In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in ...patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban.
Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event death, ischaemic stroke, or myocardial infarction (MI) was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI.
Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. ClinicalTrials.gov Identifier: NCT00412984.
STUDY QUESTION
Does the efficacy of placing a copper intrauterine device (IUD) for emergency contraception (EC) to prevent pregnancy depend on menstrual cycle timing and timing of unprotected ...intercourse (UPI)?
SUMMARY ANSWER
If the urine pregnancy test is negative prior to IUD placement, the copper IUD is highly effective for EC at any point in the menstrual cycle.
WHAT IS KNOWN ALREADY
The use of the Copper T380A for EC has been encouraged by the failure of oral EC methods to decrease rates of unintended pregnancy and the documented success of the IUD in reducing unintended pregnancies. However scant data exist regarding the efficacy and safety of IUD insertion for EC when accounting for menstrual cycle timing and time since UPI.
STUDY DESIGN, SIZE, DURATION
This is a secondary analysis of data obtained from a previously published prospective cohort study of women who received the Copper T380A IUD for EC between July 1997 and January 2000. We included 1840 participants according to the study inclusion criteria of a known last menstrual period (LMP) and cycle lengths of 25–35 days.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The original study included women aged between 18 and 44 years who presented for EC at 18 sites throughout China and who had regular menstrual cycles between 24 and 42 days, a known LMP, UPI within 120 h (5 days) and a negative urine pregnancy test (cutoff <25 IU/ml). Women with uncertain LMP dates were excluded. This study included only participants with cycle lengths of 25–35 days.
MAIN RESULTS AND THE ROLE OF CHANCE
Among the 1840 participants with usual cycle lengths of 25–35 days, 850 (46.2%) had their IUD inserted following UPI in the expected fertile window and 84 (4.6%) had the insertion >5 days after the predicted ovulation day and 52 (2.8%) had the insertion >5 days after UPI. There were no pregnancies in the first month among the 1771 women who had information available regarding their 1-month follow-up pregnancy test.
LIMITATIONS, REASONS FOR CAUTION
This was a secondary analysis of an observational study, and thus participants were not randomized to an alternative postcoital method. There were a small number of women who had UPI >5 days after their predicted ovulation day thus limiting the confidence of assuring a low risk of pregnancy in this situation. The ovulation day was calculated based on the LMP prior to IUD insertion and not on the subsequent first day of menses following IUD insertion.
WIDER IMPLICATIONS OF THE FINDINGS
If the urine pregnancy test is negative prior to IUD placement, the copper IUD is likely to be effective for EC at almost any point in the menstrual cycle.
STUDY FUNDING/COMPETING INTEREST(S)
The original study was funded by the UNDP/UNPFA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction. The donors and sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, writing of the report or the decision to submit the paper for publication.
The authors offer some comments on the advantages and possible drawbacks of using the SLICC criteria in longitudinal observational studies and clinical trials after applying and comparing them to the ...ACR criteria in two multinational, multiethnic lupus cohorts.
Please cite this paper as: Wu S, Godfrey E, Wojdyla D, Dong J, Cong J, Wang C, von Hertzen H. Copper T380A intrauterine device for emergency contraception: a prospective, multicentre, cohort clinical ...trial. BJOG 2010;117:1205–1210.
Objective To determine the effectiveness of the Copper T380A (CuT380A) intrauterine device (IUD) as an emergency contraceptive in women.
Design Prospective, multicentre, cohort clinical trial.
Setting Eighteen family planning clinics in China.
Sample A cohort of 1963 women, aged 18–44 years, requesting emergency contraception within 120 hours of unprotected sexual intercourse.
Methods Women requesting emergency contraception were followed at 1, 3 and 12 months after the insertion of CuT380A.
Main outcome measures Efficacy of CuT380A as emergency contraception and for up to 12 months of postinsertion use. Insertion complication rates, reported side‐effects and continuation rates at 12 months were also recorded.
Results No pregnancies occurred prior to or at the first follow‐up visit, making CuT380A 100% effective as emergency contraception in this study. The pregnancy rate over the 12‐month period was 0.23 per 100 women. In all, 29 (1.5%) women experienced a difficult IUD insertion process, requiring local anaesthesia or prophylactic antibiotics. No uterine perforations occurred. The main side‐effects were increased menstrual bleeding and menstrual disturbances. The 12‐month postinsertion continuation rate was 94.0 per 100 woman‐years.
Conclusions CuT380A is a safe and effective method for emergency contraception. The advantages of CuT380A include its ability to provide effective, long‐term contraception.
Objective
To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with ...SLE.
Methods
Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (<50 and ≥50) using descriptive statistics and hypothesis tests. Logistic regression was performed to examine the association of late-onset lupus, adjusting for other variables.
Results
Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p < 0.002) and a longer time to diagnosis (10.1 vs. 5.8 months, p < 0.001) compared to the younger onset group. Malar rash, photosensitivity, and renal involvement were less prevalent while interstitial lung disease, pleural effusions, and sicca symptoms were more frequent in the older age group (p > 0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR = 3.66, 95% CI = 2.15–6.23), pulmonary (OR = 2.04, 95% CI = 1.01–4.11), and cardiovascular (OR = 1.76, 95% CI = 1.04–2.98) involvement and lower odds of cutaneous involvement (OR = 0.41, 95% CI = 0.21–0.80), number of cumulative SLE criteria (OR = 0.79, 95% CI = 0.64–0.97), use of cyclophosphamide (OR = 0.47, 95% CI = 0.24–0.95), and anti-RNP antibodies (OR = 0.43, 95% CI = 0.20–0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR = 2.61, 95% CI = 1.2–5.6).
