Enhanced predictive validity of integrative models for refractory hyperthyroidism considering baseline and early therapy characteristics: a prospective cohort study.

BACKGROUND: A subset of Graves' disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics and early therapy indicators in identifying high risk individuals is an area worth exploration. METHODS: A prospective cohort study (2018-2022) involved 597 newly diagnosed adult GD patients undergoing methimazole (MMI) treatment. Baseline characteristics and 3-month therapy parameters were utilized to develop predictive models for refractory GD, considering antithyroid drug (ATD) dosage regimens. RESULTS: Among 346 patients analyzed, 49.7% developed ATD-refractory GD, marked by recurrence and sustained Thyrotropin Receptor Antibody (TRAb) positivity. Key baseline factors, including younger age, Graves' ophthalmopathy (GO), larger goiter size, and higher initial free triiodothyronine (fT3), free thyroxine (fT4), and TRAb levels, were all significantly associated with an increased risk of refractory GD, forming the baseline predictive model (Model A). Subsequent analysis based on MMI cumulative dosage at 3 months resulted in two subgroups: a high cumulative dosage group (average ≥ 20 mg/day) and a medium-low cumulative dosage group (average < 20 mg/day). Absolute values, percentage changes, and cumulative values of thyroid function and autoantibodies at 3 months were analyzed. Two combined predictive models, Model B (high cumulative dosage) and Model C (medium-low cumulative dosage), were developed based on stepwise regression and multivariate analysis, incorporating additional 3-month parameters beyond the baseline. In both groups, these combined models outperformed the baseline model in terms of discriminative ability (measured by AUC), concordance with actual outcomes (66.2% comprehensive improvement), and risk classification accuracy (especially for Class I and II patients with baseline predictive risk < 71%). The reliability of the above models was confirmed through additional analysis using random forests. This study also explored ATD dosage regimens, revealing differences in refractory outcomes between predicted risk groups. However, adjusting MMI dosage after early risk assessment did not conclusively improve the prognosis of refractory GD. CONCLUSION: Integrating baseline and early therapy characteristics enhances the predictive capability for refractory GD outcomes. The study provides valuable insights into refining risk assessment and guiding personalized treatment decisions for GD patients.

Baseline characteristics from a 3-year longitudinal study to phenotype subjects with COPD: the FOOTPRINTS study.

BACKGROUND: FOOTPRINTS® is a prospective, longitudinal, 3-year study assessing the association between biomarkers of inflammation/lung tissue destruction and chronic obstructive pulmonary disease (COPD) severity and progression in ex-smokers with mild-to-severe COPD. Here, we present baseline characteristics and select biomarkers of study subjects. METHODS: The methodology of FOOTPRINTS® has been published previously. The study population included ex-smokers with a range of COPD severities (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages 1-3), ex-smokers with COPD and alpha-1-antitrypsin deficiency (A1ATD) and a control group of ex-smokers without airflow limitation (EwAL). At study entry, data were collected for: demographics, disease characteristics, history of comorbidities and COPD exacerbations, symptoms, lung function and volume, exercise capacity, soluble biomarkers, and quantitative and qualitative computed tomography. Baseline data are presented with descriptive statistical comparisons for soluble biomarkers in the individual GOLD and A1ATD groups versus EwAL. RESULTS: In total, 463 subjects were enrolled. The per-protocol set comprised 456 subjects, mostly male (64.5%). The mean (standard deviation) age was 60.7 (6.9) years. At baseline, increasing pulmonary symptoms, worse lung function, increased residual volume, reduced diffusing capacity of the lung for carbon monoxide (DLco) and greater prevalence of centrilobular emphysema were observed with increasing disease severity amongst GOLD 1-3 subjects. Subjects with A1ATD (n = 19) had similar lung function parameters to GOLD 2-3 subjects, a high residual volume comparable to GOLD 3 subjects, and similar air trapping to GOLD 2 subjects. Compared with EwAL (n = 61), subjects with A1ATD had worse lung function, increased residual volume, reduced DLco, and a greater prevalence of confluent or advanced destructive emphysema. The soluble inflammatory biomarkers white blood cell count, fibrinogen, high-sensitivity C-reactive protein and plasma surfactant protein were higher in GOLD 1-3 groups than in the EwAL group. Interleukin-6 was expressed less often in EwAL subjects compared with subjects in the GOLD and A1ATD groups. Soluble receptor for advanced glycation end product was lowest in GOLD 3 subjects, indicative of more severe emphysema. CONCLUSIONS: These findings provide context for upcoming results from FOOTPRINTS®, which aims to establish correlations between biomarkers and disease progression in a representative COPD population. TRIAL REGISTRATION NUMBER: NCT02719184, study start date 13/04/2016.

