraglutide after 3 and 6 months therapy were -2.24 kg (95% CI: -7.73, 3.26; I2 = 0.0%) and -4.50 kg (95% CI: -11.26, 2.27; I2 = 0.0%), respectively. With semaglutide, total adverse events (AEs) occurred in 44% patients (95% CI: 24%, 66%; I2 = 58.3%). Gastrointestinal AEs were observed in 39% (95% CI: 25%, 55%; I2 = 48.8%), including nausea in 36% (95% CI: 3%, 91%; I2 = 73.6%) and vomiting in 13% (95% CI: 2%, 53%; I2 = 0.0%). Hypoglycaemia occurred in 9% (95% CI: 0%, 82%; I2 = 0.0%). Discontinuation due to AEs was observed in 9% (95% CI: 4%, 20%; I2 = 60.3%). CONCLUSION:GLP1RA-BT specifically semaglutide, may be considered for use in ESRD. The results are primarily hypothesis generating, and prospective RCTs are urgently needed.
