•31.5% patients with suicidal thoughts or behaviors recurred in 1-year follow-up.•Around 70% % of recurrences occurred in the first 6 months.•Seeking psychiatric help for non-STB reasons was a common ...predictor for all STB.•Previous attempts and hospitalization after index episode predicted re-attempts.•Suicidal ideation at the index predicted recurrence in the form of suicidal ideation.
Suicidal thoughts and behaviors (STB) include suicidal ideation (SI), suicide attempt (SA) and completed suicide. We aimed to identify recurrence predictors of any type of STB, and separately for SA and SI, and to analyze the time until event. A 108-subject cohort presenting at Emergencies with STB was followed during one year. Recurrence risk factors were investigated by multiple Cox survival regressions. Within one year, 31.5%, 23.1% and 9.3% patients recurred with any STB, SA, and SI respectively. Most recurrences (~70%) occurred within the first 6 months. Seeking emergency psychiatric assistance for problems other than STB during follow-up was a common predictor for recurrence of any STB, and SA and SI specifically. Previous SA history and contact with psychiatry outpatient units during follow-up predicted both STB in general and SA in particular. A specific predictor for SA was hospitalization at index, while SI recurrence was associated to SI at index. These results highlight the importance of early intervention and multidisciplinary follow-up considering concurrent psychosocial or adaptive problems. A careful exploration at Emergencies is needed to target potential predictors.
Aims
Little is known about the prognosis of patients with massive pulmonary embolism (PE) and its risk of recurrent venous thromboembolism (VTE) compared with non‐massive PE, which may inform ...clinical decisions. Our aim was to compare the risk of recurrent VTE, bleeding, and mortality after massive and non‐massive PE during anticoagulation and after its discontinuation.
Methods and results
We included all participants in the RIETE registry who suffered a symptomatic, objectively confirmed segmental or more central PE. Massive PE was defined by a systolic hypotension at clinical presentation (<90 mm Hg). We compared the risks of recurrent VTE, major bleeding, and mortality using time‐to‐event multivariable competing risk modeling. There were 3.5% of massive PE among 38 996 patients with PE. During the anticoagulation period, massive PE was associated with a greater risk of major bleeding (subhazard ratio sHR 1.72, 95% confidence interval CI 1.28–2.32), but not of recurrent VTE (sHR 1.15, 95% CI 0.75–1.74) than non‐massive PE. An increased risk of mortality was only observed in the first month after PE. After discontinuation of anticoagulation, among 11 579 patients, massive PE and non‐massive PE had similar risks of mortality, bleeding, and recurrent VTE (sHR 0.85, 95% CI 0.51–1.40), but with different case fatality of recurrent PE (11.1% versus 2.4%, P = .03) and possibly different risk of recurrent fatal PE (sHR 3.65, 95% CI 0.82–16.24).
Conclusion
In this large prospective registry, the baseline hemodynamic status of the incident PE did not influence the risk of recurrent VTE, during and after the anticoagulation periods, but was possibly associated with recurrent PE of greater severity.
Recent reports of patients with coronavirus disease 2019 (COVID-19) developing pneumothorax correspond mainly to case reports describing mechanically ventilated patients. The real incidence, clinical ...characteristics, and outcome of spontaneous pneumothorax (SP) as a form of COVID-19 presentation remain to be defined.
Do the incidence, risk factors, clinical characteristics, and outcomes of SP in patients with COVID-19 attending EDs differ compared with COVID-19 patients without SP and non-COVID-19 patients with SP?
This case-control study retrospectively reviewed all patients with COVID-19 diagnosed with SP (case group) in 61 Spanish EDs (20% of Spanish EDs) and compared them with two control groups: COVID-19 patients without SP and non-COVID-19 patients with SP. The relative frequencies of SP were estimated in COVID-19 and non-COVID-19 patients in the ED, and annual standardized incidences were estimated for both populations. Comparisons between case subjects and control subjects included 52 clinical, analytical, and radiologic characteristics and four outcomes.
We identified 40 occurrences of SP in 71,904 patients with COVID-19 attending EDs (0.56‰; 95% CI, 0.40‰-0.76‰). This relative frequency was higher than that among non-COVID-19 patients (387 of 1,358,134, 0.28‰; 95% CI, 0.26‰-0.32‰; OR, 1.93; 95% CI, 1.41-2.71). The standardized incidence of SP was also higher in patients with COVID-19 (34.2 vs 8.2/100,000/year; OR, 4.19; 95% CI, 3.64-4.81). Compared with COVID-19 patients without SP, COVID-19 patients developing SP more frequently had dyspnea and chest pain, low pulse oximetry readings, tachypnea, and increased leukocyte count. Compared with non-COVID-19 patients with SP, case subjects differed in 19 clinical variables, the most prominent being a higher frequency of dysgeusia/anosmia, headache, diarrhea, fever, and lymphopenia (all with OR > 10). All the outcomes measured, including in-hospital death, were worse in case subjects than in both control groups.
