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Objectives To analyse the amount, reporting and handling of missing data, approach to intention-to-treat (ITT) principle application and sensitivity analysis utilisation in randomised clinical trials (RCTs) of rheumatoid arthritis (RA). To assess the trend in such reporting 10 years apart (2006 and 2016). Methods Parallel group drug therapy RA RCTs with a clinical primary endpoint. Results 176 studies enrolling a median of 160 (IQR 62–339) patients were eligible. In terms of actual analysis: 81 (46%) RCTs conducted ITT, 42 (23.9%) conducted modified ITT while 53 (30.1%) conducted non-ITT analysis. Only 58 of 97 (59.8%) RCTs reporting an ITT analysis actually performed it. The median (IQR) numbers of participants completing the trial and included in analysis for primary outcome were 86% (74%–91%) and 100% (97.1%–100%), respectively. 53 (32.7%) and 65 (40.1%) RCTs had >20% and 10%–20% missing primary outcome data, respectively. Missing data handling was unreported by 58 of 171 (33.9%) RCTs. When reported, vast majority used simple imputation methods. No significant trend towards improved reporting was seen between 2006 and 2016. Sensitivity analysis numerically improved from 2006 to 2016 (14.7% vs 21.4%). Conclusions There is significant discrepancy in the reported and the actual performed analysis in RA drug therapy RCTs. Nearly one-third of RCTs had >20% missing data. The reporting and methods of missing data handling remain inadequate with high usage of non-preferred simple imputation methods. Sensitivity analysis utilisation was low. No trend towards better missing data reporting and handling was seen.

PURPOSE Among Bruton's tyrosine kinase inhibitors, acalabrutinib has greater selectivity than ibrutinib, which we hypothesized would improve continuous therapy tolerability. We conducted an open-label, randomized, noninferiority, phase III trial comparing acalabrutinib and ibrutinib in patients with chronic lymphocytic leukemia (CLL). METHODS Patients with previously treated CLL with centrally confirmed del(17)(p13.1) or del(11)(q22.3) were randomly assigned to oral acalabrutinib 100 mg twice daily or ibrutinib 420 mg once daily until progression or unacceptable toxicity. The primary end point was independent review committee–assessed noninferiority of progression-free survival (PFS). RESULTS Overall, 533 patients (acalabrutinib, n = 268; ibrutinib, n = 265) were randomly assigned. At the data cutoff, 124 (46.3%) acalabrutinib patients and 109 (41.1%) ibrutinib patients remained on treatment. After a median follow-up of 40.9 months, acalabrutinib was determined to be noninferior to ibrutinib with a median PFS of 38.4 months in both arms (95% CI acalabrutinib, 33.0 to 38.6 and ibrutinib, 33.0 to 41.6; hazard ratio: 1.00; 95% CI, 0.79 to 1.27). All-grade atrial fibrillation/atrial flutter incidence was significantly lower with acalabrutinib versus ibrutinib (9.4% v 16.0%; P = .02); among other selected secondary end points, grade 3 or higher infections (30.8% v 30.0%) and Richter transformations (3.8% v 4.9%) were comparable between groups and median overall survival was not reached in either arm (hazard ratio, 0.82; 95% CI, 0.59 to 1.15), with 63 (23.5%) deaths with acalabrutinib and 73 (27.5%) with ibrutinib. Treatment discontinuations because of adverse events occurred in 14.7% of acalabrutinib-treated patients and 21.3% of ibrutinib-treated patients. CONCLUSION In this first direct comparison of less versus more selective Bruton's tyrosine kinase inhibitors in CLL, acalabrutinib demonstrated noninferior PFS with fewer cardiovascular adverse events.

Background: Atrial fibrillation (AF) is a low-flow state and may underestimate aortic stenosis (AS) severity. Single-high Doppler signals (HS) consistent with severe AS (peak velocity ≥4 m/s or mean gradient ≥40 mm Hg) are averaged down in current practice. The objective for the study was to determine the significance of HS in AF low-gradient AS (LGAS). Methods: One thousand five hundred forty-one patients with aortic valve area ≤1 cm 2 and left ventricular ejection fraction ≥50% were identified and classified as high-gradient AS (HGAS) (≥40 mm Hg) and LGAS (<40 mm Hg), and AF versus sinus rhythm (SR). Available computed tomography aortic valve calcium scores (AVCS) were retrieved from the medical record. Outcomes were assessed. Results: Mean age was 76±11 years, female 47%. Mean gradient was 51±12 in SR-HGAS, 48±10 in AF-HGAS, 31±5 in SR-LGAS, and 29±7 mm Hg in AF-LGAS, all P ≤0.001 versus SR-HGAS; HS were present in 33% of AF-LGAS. AVCS were available in 34%. Compared with SR-HGAS (2409 arbitrary units; interquartile range, 1581–3462) AVCS were higher in AF-HGAS (2991 arbitrary units; IQR1978–4229, P =0.001), not different in AF-LGAS (2399 arbitrary units; IQR1817–2810, P =0.47), and lower in SR-LGAS (1593 arbitrary units; IQR945–1832, P <0.001); AVCS in AF-LGAS were higher when HS were present ( P =0.048). Compared with SR-HGAS, the age-, sex-, comorbidity index-, and time-dependent aortic valve replacement-adjusted mortality risk was higher in AF-HGAS (hazard ratio=1.82 [1.40–2.36], P <0.001) and AF-LGAS with HS (hazard ratio=1.54 [1.04–2.26], P =0.03) but not different in AF-LGAS without HS or SR-LGAS (both P =not significant). Conclusions: Severe AS was common in AF-LGAS. AVCS in AF-LGAS were not different from SR-HGAS. AVCS were higher and mortality worse in AF-LGAS when HS were present.

