To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those ...that appeared later.
In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10 years.
53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10 years was 90.7%.
Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.
Objective
This individual patient data (IPD) meta‐analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function ...(SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention‐related characteristics.
Methods
Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed‐effect model analyses were used to study intervention effects on the post‐intervention values of QoL, EF, and SF (z‐scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention‐related characteristics, and conducted subsequent stratified analyses for significant moderator variables.Results: PSI significantly improved QoL (β = 0.14,95%CI = 0.06;0.21), EF (β = 0.13,95%CI = 0.05;0.20), and SF (β = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types.
Conclusions
PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention‐related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.
To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related ...moderators of these effects.
Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics.
For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = −0.09, 95% CI −0.16; −0.02). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances.
This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.
•The exercise interventions can reduce sleep disturbances in patients with cancer•There is no significant improvement of sleep quality after an exercise intervention.•The demographic, clinical, or intervention-related factors were not found to significantly moderate the effect of exercise on sleep.
Objectives
To determine the prevalence, recognition, co‐occurrence, and recent onset of geriatric syndromes in individuals transferred from the hospital to a skilled nursing facility (SNF).
Design
...Quality improvement project.
Setting
Acute care academic medical center and 23 regional partner SNFs.
Participants
Medicare beneficiaries hospitalized between January 2013 and April 2014 and referred to SNFs (N = 686).
Measurements
Project staff measured nine geriatric syndromes: weight loss, lack of appetite, incontinence, and pain (standardized interview); depression (Geriatric Depression Scale); delirium (Brief Confusion Assessment Method); cognitive impairment (Brief Interview for Mental Status); and falls and pressure ulcers (hospital medical record using hospital‐implemented screening tools). Estimated prevalence, new‐onset prevalence, and common coexisting clusters were determined. The extent to which treating physicians commonly recognized syndromes and communicated them to SNFs in hospital discharge documentation was evaluated.
Results
Geriatric syndromes were prevalent in more than 90% of hospitalized adults referred to SNFs; 55% met criteria for three or more coexisting syndromes. The most‐prevalent syndromes were falls (39%), incontinence (39%), loss of appetite (37%), and weight loss (33%). In individuals who met criteria for three or more syndromes, the most common triad clusters were nutritional syndromes (weight loss, loss of appetite), incontinence, and depression. Treating hospital physicians commonly did not recognize and document geriatric syndromes in discharge summaries, missing 33% to 95% of syndromes present according to research personnel.
Conclusion
Geriatric syndromes in hospitalized older adults transferred to SNFs are prevalent and commonly coexist, with the most frequent clusters including nutritional syndromes, depression, and incontinence. Despite the high prevalence, this clinical information is rarely communicated to SNFs on discharge.
Aims
Misclassification of diabetes is common due to an overlap in the clinical features of type 1 and type 2 diabetes. Combined diagnostic models incorporating clinical and biomarker information have ...recently been developed that can aid classification, but they have not been validated using pancreatic pathology. We evaluated a clinical diagnostic model against histologically defined type 1 diabetes.
Methods
We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (n = 111) or non‐type 1 (n = 42) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin‐containing islets along with multiple insulin‐deficient islets. We assessed the discriminative performance of previously described type 1 diabetes diagnostic models, based on clinical features (age at diagnosis, BMI) and biomarker data autoantibodies, type 1 diabetes genetic risk score (T1D‐GRS), and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC‐ROC).
Results
Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D‐GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC‐ROC 0.97 vs. 0.95; P = 0.03). Histological classification of type 1 diabetes was concordant with serum C‐peptide median < 17 pmol/l (limit of detection) vs. 1037 pmol/l in non‐type 1 diabetes; P < 0.0001.
Conclusions
Our study provides robust histological evidence that a clinical diagnostic model, combining clinical features and biomarkers, could improve diabetes classification. Our study also provides reassurance that a C‐peptide‐based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible.
Parts of this study were presented in form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19–22 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6–8 March 2019.
What’s new?
Misclassification of diabetes at diagnosis is common due to an overlap in the clinical features of type 1 and type 2 diabetes.
Combining clinical features and biomarkers in a diagnostic model improved discrimination of diabetes type, defined by insulin deficiency (measured by C‐peptide assays), over use of any single characteristic.
No diabetes classification studies have used pancreatic histology to define type 1 diabetes.
A diagnostic model, developed using diabetes type defined by C‐peptide level as an outcome, validates against histologically defined insulin deficiency.
C‐peptide provides a robust surrogate definition of type 1 diabetes that can be used in diagnostic model development.
Our study provides the first histological evidence for a clinical diagnostic model having utility to identify type 1 diabetes in clinical practice.
Background and purpose
Atrial fibrillation (AF) increases the risk of stroke fourfold and is associated with a poor clinical outcome. Despite work‐up in compliance with guidelines, up to one‐third of ...patients have cryptogenic stroke (CS). The prevalence of asymptomatic paroxysmal atrial fibrillation (PAF) in CS remains unknown. The SURPRISE project aimed at determining this rate using long‐term cardiac monitoring.
Methods
Patients with CS after protocolled work‐up including electrocardiography (ECG) and telemetry were included after informed consent. An implantable loop recorder (ILR) was implanted subcutaneously. PAF was defined by events of atrial arrhythmia >2 min with a correlating one‐lead ECG confirming the diagnosis.
Results
Eighty‐five patients were monitored for a mean of 569 days (SD ±310). PAF was documented in 18 patients (20.7%) during the study period and detected by ILR in 14 patients (16.1%). In three patients PAF was detected by other methods before or after monitoring and was undiscovered due to device sensitivity in one case. The first event of PAF was documented at a mean of 109 days (SD ±48) after stroke onset. PAF was asymptomatic in all cases and occurred in episodes lasting predominantly between 1 and 4 h. Four recurrent strokes were observed, three in patients with PAF; all three patients were on oral anticoagulation (OAC).