SP as a form of COVID-19 presentation at the ED is unusual (< 1‰ cases) but is more frequent than in the non-COVID-19 population and could be associated with worse outcomes than SP in non-COVID-19 patients and COVID-19 patients without SP.
In the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), ...human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness of olaparib in similar patients, in a setting reflecting clinical practice.
This open-label, single-arm trial of olaparib (300 mg, twice daily) enrolled patients with BRCAm, HER2-negative mBC who had received taxane and/or anthracycline in the (neo)adjuvant/metastatic setting and not more than two lines of prior chemotherapy for mBC. Patients with hormone receptor–positive mBC had progressed on at least one line of endocrine therapy in an adjuvant/metastatic setting and were unsuitable for further endocrine treatment. This interim analysis was planned after 160 PFS events.
Of 563 patients screened, 252 patients with gBRCAm were enrolled and received at least one dose of olaparib. The median investigator-assessed PFS was 8.11 months (95% confidence interval CI, 6.93–8.67; 166/252 events 65.9% maturity). The investigator-assessed clinical response rate was 48.6%, and median time to first subsequent treatment or death was 9.66 months (95% CI, 8.67–11.14). The most common treatment-emergent adverse events (TEAEs; >20% patients) were nausea, anaemia, asthenia, vomiting and fatigue. Eleven patients (4.4%) discontinued treatment because of a TEAE. Grade 3 or higher TEAEs occurred in 64 patients (25.4%), including anaemia (33 patients; 13.1%).
Olaparib was clinically effective in patients with gBRCAm, HER2-negative mBC with safety outcomes consistent with previous findings. ClinicalTrials.gov identifier: NCT03286842.
•LUCY was a phase IIIb trial of the PARP inhibitor olaparib.•LUCY followed the phase III OlympiAD trial and aimed to reflect clinical practice.•Investigator-assessed progression-free survival was 8.11 months (65.9% maturity).•Grade ≥3 TEAEs occurred in 64 patients (25.4%), including anaemia in 33 patients.•These interim results support previous findings from the OlympiAD trial.
Objective
Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups ...defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis.
Methods
Unsupervised clustering of integrated whole blood transcriptome and methylome cross‐sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time.
Results
Four clusters were identified and validated. Three were pathologic, representing “inflammatory,” “lymphoid,” and “interferon” patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse–remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient.
Conclusion
Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.
Aims. Using the CoRoT space based photometry of the O-type binary HD 46149, stellar atmospheric effects related to rotation can be separated from pulsations, because they leave distinct signatures in ...the light curve. This offers the possibility of characterising and exploiting any pulsations seismologically. Methods. Combining high-quality space based photometry, multi-wavelength photometry, spectroscopy and constraints imposed by binarity and cluster membership, the detected pulsations in HD 46149 are analyzed and compared with those for a grid of stellar evolutionary models in a proof-of-concept approach. Results. We present evidence of solar-like oscillations in a massive O-type star, and show that the observed frequency range and spacings are compatible with theoretical predictions. Thus, we unlock and confirm the strong potential of this seismically unexplored region in the HR diagram.
Macitentan is a dual endothelin receptor antagonist indicated for the long-term treatment of pulmonary arterial hypertension (PAH). We evaluated the change over time in REVEAL risk score in incident ...and prevalent patients receiving macitentan for the first time.
Retrospective, observational study including adult patients with idiopathic/heritable PAH or PAH associated with connective tissue disorders or congenital heart disease treated with macitentan for ≥6-month follow-up in Spain. The REVEAL risk score and risk strata were computed at the start of macitentan and after ≥6-month in patients with ≥7 out of 12 valid REVEAL components.
Overall, 81 patients (57 for the REVEAL score) were analysed, 77.8% women. The mean age was 57.2 years and 50.6% of patients had idiopathic/heritable PAH. Prevalent patients were 59.3 and 40.7% were incident. Main therapies for PAH included macitentan monotherapy (42.0%) and macitentan in combination with phosphodiesterase type 5 inhibitor (44.4%). With a median time of macitentan treatment of 10.5 months, the mean REVEAL score was 8.7 points at baseline and was 7.2 points after ≥6-month follow-up. The mean change (95% CI) in REVEAL risk score was - 1.4 (- 2.0, - 0.9) points (p < 0.0001), being - 1.8 (- 3.0, - 0.7) points (p = 0.0040) and - 1.2 (- 1.8, - 0.5) points (p = 0.0010), in incident and prevalent patients, respectively. The reduction was also significant by risk stratum (36.8% of patients in the high-very high risk strata at baseline versus 14.0% after ≥6-month, p < 0.05) and therapy group. The REVEAL components that significantly improved were WHO functional class (FC) (63.9% FC III at macitentan initiation and 23.6% after ≥6-month, p < 0.0001), 6-min walk test (mean change: 41.8 m, p < 0.01), brain natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) (mean change of - 157.6 pg/mL and - 530.0 pg/mL, respectively, p < 0.05 both), and pulmonary vascular resistance (PVR) (mean change: - 3.4 WU, p < 0.01).