Characteristics of baseline frequency data in spinal RCTs do not suggest widespread non-random allocation.

BACKGROUND: Recent signs of fraudulent behaviour in spine RCTs have queried the integrity of trials in the field. RCTs are particularly important due to the weight they are accorded in guiding treatment decisions, and thus, ensuring RCTs' reliability is crucial. This study investigates the presence of non-random baseline frequency data in purported RCTs published in spine journals. METHODS: A PubMed search was performed to obtain all RCTs published in four spine journals (Spine, The Spine Journal, the Journal of Neurosurgery Spine, and European Spine Journal) between Jan-2016 and Dec-2020. Baseline frequency data were extracted, and variable-wise p values were calculated using the Pearson Chi-squared test. These p values were combined for each study into study-wise p values using the Stouffer method. Studies with p values below 0.01 and 0.05 and those above 0.95 and 0.99 were reviewed. Results were compared to Carlisle's 2017 survey of anaesthesia and critical care medicine RCTs. RESULTS: One hundred sixty-seven of the 228 studies identified were included. Study-wise p values were largely consistent with expected genuine randomized experiments. Slightly more study-wise p values above 0.99 were observed than expected, but a number of these had good explanations to account for that excess. The distribution of observed study-wise p values was more closely matched to the expected distribution than those in a similar survey of the anaesthesia and critical care medicine literature. CONCLUSION: The data surveyed do not show evidence of systemic fraudulent behaviour. Spine RCTs in major spine journals were found to be consistent with genuine random allocation and experimentally derived data.

Baseline characteristics of adults with neurofibromatosis enrolled on a psychosocial randomized controlled trial.

PURPOSE: Neurofibromatosis (NF) is an incurable genetic neurological condition. Psychosocial interventions that promote resiliency are a promising approach to address the high emotional distress and low quality of life (QoL) associated with NF. However, no studies have examined the psychosocial needs of treatment-seeking adults with NF. Our goal was to explore, using data from the largest efficacy trial of a psychosocial intervention for NF, differences in QoL, emotional distress, resiliency, and pain-related outcomes compared to other chronic medical populations and within subtypes (NF1, NF2, schwannomatosis; SCHW). METHODS: Enrolled participants (N = 228) were geographically diverse adults with NF and elevated stress. We performed secondary analysis on baseline measures of QoL, emotional distress, resiliency, and pain-related outcomes. We reported descriptive statistics and normative comparisons to understand the psychosocial characteristics of the overall sample and performed between-group analyses to explore differences within NF type. RESULTS: Our sample endorsed worse QoL, emotional distress, resilience, and pain-related outcomes than similar chronic illness populations. Within NF types, participants with NF1 reported lower QoL and resilience compared to those with NF2. Participants with SCHW reported higher pain intensity than those with NF1. Participants with SCHW reported higher pain interference and lower physical QoL compared to those with NF1 and NF2. CONCLUSIONS: Our findings support the urgent need for psychosocial interventions targeting deficits in QoL, emotional distress, resilience, and pain-related outcomes in adults with NF. We recommend efforts to enhance sample diversity, prepare clinicians to provide high-levels of support, and attune skills training to each NF type. TRIAL REGISTRATION: ClinicalTrials.gov NCT03406208; https://clinicaltrials.gov/ct2/show/NCT03406208 (Archived by WebCite at http://www.webcitation.org/72ZoTDQ6h ).

Baseline characteristics of participants enrolled in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD).

BACKGROUND: We developed the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD) as a subcohort of KNOW-CKD to investigate the different characteristics of pediatric CKD between countries and races. METHODS: Children aged younger than 18 years with stage 1 ~ 5 CKD were recruited at seven major pediatric nephrology centers in Korea. Blood and urine samples, as well as demographic and clinical data, were collected. From 2011 to 2016, 458 children were enrolled, and the baseline profiles of 437 children were analyzed. RESULTS: The median age of the cohort was 10.9 years old, and 68.0% were males. The median estimated glomerular filtration rate was 53.1 mL/min/1.73 m2. The most common etiology of CKD was congenital anomalies of the kidney and urinary tract (42.6%), followed by glomerulopathies (25.6%). CONCLUSION: We report a cross-sectional analysis of the overall baseline characteristics such as age, CKD stage, and underlying kidney disease of the KNOW-Ped CKD. The cohort will be longitudinally followed for ten years. "A higher resolution version of the Graphical abstract is available as Supplementary information."