Conclusions
One in five patients with CS had PAF, which occurred at low burden and long after stroke. Future studies should determine the role of implantable cardiac monitors after stroke and determine the potential therapeutic benefit of OAC treatment of patients with PAF.
To identify the main causes of morbidity and mortality in patients with antiphospholipid syndrome (APS) during a 5-year period and to determine clinical and immunological parameters with prognostic ...significance.
The clinical and immunological features of a cohort of 1000 patients with APS from 13 European countries who had been followed up from 1999 to 2004 were analysed.
200 (20%) patients developed APS-related manifestations during the 5-year study period. Recurrent thrombotic events appeared in 166 (16.6%) patients and the most common were strokes (2.4% of the total cohort), transient ischaemic attacks (2.3%), deep vein thromboses (2.1%) and pulmonary embolism (2.1%). When the thrombotic events occurred, 90 patients were receiving oral anticoagulants and 49 were using aspirin. 31/420 (7.4%) patients receiving oral anticoagulants presented with haemorrhage. 3/121 (2.5%) women with only obstetric APS manifestations at the start of the study developed a new thrombotic event. A total of 77 women (9.4% of the female patients) had one or more pregnancies and 63 (81.8% of pregnant patients) had one or more live births. The most common fetal complications were early pregnancy loss (17.1% of pregnancies) and premature birth (35% of live births). 53 (5.3% of the total cohort) patients died. The most common causes of death were bacterial infection (21% of deaths), myocardial infarction (19%) and stroke (13%). No clinical or immunological predictor of thrombotic events, pregnancy morbidity or mortality was detected.
Patients with APS still develop significant morbidity and mortality despite current treatment (oral anticoagulants or antiaggregants, or both).
Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disorder caused by an expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene Huntington's Disease ...Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell, 72, 971–983. Despite identification of the gene in 1993, the underlying life-long disease process and effective treatments to prevent or delay it remain elusive. In an effort to fast-track treatment strategies for HD into clinical trials, we have developed a new large-animal HD transgenic ovine model. Sheep, Ovis aries L., were selected because the developmental pattern of the ovine basal ganglia and cortex (the regions primarily affected in HD) is similar to the analogous regions of the human brain. Microinjection of a full-length human HTT cDNA containing 73 polyglutamine repeats under the control of the human promotor resulted in six transgenic founders varying in copy number of the transgene. Analysis of offspring (at 1 and 7 months of age) from one of the founders showed robust expression of the full-length human HTT protein in both CNS and non-CNS tissue. Further, preliminary immunohistochemical analysis demonstrated the organization of the caudate nucleus and putamen and revealed decreased expression of medium size spiny neuron marker DARPP-32 at 7 months of age. It is anticipated that this novel transgenic animal will represent a practical model for drug/clinical trials and surgical interventions especially aimed at delaying or preventing HD initiation. New sequence accession number for ovine HTT mRNA: FJ457100.
Environmental water quality monitoring aims to provide the data required for safeguarding the environment against adverse biological effects from multiple chemical contamination arising from ...anthropogenic diffuse emissions and point sources. Here, we integrate the experience of the international EU-funded project SOLUTIONS to shift the focus of water monitoring from a few legacy chemicals to complex chemical mixtures, and to identify relevant drivers of toxic effects. Monitoring serves a range of purposes, from control of chemical and ecological status compliance to safeguarding specific water uses, such as drinking water abstraction. Various water sampling techniques, chemical target, suspect and non-target analyses as well as an array of in vitro, in vivo and in situ bioanalytical methods were advanced to improve monitoring of water contamination. Major improvements for broader applicability include tailored sampling techniques, screening and identification techniques for a broader and more diverse set of chemicals, higher detection sensitivity, standardized protocols for chemical, toxicological, and ecological assessments combined with systematic evidence evaluation techniques. No single method or combination of methods is able to meet all divergent monitoring purposes. Current monitoring approaches tend to emphasize either targeted exposure or effect detection. Here, we argue that, irrespective of the specific purpose, assessment of monitoring results would benefit substantially from obtaining and linking information on the occurrence of both chemicals and potentially adverse biological effects. In this paper, we specify the information required to: (1) identify relevant contaminants, (2) assess the impact of contamination in aquatic ecosystems, or (3) quantify cause–effect relationships between contaminants and adverse effects. Specific strategies to link chemical and bioanalytical information are outlined for each of these distinct goals. These strategies have been developed and explored using case studies in the Danube and Rhine river basins as well as for rivers of the Iberian Peninsula. Current water quality assessment suffers from biases resulting from differences in approaches and associated uncertainty analyses. While exposure approaches tend to ignore data gaps (i.e., missing contaminants), effect-based approaches penalize data gaps with increased uncertainty factors. This integrated work suggests systematic ways to deal with mixture exposures and combined effects in a more balanced way, and thus provides guidance for future tailored environmental monitoring.
This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects.
Overall effects and ...intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs.
CST had a statistically significant but small effect on depression (g = −0.31,95% confidence interval (CI) = −0.40;-0.22) and anxiety (g = −0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (β = −0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (β = −0.16,95%CI = -0.25;-0.07) and anxiety (β = −0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05).
CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.
•The average effect of CST on symptoms of anxiety and depression in cancer patients are statistically significant but small•Younger patients and patients who received chemotherapy benefit more from CST•CST effects are larger when delivered face-to-face, led by a psychologist and targeted to patients with psychological distress
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