In this study, treatment with macitentan improved the REVEAL risk strata and score in both incident and prevalent PAH patients, and in all patients regardless of the therapy strategy. Macitentan significantly improved some of REVEAL components including WHO FC, BNP/NT-proBNP, PVR, and 6-min walk test after at least 6-month follow-up.
•We have been able to collect demographic, genetic and clinical data of a large series of patients with Pompe disease in Spain.•The estimated prevalence of Pompe disease in Spain is lower than ...expected and could around 3.1 cases per every millions of habitants.•The region with a higher prevalence of cases is Andalucia, located in the South of Spain.•Our data shows a huge variability in how the diagnosis is obtained and the follow-up is performed across different medical centers in Spain, suggesting that new guidelines are required.
Pompe disease is a rare genetic disorder with an estimated prevalence of 1:60.000. The two main phenotypes are Infantile Onset Pompe Disease (IOPD) and Late Onset Pompe Disease (LOPD). There is no published data from Spain regarding the existing number of cases, regional distribution, clinical features or, access and response to the treatment. We created a registry to collect all these data from patients with Pompe in Spain. Here, we report the data of the 122 patients registered including nine IOPD and 113 LOPD patients. There was a high variability in how the diagnosis was obtained and how the follow-up was performed among different centres. Seven IOPD patients were still alive being all treated with enzymatic replacement therapy (ERT) at last visit. Ninety four of the 113 LOPD patients had muscle weakness of which 81 were receiving ERT. We observed a progressive decline in the results of muscle function tests during follow-up. Overall, the Spanish Pompe Registry is a valuable resource for understanding the demographics, patient's journey and clinical characteristics of patients in Spain. Our data supports the development of agreed guidelines to ensure that the care provided to the patients is standardized across the country.
About 1% of children and adolescents worldwide are affected by plaque psoriasis.
To evaluate the long-term efficacy and safety of ixekizumab for pediatric patients with moderate to severe psoriasis.
...This multicenter randomized clinical trial (IXORA-PEDS) evaluated pediatric patients with plaque psoriasis. Participants were aged 6 years to younger than 18 years; had moderate to severe psoriasis, which was defined as Psoriasis Area and Severity Index (PASI) of 12 or higher, static Physician's Global Assessment (sPGA) score of 3 or higher, and psoriasis-affected body surface area of 10% or greater at screening and baseline; were candidates for phototherapy or systemic therapy; or had psoriasis that was not adequately controlled by topical therapies. Data analysis, which followed the intention-to-treat principle, was conducted from May to October 2021.
Pediatric patients were randomized 2:1 to receive either a weight-based dose of ixekizumab every 4 weeks or placebo. After a 12-week placebo-controlled period, patients entered a 48-week, open-label ixekizumab maintenance period (weeks 12-60), followed by an extension period that lasted through 108 weeks. A substudy evaluated the randomized withdrawal of ixekizumab after week 60.
Efficacy outcomes at week 108 included the percentage of patients achieving 75% (PASI 75), 90% (PASI 90), or 100% (PASI 100) improvement from baseline; an sPGA score of 0 or 1 or score of 0; and improvement of 4 points or higher from baseline in the Itch Numeric Rating Scale. Safety outcomes included assessments of adverse events (AEs), including treatment-emergent AEs, serious AEs, and AEs of special interest, as well as improvement from baseline in a range of challenging body areas. Missing data for categorical outcomes were imputed using modified nonresponder imputation.
A total of 171 patients (mean SD age, 13.5 3.04 years; 99 female children 57.9%) were randomized to either ixekizumab (n = 115) or placebo (n = 56). Of 166 patients who entered the maintenance period, 139 (83.7%) completed week 108 of the trial. Primary and gated secondary end points were sustained through week 108, with patients achieving PASI 75 (91.7% n = 86), PASI 90 (79.0% n = 74), PASI 100 (55.1% n = 52), sPGA 0 or 1 (78.3% n = 74), and sPGA 0 (52.4% n = 49). Fifty-five patients (78.5%) reported an Itch Numeric Rating Scale improvement of 4 points or higher. In patients who received ixekizumab, at week 108, clearance of nail psoriasis was reported in 68.1% (n = 28), clearance of palmoplantar psoriasis was reported in 90.0% (n = 10), clearance of scalp psoriasis was reported in 76.2% (n = 83), and clearance of genital psoriasis was reported in 87.5% (n = 24). There were no new safety findings during weeks 48 to 108 of the trial, including no new cases of inflammatory bowel disease or candida infection.
Results of this study showed improvements across patient-reported outcomes and objective measures of complete skin clearance of psoriasis among pediatric patients who received ixekizumab, and these response rates were sustained through week 108 of the trial. Safety of ixekizumab was consistent with previously reported findings in this population and the known safety profile of this treatment.
ClinicalTrials.gov Identifier: NCT03073200.
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