Randomized clinical trials and real life studies: Comparison of baseline characteristics of patients in oral target therapies for renal cell carcinoma.

INTRODUCTION: Pivotal Randomized Controlled Trials (RCTs) constitute scientific evidence in support of therapeutic choices when a drug is authorized in the market. In RCTs, patients are selected in a rigorous manner, in order to avoid bias that may influence efficacy assessments. Therefore, patients who take the drug in Real Life Studies (RLSs) are not the same as those participating in RCTs, which, in turn, leads to low data transferability from RCTs to RLS. The objective of this study was to evaluate the differences between RCTs and RLS, in terms of patient baseline characteristics. MATERIALS AND METHODS: Our study includes all oral target therapies for RCC (Renal Cell Carcinoma) marketed in Europe before March 31, 2019. For each treatment, we considered both RCTs and RLSs, the former gathered from Summary of Product Characteristics published on the European Medicine Agency (EMA) website, and the latter yielded by our search in relevant literature. For each drug considered, we then compared the baseline characteristics of patients included in the RCT samples with those of the samples included in the RLSs using the Chi-squared and Mann-Whitney tests. RESULTS: We considered six medicines, for a total of 9 pivotal RCTs and 31 RLSs. RCTs reported the same type of patient baseline characteristics, whereas RLSs are more varied in reporting. Some patient baseline characteristics (metastases, previous treatments, etc.) were significantly different between RCTs and RLs. Other characteristics, such as ECOG Performance Status, brain metastases, and comorbidities, liver and kidney failure, are comprised in exclusion criteria of RCTs, though are included in RLS.Discussion and Conclusion: While evaluating equal treatments for the same indications, RCTs and RLSs do not always assess patients with the same characteristics. It would be necessary to produce evidence from RLSs so as to have an idea of treatment effectiveness in patients groups that are not eligible or underrepresented in RCTs.

Baseline characteristics and first-line treatment patterns in patients with HER2-positive metastatic breast cancer in the SystHERs registry.

BACKGROUND: Systemic Therapies for HER2-Positive Metastatic Breast Cancer Study (SystHERs, NCT01615068) was a prospective, observational disease registry designed to identify treatment patterns and clinical outcomes in patients with HER2-positive metastatic breast cancer (MBC) in real-world treatment settings. METHODS: SystHERs enrolled patients aged ≥ 18 years with recently diagnosed HER2-positive MBC. Treatment regimens and clinical management were determined by the treating physician. In this analysis, patients were compared descriptively by first-line treatment, age, or race. Multivariate logistic regression was used to examine the associations between baseline variables and treatment selections. Clinical outcomes were assessed in patients treated with trastuzumab (Herceptin [H]) + pertuzumab (Perjeta [P]). RESULTS: Patients were enrolled from June 2012 to June 2016. As of February 22, 2018, 948 patients from 135 US treatment sites had received first-line treatment, including HP (n = 711), H without P (n = 175), or no H (n = 62) (with or without chemotherapy and/or hormonal therapy). Overall, 68.7% received HP + taxane and 9.3% received H without P + taxane. Patients aged < 50 years received HP (versus H without P) more commonly than those ≥ 70 years (odds ratio 4.20; 95% CI, 1.62-10.89). Chemotherapy was less common in patients ≥ 70 years (68.2%) versus those < 50 years (88.0%) or 50-69 years (87.4%). Patients treated with HP had median overall survival of 53.8 months and median progression-free survival of 15.8 months. CONCLUSIONS: Our analysis of real-world data shows that most patients with HER2-positive MBC received first-line treatment with HP + taxane. However, older patients were less likely to receive dual HER2-targeted therapy and chemotherapy.

Baseline characteristics and comparability of older multimorbid patients with polypharmacy and general practitioners participating in a randomized controlled primary care trial.