Waldenström Macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is often differentiated from myeloma based on the presence of lytic bone lesions (LBL). However, WM/LPL can present with LBL and management is poorly understood. We describe a case of an 81-year-old woman with LPL who presented with LBL and was successfully treated with chemoimmunotherapy.

Abstract Background: The current pandemic of COVID-19 impacted the psychological wellbeing of populations globally. Objectives: We aimed to examine the extent and identify associated factors of psychological distress, fear of COVID-19, and coping.Methods: We conducted a cross-sectional study across 17 countries during Jun-2020 to Jan-2021. Levels of psychological distress (Kessler Psychological Distress Scale), fear of COVID-19 (Fear of COVID-19 Scale), and coping (Brief Resilient Coping Scale) were assessed. Results: A total of 8,559 people participated; mean age (±SD) was 33(±13) years, 64% were females and 40% self-identified as frontline workers. More than two-thirds (69%) experienced moderate-to-very high levels of psychological distress, which was 46% in Thailand and 91% in Egypt. A quarter (24%) had high levels of fear of COVID-19, which was as low as 9% in Libya and as high as 38% in Bangladesh. More than half (57%) exhibited medium to high resilient coping; the lowest prevalence (3%) was reported in Australia and the highest (72%) in Syria. Being female (AOR 1.31 [95% CIs 1.09-1.57]), perceived distress due to change of employment status (1.56 [1.29-1.90]), comorbidity with mental health conditions (3.02 [1.20-7.60]) were associated with higher levels of psychological distress and fear. Doctors had higher psychological distress (1.43 [1.04-1.97]), but low levels of fear of COVID-19 (0.55 [0.41-0.76]); nurses had medium to high resilient coping (1.30 [1.03-1.65]). Conclusions: The extent of psychological distress, fear of COVID and coping varied by country; however, some groups were more vulnerable than others. There is an urgent need to prioritise health and well-being of these people through well-designed intervention that may need to be tailored to meet country specific requirements.

BACKGROUND The United States (US)‐Mexico border is a socioeconomically underserved area. We sought to investigate whether stroke‐related mortality varies between the US border and nonborder counties. METHODS AND RESULTS We used death certificates from the Centers for Disease Control and Prevention Wide‐Ranging Online Data for Epidemiologic Research database to examine stroke‐related mortality in border versus nonborder counties in California, Texas, New Mexico, and Arizona. We measured average annual percent changes (AAPCs) in age‐adjusted mortality rates (AAMRs) per 100 000 between 1999 and 2018. Overall, AAMRs were higher for nonborder counties, older adults, men, and non‐Hispanic Black adults than their counterparts. Between 1999 and 2018, AAMRs reduced from 55.8 per 100 000 to 34.4 per 100 000 in the border counties (AAPC, −2.70) and 64.5 per 100 000 to 37.6 per 100 000 in nonborder counties (AAPC, −2.92). The annual percent change in AAMR initially decreased, followed by stagnation in both border and nonborder counties since 2012. The AAPC in AAMR decreased in all 4 states; however, AAMR increased in California’s border counties since 2012 (annual percent change, 3.9). The annual percent change in AAMR decreased for older adults between 1999 and 2012 for the border (−5.10) and nonborder counties (−5.01), followed by a rise in border counties and stalling in nonborder counties. Although the AAPC in AAMR decreased for both sexes, the AAPC in AAMR differed significantly for non‐Hispanic White adults in border (−2.69) and nonborder counties (−2.86). The mortality decreased consistently for all other ethnicities/races in both border and nonborder counties. CONCLUSIONS Stroke‐related mortality varied between the border and nonborder counties. Given the substantial public health implications, targeted interventions aimed at vulnerable populations are required to improve stroke‐related outcomes in the US‐Mexico border area.

