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Background The follow-up rate, a standard index of the completeness of follow-up, is important for assessing the validity of a cohort study. A common method for estimating the follow-up rate, the “Percentage Method”, defined as the fraction of all enrollees who developed the event of interest or had complete follow-up, can severely underestimate the degree of follow-up. Alternatively, the median follow-up time does not indicate the completeness of follow-up, and the reverse Kaplan-Meier based method and Clark’s Completeness Index (CCI) also have limitations. Methods We propose a new definition for the follow-up rate, the Person-Time Follow-up Rate (PTFR), which is the observed person-time divided by total person-time assuming no dropouts. The PTFR cannot be calculated directly since the event times for dropouts are not observed. Therefore, two estimation methods are proposed: a formal person-time method (FPT) in which the expected total follow-up time is calculated using the event rate estimated from the observed data, and a simplified person-time method (SPT) that avoids estimation of the event rate by assigning full follow-up time to all events. Simulations were conducted to measure the accuracy of each method, and each method was applied to a prostate cancer recurrence study dataset. Results Simulation results showed that the FPT has the highest accuracy overall. In most situations, the computationally simpler SPT and CCI methods are only slightly biased. When applied to a retrospective cohort study of cancer recurrence, the FPT, CCI and SPT showed substantially greater 5-year follow-up than the Percentage Method (92%, 92% and 93% vs 68%). Conclusions The Person-time methods correct a systematic error in the standard Percentage Method for calculating follow-up rates. The easy to use SPT and CCI methods can be used in tandem to obtain an accurate and tight interval for PTFR. However, the FPT is recommended when event rates and dropout rates are high.

ObjectivesExtension of disease beyond the atrioventricular (AV) node is associated with increased mortality in cardiac neonatal lupus (NL). Treatment of isolated heart block with fluorinated steroids to prevent disease progression has been considered but published data are limited and discordant regarding efficacy. This study evaluated whether fluorinated steroids given to manage isolated advanced block prevented development of disease beyond the AV node and conferred a survival benefit.MethodsIn this retrospective study of cases enrolled in the Research Registry for NL, inclusion was restricted to anti-SSA/Ro-exposed cases presenting with isolated advanced heart block in utero who either received fluorinated steroids within 1 week of detection (N=71) or no treatment (N=85). Outcomes evaluated were: development of endocardial fibroelastosis, dilated cardiomyopathy and/or hydrops fetalis; mortality and pacemaker implantation.ResultsIn Cox proportional hazards regression analyses, fluorinated steroids did not significantly prevent development of disease beyond the AV node (adjusted HR=0.90; 95% CI 0.43 to 1.85; p=0.77), reduce mortality (HR=1.63; 95% CI 0.43 to 6.14; p=0.47) or forestall/prevent pacemaker implantation (HR=0.87; 95% CI 0.57 to 1.33; p=0.53). No risk factors for development of disease beyond the AV node were identified.ConclusionsThese data do not provide evidence to support the use of fluorinated steroids to prevent disease progression or death in cases presenting with isolated heart block.

Background Lupus patients are at risk for pregnancy loss, and it has been generally accepted that women with SLE should have low disease activity prior to conception. However, there are conflicting results regarding the effect of pregnancy on SLE flares. This study aims to identify predictors of flares during and after pregnancy in SLE patients with inactive or stable disease activity during the first trimester and to characterize and estimate the frequency of post-partum flares in these patients. Methods SLE patients in the multicenter, prospective PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study were evaluated for flares during and after pregnancy using the SELENA-SLEDAI Flare Index. Flares during pregnancy were assessed in all 384 patients and post-partum flares in 234 patients with study visits 2–6 months post-partum. Logistic regression models were fit to the data to identify independent risk factors for flare. Results During pregnancy, 20.8% of patients had mild/moderate flares and 6.25% had severe. Post-partum, 27.7% of patients had mild/moderate flares and 1.7% had severe. The mild flares rarely required treatment. Younger age, low C4 and higher PGA at baseline were independently associated with higher risk of having at least one mild/moderate or severe flare during pregnancy. Older patients were at decreased risk of flare, as well as those with quiescent disease at baseline. No variables evaluated at baseline or the visit most proximal to delivery was significantly associated with risk of flare post-partum. Medications were not associated with flare during or after pregnancy. Conclusion In patients with inactive or stable mild disease activity at the time of conception, lupus disease flares during and after pregnancy are typically mild and occur at similar rates. Flares during pregnancy are predicted by the patients’ age and clinical and serological activity at baseline.