OBJECTIVES: Recruiting general practitioners (GPs) and their multimorbid older patients for trials is challenging for multiple reasons (e.g., high workload, limited mobility). The comparability of study participants is important for interpreting study findings. This manuscript describes the baseline characteristics of GPs and patients participating in the 'Optimizing PharmacoTherapy in older multimorbid adults In primary CAre' (OPTICA) trial, a study of optimization of pharmacotherapy for multimorbid older adults. The overall aim of this study was to determine if the GPs and patients participating in the OPTICA trial are comparable to the real-world population in Swiss primary care. DESIGN: Analysis of baseline data from GPs and patients in the OPTICA trial and a reference cohort from the FIRE ('Family medicine ICPC Research using Electronic medical records') project. SETTING: Primary care, Switzerland. PARTICIPANTS: Three hundred twenty-three multimorbid (≥ 3 chronic conditions) patients with polypharmacy (≥ 5 regular medications) aged ≥ 65 years and 43 GPs recruited for the OPTICA trial were compared to 22,907 older multimorbid patients with polypharmacy and 227 GPs from the FIRE database. METHODS: We compared the characteristics of GPs and patients participating in the OPTICA trial with other GPs and other older multimorbid adults with polypharmacy in the FIRE database. We described the baseline willingness to have medications deprescribed of the patients participating in the OPTICA trial using the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. RESULTS: The GPs in the FIRE project and OPTICA were similar in terms of sociodemographic characteristics and their work as a GP (e.g. aged in their fifties, ≥ 10 years of experience, ≥ 60% are self-employed, ≥ 80% work in a group practice). The median age of patients in the OPTICA trial was 77 years and 45% of trial participants were women. Patients participating in the OPTICA trial and patients in the FIRE database were comparable in terms of age, certain clinical characteristics (e.g. systolic blood pressure, body mass index) and health services use (e.g. selected lab and vital data measurements). More than 80% of older multimorbid patients reported to be willing to stop ≥ 1 of their medications if their doctor said that this would be possible. CONCLUSION: The characteristics of patients and GPs recruited into the OPTICA trial are relatively comparable to characteristics of a real-world Swiss population, which indicates that recruiting a generalizable patient sample is possible in the primary care setting. Multimorbid patients in the OPTICA trial reported a high willingness to have medications deprescribed. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT03724539 ), KOFAM (Swiss national portal) ( SNCTP000003060 ), Universal Trial Number (U1111-1226-8013).

[Primary Sjogren's syndrome associated pulmonary arterial hypertension: 20 new cases].

Objective: To describe baseline characteristics of patients with primary Sjogren's syndrome (pSS) with right heart catheterization (RHC)-confirmed pulmonary arterial hypertension (PAH). Methods: This retrospective study included consecutive patients hospitalized with pSS-PAH from Jan.2013 to June.2019 in Tianjin Medical University General Hospital. All patients fulfilled the 2002 revised criteria for pSS proposed by the American-European Consensus Group. PAH was defined according to RHC-based European Society of Cardiology/European Respiratory Society guidelines. Associated variables were described and analyzed. Predictive factors for achieving treatment goals were explored. Sub-groups(based on Anti-SSB antibody positive/negative) were analyzed. Results: Twenty patients with RHC-confirmed pSS-PAH were included (median age at onset, 54.5 years; median PAH duration, 12 months).PAH was the initial manifestation of pSS in 5 patients(26.3%), and shortness of breath was the most common symptom (17/20,85%). Mean pulmonary arterialpressure (mPAP) was 48(38, 55.75)mmHg, pulmonary vascularresistance (PVR) was 11.23 (6.17,14.69)IU, and mean cardiac index was 2.59(2.04,2.98)L·min(-1)·m(-2) in this group. In addition, right ventricular diameter≤40 mm[P=0.009, HR=5.92, 95%CI(1.55, 22.59)] was predictive factor for achieving the treatment goal. Furthermore, compared with Anti-SSB antibody negative patients, patients with Anti-SSB antibody positive had a higher PVR(IU) [14.1(11.23, 22.63)vs 6.4(6.15, 12.36),P=0.025], a higher mPAP(mmHg)[5(48.5,59)vs 39(32.5,50.75),P=0.013], and a lower cardiac index (L·min(-1)·m(-2)) [2.1(1.6,2.5)vs 2.9(2.56,3.41),P=0.002]. Conclusions: pSS-PAH patients are mainly middle-aged women with the most common symptom shortness of breath. And PAH can be the first manifestation of pSS. More attention should be paid to patients with Anti-La/SSB antibody positive and right ventricular diameter ≤40 mm because of higher mPAP, PVR, worse cardiac function and prognosis.