Background: Prior ATPIII lipid guidelines recommended statin therapy for patients with clinical ASCVD to achieve low density lipoprotein cholesterol (LDL-C) targets, while the 2013 ACC/AHA lipid guidelines recommend high-intensity statin therapy for all ASCVD patients. How closely these recommendations are followed in routine clinical practice is unknown. Methods: We evaluated statin use, intensity, and LDL-C values in 1,483 patients with ASCVD (coronary heart disease, cerebrovascular disease, and peripheral arterial disease) enrolled and seen serially at 62 geographically dispersed US cardiology and primary care clinics in the Patient and Provider Assessment of Lipid Management (PALM) Registry between May - September 2015. Factors associated with high intensity statin use (atorvastatin ≥40 mg or rosuvastatin ≥20 mg daily) and LDL-C <70 mg/dL were evaluated in multivariable logistic regression. Results: Of 1,483 ASCVD patients, 86.2% were on a statin, but only 31.4% were on a high-intensity statin. Overall, 64.0% had an LDL-C <100 mg/dL, but only 29.0% had an LDL-C <70 mg/dL. Factors associated with high-intensity statin use in multivariable regression were younger age (OR 0.74 per 10 year increase, p<0.001, 95% CI 0.66-0.83), male sex (OR 1.69, p<0.001, 95% CI, 1.32-2.16), cerebrovascular disease (OR 1.55, p=0.008, 95% CI 1.12-2.13), coronary heart disease (OR 2.42, p<0.001, 95% CI 1.67-3.50), and being seen by a cardiologist (OR 1.35, p =0.04, 95% CI 1.01-1.81). Factors associated with an increased likelihood of LDL-C<70 were male sex (OR 1.55, p=0.001, 95% CI 1.20-2.01), white (OR 1.62, p=0.03, 95% CI 1.04-2.5-, diabetes (OR 1.64, p<0.001, 95% CI 1.29-2.09) and being seen by a cardiologist (OR 1.94, p<0.001, 95% CI 1.41-2.67). Discussion: Substantial gaps in care remain for secondary prevention of ASCVD despite simplified recommendations. While the majority of patients with ASCVD in community practice are on a statin, only one-third are on high intensity statins and over two-thirds have LDL ≥70 mg/dL.

Timed Up and Go test predicts one-year mortality among patients cardiovascular events after percutaneous coronary intervention Nadeem A. Khan, R. Jay Widmer, Amrit Kanwar, Mohammed A. Al-Hijji, Abdallah El Sabbagh, Ryan J. Lennon, Rajiv Gulati, Amir Lerman, Arashk Motiei, Mandeep Singh Background: Frailty is frequently seen in older adults and among patients with cardiovascular disease (CVD). Timed Up and Go Test (TUG) is a reliable and validated measure of frailty. We aim to assess 1-year mortality and stratify patients based on the performance on the test. Methods: Patients ≥55 years and referred to the cardiac catheterization laboratory underwent the TUG, a simple test to measure static and dynamic balance. We timed the patients while they were instructed to rise from the chair, walk 3 meters (or 10 feet), turn around, and walk back to the chair and sit down. Timing was divided in four categories [<7 sec (controls), 8-10 sec, 11-14 sec, and > 15 sec]. Mortality at one year was evaluated using a Cox proportional hazards model. Results: Those with TUG >15s were older (75.8 ±9.1years vs. 71.2±9.2 years in controls; P<0.001) and more women (42% vs. 29%) had TUG >15s, P=0.002. Patients with TUG >15 s had a significantly increased risk of mortality on follow-up (HR 3.88, 95% CI 1.97-7.66; P<0.001, Figure) which remained significant after adjusting for age and sex (HR 1.86, 95% CI 1.05, 3.30). Conclusions: The TUG test predicts one year mortality among patients referred to the cardiac catheterization laboratory. These data underscore the importance of frailty assessment in patients with CVD.

Abstract The recommended diagnostic criteria for achalasia have been recently updated by Chicago Classification version 4.0 (CCv4.0), the widely accepted classification scheme for esophageal motility disorders using metrics from high‐resolution manometry (HRM). CCv4.0 continued upon prior versions by subtyping achalasia into type I, type II, and type III on HRM. The achalasia subgroup of the CCv4.0 Working Group developed both conclusive and inconclusive statements for the HRM diagnoses of achalasia subtypes. Conclusive achalasia on HRM is defined as an abnormal median integrated relaxation pressure (IRP) in the primary position of wet swallows along with 100% failed peristalsis, with type I achalasia having 100% failed peristalsis without panesophageal pressurization (PEP), type II achalasia with PEP in at least 20% of swallows, and type III achalasia having at least 20% of swallows premature with no appreciable peristalsis. An inconclusive HRM diagnosis of achalasia can arise when there is an integrated relaxation pressure (IRP) that is borderline or at the upper limit of normal in at least one position, there is an abnormal IRP in both positions but evidence of peristalsis with PEP or premature swallows, or there is peristalsis in the secondary position after apparent achalasia in the primary position. In patients with dysphagia and an inconclusive HRM diagnosis of achalasia, supportive testing beyond HRM such as a timed barium esophagram (TBE) for functional lumen imaging probe (FLIP) is recommended. The review recommends a diagnostic algorithm for achalasia, discusses therapeutic options for the disease, and outlines future needs on this topic.