Background Although hydroxychloroquine (HCQ) is a mainstay of treatment for patients with systemic lupus erythematosus (SLE), ocular toxicity can result from accumulated exposure. As the longevity of patients with SLE improves, data are needed to balance the risk of ocular toxicity and the risk of disease flare, especially in older patients with quiescent disease. Accordingly, this study was initiated to examine the safety of HCQ withdrawal in older SLE patients. Methods Data were obtained by retrospective chart review at three major lupus centers in New York City. Twenty-six patients who discontinued HCQ and thirty-two patients on HCQ matched for gender, race/ethnicity, and age were included in this study. The primary outcome was the occurrence of a lupus flare classified by the revised version of the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare composite index, within 1 year of HCQ withdrawal or matched time of continuation. Results Five patients (19.2%) in the HCQ withdrawal group compared to five (15.6%) in the HCQ continuation group experienced a flare of any severity (odds ratio [OR] = 1.28; 95% CI 0.31, 5.30; p  = 0.73). There were no severe flares in either group. The results were similar after adjusting for length of SLE, number of American College of Rheumatology criteria, low complement levels, and SELENA-SLEDAI score, and in a propensity score analysis (OR = 1.18; 95% CI 0.23, 6.16; p  = 0.84). The analysis of time to any flare revealed a non-significant earlier time to flare in the HCQ withdrawal group (log-rank p  = 0.67). Most flares were in the cutaneous and musculoskeletal systems, but one patient in the continuation group developed pericarditis. The most common reason for HCQ withdrawal was retinal toxicity (42.3%), followed by patient’s preference (34.6%), other confirmed or suspected adverse effects (15.4%), ophthalmologist recommendation for macular degeneration (3.8%), and rheumatologist recommendation for quiescent SLE (3.8%). Conclusions In this retrospective study of older stable patients with SLE on long-term HCQ, withdrawal did not significantly increase the risk of flares.

This 24-week randomized, open-label, noninferiority trial compared oral mycophenolate mofetil with monthly intravenous cyclophosphamide as induction therapy for active lupus nephritis. Mycophenolate mofetil appeared more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis, with a more favorable safety profile. Mycophenolate mofetil appeared to be more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis, with a more favorable safety profile. Intravenous cyclophosphamide has been the standard of care for treating severe lupus glomerulonephritis 1 ; however, its use is limited by potentially severe toxic effects including bone marrow suppression, hemorrhagic cystitis, opportunistic infections, malignant diseases, and premature gonadal failure. 2 Clinical trials of treatment with intermittent intravenous cyclophosphamide combined with corticosteroids show greater long-term renal survival but not overall survival, as compared with treatment with corticosteroids alone. 3 – 6 Furthermore, failure to achieve remission, which is associated with an increased rate of progression to renal failure, is reported in 18 to 57 percent of patients who received cyclophosphamide. 7 – 10 Mycophenolate mofetil, an immunosuppressive . . .

ObjectivesNearly 20% of pregnancies in patients with SLE result in an adverse pregnancy outcome (APO). We previously developed an APO prediction model using logistic regression and data from Predictors of pRegnancy Outcome: bioMarkers In Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus (PROMISSE), a large multicentre study of pregnant women with mild/moderate SLE and/or antiphospholipid antibodies. Our goal was to determine whether machine learning (ML) approaches improve APO prediction and identify other risk factors.MethodsThe PROMISSE data included 41 predictors from 385 subjects; 18.4% had APO (preterm delivery due to placental insufficiency/pre-eclampsia, fetal/neonatal death, fetal growth restriction). Logistic regression with stepwise selection (LR-S), least absolute shrinkage and selection operator (LASSO), random forest (RF), neural network (NN), support vector machines (SVM-RBF), gradient boosting (GB) and SuperLearner (SL) were compared by cross-validated area under the ROC curve (AUC) and calibration.ResultsPreviously identified APO risk factors, antihypertensive medication use, low platelets, SLE disease activity and lupus anticoagulant (LAC), were confirmed as important with each algorithm. LASSO additionally revealed potential interactions between LAC and anticardiolipin IgG, among others. SL performed the best (AUC=0.78), but was statistically indistinguishable from LASSO, SVM-RBF and RF (AUC=0.77 for all). LR-S, NN and GB had worse AUC (0.71–0.74) and calibration scores.ConclusionsWe predicted APO with reasonable accuracy using variables routinely assessed prior to the 12th week of pregnancy. LASSO and some ML methods performed better than a standard logistic regression approach. Substantial improvement in APO prediction will likely be realised, not with increasingly complex algorithms but by the discovery of new biomarkers and APO risk factors.