Rheumatoid arthritis patients treated in trial and real world settings: comparison of randomized trials with registries.

Objective: To investigate whether patients with RA enrolled in randomized controlled trials (RCTs) and observational studies may differ in terms of characteristics that could modify treatment effects, leading to an efficacy-effectiveness gap. Methods: We conducted systematic literature reviews to identify RCTs and observational studies with RA, treated with rituximab, tocilizumab or etanercept. We extracted baseline characteristics and compared the data of RCTs and observational studies using fixed-effects meta-analyses for the RCTs and random-effects meta-analyses for the observational studies. We also assessed whether the baseline characteristics changed over time. Results: Compared with patients enrolled in RCTs, those from observational studies were on average 3.0 years older (P < 0.001), suffered from RA for 3.1 years longer (P < 0.001), had 1.6 more prior disease modifying drugs (P = 0.001), and had a lower DAS-28 (difference -0.6, P < 0.001). CRP and ESR levels were slightly higher in RCTs. The HAQ-Disability Index (HAQ-DI) score was slightly lower in the RCT group. No differences were found in the percentages of included females or RF positivity. Over time, we found a significant decrease of - 0.08 in DAS-28 and a decrease of - 0.04 in HAQ-DI both in patients in RCTs and in patients from registries. Furthermore, ESR and CRP declined over time in RCT patients, but not in patients participating in observational studies. Conclusion: There are substantial systematic differences in patient characteristics between RCTs and registries in RA. The efficacy seen in RCTs may not reflect real-world effectiveness.

Baseline characteristics of infected foot ulcers in patients with diabetes at a tertiary care hospital in Pakistan.

OBJECTIVE:: Studies on diabetic foot ulcers (DFU) involving a representative sample of patients in Pakistan are scarce. This study aimed to determine baseline characteristics of infected DFUs in patients hospitalised at the Pakistan Institute of Medical Sciences Islamabad. METHOD:: In this cross-sectional study, carried out during May 2015 and June 2016, foot ulcer characteristics of patients with DFUs were investigated and documented. From infected DFUs, aerobic bacterial pathogens were isolated, identified and evaluated for antimicrobial susceptibility. RESULTS:: A total of 214 patients were recruited to the study, 62.6% of which were male, 90.2% were aged ≥40 years, 76.2% had type 1 diabetes and 78.5% had poor glycaemic control at time of presentation to hospital. Most patients had grade 3/moderate ulceration (based on the Wagner and International Working Group on the Diabetic Foot/Infectious Diseases Society of America criteria). Over half of the DFUs (57.9%) were of ≤3 months' duration and 70.1% were ≥3 cm2. Of the patients with deep infection grade ulcers, 26.6% underwent amputation, accounting for their prolonged hospital stay (≥20 days). Significant differences were observed between patients with type 1 and type 2 diabetes with DFUs in relation to gender (p≤0.0001), ulcer size (p=0.0421) and duration of hospital stay (p=0.0253). The most significant predictors for lower extremity amputation were osteomyelitis (p=0.0114), retinopathy (p=0.0001) and neuropathy (p=0.0001. Piperacillin/tazobactam was found to be an effective antibiotic against the most commonly isolated Staphylococcus non-aureus (35.48%), Pseudomonas aeruginosa (22.26%), and Staphylococcus aureus (20.96%) species indentified in the DFU infections. CONCLUSION:: The findings of this study may be helpful in the optimal management and appropriate treatment of patients with infected DFUs.

Predicting pre- and post-operative acute kidney injury in elderly patients with coronary artery disease.

Background: Limited evidence exists regarding the clinical baseline characteristics at admission for acute kidney injury (AKI) before and after interventional cardiac procedures (ICP) in elderly patients with coronary artery disease (CAD). Methods: A total of 488 elderly patients were enrolled in this retrospective single-center study conducted from January 2019 to July 2022, and a classification and regression tree (CART) analysis was performed to identify the high-risk population. Results: The AKI incidence was 21.1 % (103/488) in this study, with 27 and 76 individuals developing AKI before and after ICP, respectively. CART analysis revealed that exposure to nephrotoxic drugs and diuretics had the strongest predictive capacities for identifying patients at risk of developing pre-ICP AKI, with the incidence among these high-risk patients ranging from 6.5 % to 13.8 %. Meanwhile, the optimum discriminators for identifying those at high risk of post-ICP AKI were the administration of diuretics, D-value ≤ -860 mL, age >73 years, and administration of nephrotoxic drugs, and the latter model predicted that the AKI incidence among high-risk patients was between 50.0 % and 60.0 %. Conclusions: Elderly patients with CAD exhibited an elevated incidence of AKI. CART models suggested that exposure to nephrotoxic drugs and diuretics, D-value, and age were significantly associated with AKI in the elderly with CAD. Importantly, these baseline characteristics at admission could be utilized to identify elderly patients at high risk of pre- and post-ICP AKI.