Conclusion
Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements.
The need for comprehensive published epidemiologic and clinical data from Latin American systemic lupus erythematosus (SLE) patients motivated the late Dr Alarcón-Segovia and other Latin American ...professionals taking care of these patients to spearhead the creation of the Grupo Latino Americano De Estudio del Lupus (GLADEL) cohort in 1997. This inception cohort recruited a total of 1480 multiethnic (Mestizo, African-Latin American (ALA), Caucasian and other) SLE patients diagnosed within two years from the time of enrollment from 34 Latin American centers with expertise in the diagnosis and management of this disease. In addition to the initial 2004 description of the cohort, GLADEL has contributed to improving our knowledge about the course and outcome of lupus in patients from this part of the Americas. The major findings from this cohort are highlighted in this review. They have had important clinical implications for the adequate care of SLE patients both in Latin America and worldwide where these patients may have emigrated.
Objectives
The objectives of this study were to examine the demographic and clinical features associated with the occurrence of pleuropulmonary manifestations, the predictive factors of their ...occurrence and their impact on mortality in systemic lupus erythematosus (SLE) patients.
Materials and methods
The association of pleuropulmonary manifestations with demographic and clinical features, the predictive factors of their occurrence and their impact on mortality were examined in GLADEL patients by appropriate univariable and multivariable analyses.
Results
At least one pleuropulmonary manifestation occurred in 421 of the 1480 SLE patients (28.4%), pleurisy being the most frequent (24.0%). Age at SLE onset ≥30 years (OR 1.42; 95% CI 1.10–1.83), the presence of lower respiratory tract infection (OR 3.19; 95% CI 2.05–4.96), non-ischemic heart disease (OR 3.17; 95% CI 2.41–4.18), ischemic heart disease (OR 3.39; 95% CI 2.08–5.54), systemic (OR 2.00; 95% CI 1.37–2.91), ocular (OR 1.58; 95% CI 1.16–2.14) and renal manifestations (OR 1.44; 95% CI 1.09–1.83) were associated with pleuropulmonary manifestations, whereas cutaneous manifestations were negatively associated (OR 0.47; 95% CI 0.29–0.76). Non-ischemic heart disease (HR 2.24; 95% CI 1.63–3.09), SDI scores ≥1 (OR 1.54; 95% CI 1.10–2.17) and anti-La antibody positivity (OR 2.51; 95% CI 1.39–4.57) independently predicted their subsequent occurrence. Cutaneous manifestations were protective of the subsequent occurrence of pleuropulmonary manifestations (HR 0.62; 95% CI 0.43–0.90). Pleuropulmonary manifestations independently contributed a decreased survival (HR: 2.79 95% CI 1.80–4.31).
Conclusion
Pleuropulmonary manifestations are frequent in SLE, particularly pleuritis. Older age, respiratory tract infection, cardiac, systemic and renal involvement were associated with them, whereas cutaneous manifestations were negatively associated. Cardiac compromise, SDI scores ≥1 and anti-La positivity at disease onset were predictive of their subsequent occurrence, whereas cutaneous manifestations were protective. They independently contributed to a decreased survival in these patients.
Purpose
The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients.
Methods
A case-control study nested within the Grupo Latino ...Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up.
Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0–25%), occasionally (>25%–50%), commonly (˃50%–75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used.
The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models.
Results
A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869–0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522–0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309–2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005–1.064; p = 0.022).
Conclusions
In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.
Objectives
The objective of this study was to examine whether early discoid lupus erythematosus (DLE) would be a protective factor for further lupus nephritis in patients with systemic lupus ...erythematosus (SLE).
Methods
We studied SLE patients from GLADEL, an inception longitudinal cohort from nine Latin American countries. The main predictor was DLE onset, which was defined as physician-documented DLE at SLE diagnosis. The outcome was time from the diagnosis of SLE to new lupus nephritis. Univariate and multivariate survival analyses were conducted to examine the association of DLE onset with time to lupus nephritis.
Results
Among 845 GLADEL patients, 204 (24.1%) developed lupus nephritis after SLE diagnosis. Of them, 10 (4.9%) had DLE onset, compared to 83 (12.9%) in the group of 641 patients that remained free of lupus nephritis (hazard ratio 0.39; P = 0.0033). The cumulative proportion of lupus nephritis at 1 and 5 years since SLE diagnosis was 6% and 14%, respectively, in the DLE onset group, compared to 14% and 29% in those without DLE (P = 0.0023). DLE onset was independently associated with a lower risk of lupus nephritis, after controlling for sociodemographic factors and disease severity at diagnosis (hazard ratio 0.38; 95% confidence interval 0.20–0.71).
Conclusions
Our data indicate that DLE onset reduces the risk of further lupus nephritis in patients with SLE, independently of other factors such as age, ethnicity, disease activity, and organ damage. These findings have relevant prognosis implications for SLE patients and their clinicians. Further studies are warranted to unravel the biological and environmental pathways associated with the protective role of DLE against renal disease in patients with SLE.
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