Purpose: To examine the association of adult height with risk of cancer at different anatomic sites in a cohort of men and women. Methods: The association of self-reported height with subsequent cancer risk was assessed in 288,683 men and 192,514 women enrolled in the National Institutes of Health-AARP Diet and Health Study. After a median follow-up of 10.5 years, incident cancer was diagnosed in 51,139 men and 23,407 women. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for the association of height with cancer risk. Results: After adjustment for covariates, height was positively associated with increased risk of all cancers combined in both men [HR10 cm increase = 1.05 (95 % CI 1.04–1.06)] and women [HR10 cm increase = 1.08 (95 % CI 1.06–1.10)]. Several sites common to men and women showed significant positive associations with height: colon, rectum, kidney, melanoma, and non-Hodgkin's lymphoma. For other shared sites, the association differed by sex. For still other sites, there was no clear association with height. Positive associations were also observed with cancers of the breast, endometrium, and prostate. Conclusions: Different patterns were observed in the height–cancer association by sex. Studies investigating the biological mechanisms underlying the association of height with cancer risk should focus on those sites that show a reproducible association with attained height.

The NIH’s Clinical and Translational Science Award (CTSA) program has placed greater emphasis on Continuous Quality Improvement (CQI) in recent years. Our institution’s CTSA-supported Institute for Clinical and Translational Research (ICTR) implemented a novel CQI process in response. This manuscript shares lessons learned from our implementation, reflecting a paradigm shift from managing an “evaluation program” to creating a process whose central goal is CQI. Our objective is to share these reflections to support other CTSA hubs’ efforts to successfully implement CQI programs. Key elements of our implementation included (1) establishing a shared understanding about CQI’s purpose; (2) leveraging a centralized management approach while addressing barriers to implementation; and (3) creating structures that foster collaboration. The CQI framework we chose, FACE (Focus, Analyze, Change, Evaluate), enabled us not only to improve the activities of ICTR modules but also, over time, to refine the CQI process itself. Through regular convenings of module leaders, the ICTR has sought to cultivate a culture of CQI as a dynamic, participatory process that supports mutual learning and collective problem-solving.

ObjectiveThere is a lack of data on the use of telemedicine (TM) in SLE. SLE outcome measures remain complex, and clinicians and clinical trialists have raised concerns about the accuracy of virtual disease activity measures. This study evaluates the level of agreement between virtual SLE outcome measures and face-to-face (F2F) encounter. Here, we describe the study design, virtual physical examination protocol and demographics for the first 50 patients evaluated.Methods and analysisThis is an observational, longitudinal study of 200 patients with SLE with varying levels of disease activity from 4 academic lupus centres serving diverse populations. Each study participant will be evaluated at a baseline and a follow-up visit. At each visit, participants are evaluated by the same physician first via a videoconference-based TM and then a F2F encounter. For this protocol, virtual physical examination guidelines relying on physician-directed patient self-examination were established. SLE disease activity measures will be completed immediately after the TM encounter and repeated after the F2F encounter for each visit. The degree of agreement between TM and F2F disease activity measures will be analysed using the Bland-Altman method. An interim analysis is planned after the enrolment of the first 50 participants.Ethics and disseminationThis study has been reviewed by the Columbia University Medical Center Institutional Review Board (IRB Protocol #: AAAT6574). The full results of this study will be published after the final data analysis of 200 patients. The abrupt shift to TM visits due to the COVID-19 pandemic disrupted clinical practice and clinical trials. Establishing a high level of agreement between SLE disease activity measures obtained with videoconference TM and F2F at the same time point, will allow for improved assessment of disease activity when F2F data cannot be acquired. This information may guide both medical decision-making and provide reliable outcome measures for clinical research.

Purpose: To investigate the association of reproductive factors and hormone therapy, including type of hormone therapy, with risk of thyroid cancer in postmenopausal women. Methods: We assessed these associations with risk of incident thyroid cancer in a cohort of 145,007 postmenopausal women enrolled in the Women's Health Initiative. Over 12.7 years of follow-up, 296 cases of thyroid cancer were identified, including 243 with papillary thyroid cancer. Cox proportional hazards models were used to estimate hazard ratios and 95 % confidence intervals for exposures of interest. Results: In both age-adjusted and multivariable-adjusted analyses, menstrual and reproductive factors including age at menarche, age at menopause, age at first birth, age at last live birth, parity, duration of breastfeeding, miscarriages, stillbirths, hysterectomy, bilateral oophorectomy, and use of oral contraceptives were not associated with risk of all thyroid cancer or papillary thyroid cancer. In addition, ever use of menopausal hormone therapy, current or former use, duration of use, and type were not associated with risk. Conclusion: We found little support for associations of reproductive or hormonal factors with risk of developing thyroid cancer. Importantly, our study showed no association of type of hormone therapy used with thyroid cancer risk.