Baseline characteristics of the patient population in the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus (SAVOR)-TIMI 53 trial.

BACKGROUND AND AIMS: SAVOR-TIMI 53 was designed to study the effects of the DPP-4 inhibitor saxagliptin on cardiovascular outcomes in high risk type 2 diabetes patients with diverse levels of diabetes control and background anti-diabetic drugs. The goal of this article is to describe the baseline characteristics of this hypothesis driven study. MATERIALS AND METHODS: A total of 16 496 diabetic patients from North America (31.9%), Western Europe (26.0%), Eastern Europe (17.3%), Latin America (16.4%) and Asia (8.3%), with either established cardiovascular disease (78.3%) or with ≥two additional cardiovascular risk factors (21.7%) were randomised to saxagliptin or placebo. Biomarkers of inflammation and insulin resistance were taken at baseline and 2 years later in order to correlate saxagliptin effect on cardiovascular outcome to its effect on inflammation and insulin resistance. RESULTS: Mean [+/-standard deviation (SD)] age was 65.0 (+/-8.6) years, 66.9% were male, body mass index was 31.2 kg/m² (+/-5.6), mean diabetes duration was 11.9 years (+/-8.9) and the mean HbA1c 8.0% (+/-1.4%). HbA1c < 7% was most prevalent among North Americans (30.8%) and least among Asians (15.1%), whereas HbA1c > 9% was 30.7% in Latin America 27.0% in Asia and 15.1% in North America. Diabetic retinopathy was reported in 12.3% of patients, nephropathy in 17.7% and amputation in 2.5%. Diabetic treatments categories were as follows: no medication (5.4%), 1 oral anti-diabetic drug (OAD) (25.0%), ≥2 OAD (27.7%) and/or insulin (40.9%). The prevalence of micro-albuminuria was twice as high among insulin users compared with users of ≥2 OAD. Baseline statin use (78.3% overall) varied by region. CONCLUSION: The SAVOR-TIMI 53 patient population, with differing background diabetes control and anti-diabetic treatment, provides global representation of diabetic patients with established cardiovascular disease or at high risk for cardiovascular disease and is well-positioned to determine the effect of saxagliptin on cardiovascular events.

Explaining temporal trends in annualised relapse rates in placebo groups of randomised controlled trials in relapsing multiple sclerosis: systematic review and meta-regression.

BACKGROUND: Recent studies have shown a decrease in annualised relapse rates (ARRs) in placebo groups of randomised controlled trials (RCTs) in relapsing multiple sclerosis (RMS). METHODS: We conducted a systematic literature search of RCTs in RMS. Data on eligibility criteria and baseline characteristics were extracted and tested for significant trends over time. A meta-regression was conducted to estimate their contribution to the decrease of trial ARRs over time. RESULTS: We identified 56 studies. Patient age at baseline (p < 0.001), mean duration of multiple sclerosis (MS) at baseline (p = 0.048), size of treatment groups (p = 0.003), Oxford Quality Scale scores (p = 0.021), and the number of eligibility criteria (p<0.001) increased significantly, whereas pre-trial ARR (p = 0.001), the time span over which pre-trial ARR was calculated (p < 0.001), and the duration of placebo-controlled follow-up (p = 0.006) decreased significantly over time. In meta-regression of trial placebo ARR, the temporal trend was found to be insignificant, with major factors explaining the variation: pre-trial ARR, the number of years used to calculate pre-trial ARR and study duration. CONCLUSION: The observed decline in trial ARRs may result from decreasing pre-trial ARRs and a shorter time period over which pre-trial ARRs were calculated. Increasing patient age and duration of illness may also contribute.

High-Target Hemodiafiltration Convective Dose Achieved in Most Patients in a 6-Month Intermediary Analysis of the CONVINCE Randomized Controlled Trial.

Introduction: High convection volumes in hemodiafiltration (HDF) result in improved survival; however, it remains unclear whether it is achievable in all patients. Methods: CONVINCE, a randomized controlled trial, randomized patients with end-stage kidney disease 1:1 to high-dose HDF versus high-flux hemodialysis (HD) continuation. We evaluated the proportion of patients achieving high-dose HDF target: convection volume per visit of ≥23 l (range ±1 l) at baseline, month 3, and month 6. We compared baseline characteristics in the following 2 ways: (i) patients on target for all 3 visits versus patients who missed target on ≥1 visits and (ii) patients on target for all 3 visits or missing it once versus patients who missed target on ≥2 visits. Results: A total of 653 patients were randomized to HDF. Their mean age was 62.2 (SD 13.5) years, 36% were female, 81% had fistula vascular access, and 33% had diabetes. Across the 3 visits, 75 patients (11%), 27 patients (4%), and 11 patients (2%) missed the convection volume target once, twice, and thrice, respectively. Apart from diabetes, there were no apparent differences in patient characteristics between patients who always achieved the high-dose target (83%) and those who missed the target either once or more (17%) or twice or more (6%). Conclusion: Achieving high-dose HDF is feasible for nearly all patients in CONVINCE and could be maintained during the 6-month follow-up period. Apart from diabetes, there were no other indications for confounding by indication on multivariable analyses that may explain the potential survival advantage for patients receiving high-dose HDF.

Baseline characteristics of patients enrolled in the EMPACT-MI trial.

AIMS: Empagliflozin has been shown to reduce the risk of adverse cardiovascular outcomes in patients with type 2 diabetes and in those with heart failure. The impact of empagliflozin in post-acute myocardial infarction (AMI) patients is unknown. METHODS AND RESULTS: The Study to Test the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction (EMPACT-MI) trial screened 6610 participants with AMI and randomized 6522 to empagliflozin or placebo in addition to standard of care. The median (interquartile) age was 64 (56-71) years and 75.1% of patients were male. Major comorbidities included hypertension (69.1%), type 2 diabetes (31.7%), prior myocardial infarction (13.0%), and atrial fibrillation (10.9%). The majority (74.3%) of patients presented with an ST-elevation myocardial infarction. Overall, 56.9% of patients had acute signs or symptoms of congestion requiring treatment and 78.3% had left ventricular systolic dysfunction with ejection fraction <45%. Clinical characteristics, including baseline demographics, rates of revascularization, and cardiovascular medications at discharge were largely comparable to recent trials of the post-AMI population. CONCLUSION: The EMPACT-MI trial will establish the benefit and risks of empagliflozin treatment in patients with AMI.

Value of baseline characteristics in the risk prediction of atrial fibrillation.

Introduction: Atrial fibrillation (AF) is prone to heart failure and stroke. Early management can effectively reduce the stroke rate and mortality. Current clinical guidelines screen high-risk individuals based solely on age, while this study aims to explore the possibility of other AF risk predictors. Methods: A total of 18,738 elderly people (aged over 60 years old) in Chinese communities were enrolled in this study. The baseline characteristics were mainly based on the diagnosis results of electrocardiogram (ECG) machine during follow up, accompanied by some auxiliary physical examination basic data. After the analysis of both independent and combined baseline characteristics, AF risk predictors were obtained and prioritized according to the results. Independent characteristics were studied from three aspects: Chi-square test, Mann-Whitney U test and Cox univariate regression analysis. Combined characteristics were studied from two aspects: machine learning models and Cox multivariate regression analysis, and the former was combined with recursive feature elimination method and voting decision. Results: The resulted optimal combination of risk predictors included age, atrial premature beats, atrial flutter, left ventricular hypertrophy, hypertension and heart disease. Conclusion: Patients diagnosed by short-time ECG machines with the occurrence of the above events had a higher probability of AF episodes, who are suggested to be included in the focus of long-term ECG monitoring or increased screening density. The incidence of risk predictors in different age ranges of AF patients suggests differences in age-specific patient management. This can help improve the detection rate of AF, standardize the management of patients, and slow down the progression of AF.

Single-group studies in leading physical therapy journals commonly make inappropriate conclusions regarding treatment effect modifiers. A systematic review.

BACKGROUND: Characteristics that identify patients who respond differently to certain interventions are called treatment effect modifiers. Some studies inappropriately report the presence of treatment effect modifiers without adequate study designs. OBJECTIVES: To evaluate what proportion of single-group studies published in leading physical therapy journals inappropriately report treatment effect modifiers, and to assess whether the proportion varies over time or between journals. METHODS: A systematic review was conducted of studies published in eight leading physical therapy journals since 2000. Eligible studies were single-group studies (e.g., cohort study or secondary analysis of treatment arm of randomised controlled trial) that investigated any condition, treatment or outcome. Studies that suggested participants with certain baseline characteristics responded better/or worse to the treatment, were considered to have reported inappropriately. Studies reporting that participants with certain baseline characteristics had improved outcomes but did not state it was due to the treatment were considered to have reported appropriately. The proportion of inappropriate reporting was compared over time and between journals. RESULTS: Of the 145 included studies, 73 (50.3%) were categorised as inappropriately reporting treatment effect modifiers. The proportion of inappropriate reporting was highest in the most recent period, 2018 - 2022 (59.6%) and 2006 - 2011 (55.6%). The proportion of inappropriate reporting varied substantially between journals from 0% (Journal of Physiotherapy) to 91.7% (Journal of Neurologic Physical Therapy). CONCLUSIONS: A large proportion (50.3%) of single-arm studies in leading physical therapy journals inappropriately report treatment effect modifiers. This inappropriate reporting risks misleading clinicians when selecting interventions for individual patients.

Herpetic Anterior Uveitis Multicentre Longitudinal Study (The UVHER Project). Baseline Characteristics.

PURPOSE: The aim of the UVHER project is to evaluate the risk of development of optic nerve damage in patients with herpetic anterior uveitis (AU) prospectively followed over 2 years. Herein, we described the baseline characteristics. METHODS: This is a multicentre, prospective study. An aqueous humour tap was performed. Only patients with a positive PCR were included. Clinical characteristics, optical coherence tomography (OCT) parameters and visual field (VF) abnormalities were registered. RESULTS: 27 patients were included: 18 Herpes Simplex (HSV), one Varicella Zoster (VVZ), and 8Cytomegalovirus (CMV). Patients with HSV-AU had severe inflammation, iris atrophy and corneal involvement. In patients with CMV-AU, less inflammation and medium-to-large keratic precipitates were observed. OCT showed a thinner RNFL and GCL in CMV-AU patients in comparison to HSV patients. VF showed abnormalities in six cases. CONCLUSIONS: Patients in the UVHER cohort showed the typical clinical manifestations of herpetic AU. In CMV patients, optic nerve damage was observed at baseline, and in HSV patients, inflammation was more severe.

Prevalence and implications of significance testing for baseline covariate imbalance in randomised cancer clinical trials: The Table 1 Fallacy.

BACKGROUND: The 'Table 1 Fallacy' refers to the unsound use of significance testing for comparing the distributions of baseline variables between randomised groups to draw erroneous conclusions about balance or imbalance. We performed a cross-sectional study of the Table 1 Fallacy in phase III oncology trials. METHODS: From ClinicalTrials.gov, 1877 randomised trials were screened. Multivariable logistic regressions evaluated predictors of the Table 1 Fallacy. RESULTS: A total of 765 randomised controlled trials involving 553,405 patients were analysed. The Table 1 Fallacy was observed in 25% of trials (188 of 765), with 3% of comparisons deemed significant (59 of 2353), approximating the typical 5% type I error assertion probability. Application of trial-level multiplicity corrections reduced the rate of significant findings to 0.3% (six of 2345 tests). Factors associated with lower odds of the Table 1 Fallacy included industry sponsorship (adjusted odds ratio [aOR] 0.29, 95% confidence interval [CI] 0.18-0.47; multiplicity-corrected P < 0.0001), larger trial size (≥795 versus <280 patients; aOR 0.32, 95% CI 0.19-0.53; multiplicity-corrected P = 0.0008), and publication in a European versus American journal (aOR 0.06, 95% CI 0.03-0.13; multiplicity-corrected P < 0.0001). CONCLUSIONS: This study highlights the persistence of the Table 1 Fallacy in contemporary oncology randomised controlled trials, with one of every four trials testing for baseline differences after randomisation. Significance testing is a suboptimal method for identifying unsound randomisation procedures and may encourage misleading inferences. Journal-level enforcement is a possible strategy to help mitigate this fallacy.