The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic ...attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.
Patients who present to the hospital for infectious complications of intravenous opioid use are at high risk for against-medical-advice discharge and readmissions. The role of medication-assisted ...treatment for inpatients is not clear. We aimed to assess outcomes prior to and after rollout of an inpatient buprenorphine-based opioid use disorder protocol, as well as to assess outcomes in general for medication-assisted therapy.
This was a retrospective observational cohort study at our community hospital in New Hampshire. The medical record was searched for inpatients with a complication of intravenous opioid use. We searched for admissions 11 months prior to and after the November 2018 buprenorphine protocol rollout.
Rates of medication-assisted therapy usage and buprenorphine linkage increased significantly after protocol rollout. Rates of against-medical-advice discharge did not decrease after protocol rollout, nor did readmissions. However, when evaluating the entire group of patients regardless of date of presentation or protocol use, against-medical-advice discharge rates were substantially lower for patients receiving medication-assisted therapy compared with those receiving supportive care only (30.0% vs 59.6%). Readmissions rates were lower for patients who were discharged with any form of ongoing medication-assisted therapy compared with those who were not (30-day all-cause readmissions 18.8% vs 35.1%; 30-day opioid-related readmissions 10.1% vs 29.9%; 90-day all-cause readmissions 27.3% vs 42.7%; 90-day opioid-related readmissions 15.1% vs 33.3%).
There is a strong association between medication-assisted therapy and reduced against-medical-advice discharge rates. Additionally, maintenance medication-assisted therapy at time of discharge is strongly associated with reduced readmissions rates.
Preclinical and preliminary clinical data indicate that ch14.18, a monoclonal antibody against the tumor-associated disialoganglioside GD2, has activity against neuroblastoma and that such activity ...is enhanced when ch14.18 is combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2. We conducted a study to determine whether adding ch14.18, GM-CSF, and interleukin-2 to standard isotretinoin therapy after intensive multimodal therapy would improve outcomes in high-risk neuroblastoma.
Patients with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation were randomly assigned, in a 1:1 ratio, to receive standard therapy (six cycles of isotretinoin) or immunotherapy (six cycles of isotretinoin and five concomitant cycles of ch14.18 in combination with alternating GM-CSF and interleukin-2). Event-free survival and overall survival were compared between the immunotherapy group and the standard-therapy group, on an intention-to-treat basis.
A total of 226 eligible patients were randomly assigned to a treatment group. In the immunotherapy group, a total of 52% of patients had pain of grade 3, 4, or 5, and 23% and 25% of patients had capillary leak syndrome and hypersensitivity reactions, respectively. With 61% of the number of expected events observed, the study met the criteria for early stopping owing to efficacy. The median duration of follow-up was 2.1 years. Immunotherapy was superior to standard therapy with regard to rates of event-free survival (66±5% vs. 46±5% at 2 years, P=0.01) and overall survival (86±4% vs. 75±5% at 2 years, P=0.02 without adjustment for interim analyses).
Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a significantly improved outcome as compared with standard therapy in patients with high-risk neuroblastoma. (Funded by the National Institutes of Health and the Food and Drug Administration; ClinicalTrials.gov number, NCT00026312.)
The therapeutic potential of host-specific and tumour-specific immune responses is well recognized and, after many years, active immunotherapies directed at inducing or augmenting these responses are ...entering clinical practice. Antitumour immunization is a complex, multi-component task, and the optimal combinations of antigens, adjuvants, delivery vehicles and routes of administration are not yet identified. Active immunotherapy must also address the immunosuppressive and tolerogenic mechanisms deployed by tumours. This Review provides an overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens and discusses their implications for the use of active immunotherapy.
Consultation for liver disease in pregnant women is a common and oftentimes vexing clinical consultation for the gastroenterologist. The challenge lies in the need to consider the safety of both the ...expectant mother and the unborn fetus in the clinical management decisions. This practice guideline provides an evidence-based approach to common diagnostic and treatment challenges of liver disease in pregnant women.
Cirrhosis results from progressive fibrosis and is the final outcome of all chronic liver disease.It is among the ten leading causes of death in United States.Cirrhosis can result in portal ...hypertension and/or hepatic dysfunction.Both of these either alone or in combination can lead to many complications,including ascites,varices,hepatic encephalopathy,hepatocellular carcinoma,hepatopulmonary syndrome,and coagulation disorders.Cirrhosis and its complications not only impair quality of life but also decrease survival.Managing patients with cirrhosis can be a challenge and requires an organized and systematic approach.Increasing physicians’knowledge about prevention and treatment of these potential complications is important to improve patient outcomes.A literature search of the published data was performed to provide a comprehensive review regarding the management of cirrhosis and its complications.
Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is ...unclear.
To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables.
PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked.
Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder.
Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies.
Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes.
D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.
Objective: To examine predictors and moderators of response to cognitive behavioral therapy (CBT) and medication treatments for binge-eating disorder (BED). Method: 108 BED patients in a randomized ...double-blind placebo-controlled trial testing CBT and fluoxetine treatments were assessed prior, throughout, and posttreatment. Demographic factors, psychiatric and personality disorder comorbidity, eating disorder psychopathology, psychological features, and 2 subtyping methods (negative affect, overvaluation of shape/weight) were tested as predictors and moderators for the primary outcome of remission from binge eating and 4 secondary dimensional outcomes (binge-eating frequency, eating disorder psychopathology, depression, and body mass index). Mixed-effects models analyzed all available data for each outcome variable. In each model, effects for baseline value and treatment were included with tests of both prediction and moderator effects. Results: Several demographic and clinical variables significantly predicted and/or moderated outcomes. One demographic variable signaled a statistical advantage for medication only (younger participants had greater binge-eating reductions), whereas several demographic and clinical variables (lower self-esteem, negative affect, and overvaluation of shape/weight) signaled better improvements if receiving CBT. Overvaluation was the most salient predictor/moderator of outcomes. Overvaluation significantly predicted binge-eating remission (29% of participants with vs. 57% of participants without overvaluation remitted). Overvaluation was especially associated with lower remission rates if receiving medication only (10% vs. 42% for participants without overvaluation). Overvaluation moderated dimensional outcomes: Participants with overvaluation had significantly greater reductions in eating disorder psychopathology and depression levels if receiving CBT. Overvaluation predictor/moderator findings persisted after controlling for negative affect. Conclusions: Our findings have clinical utility for prescription of CBT and medication and implications for refinement of the BED diagnosis.
The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to ...identify potential risk factors for severe illness.
In this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression.
The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53-78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30).
In hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.
In principle, proton therapy offers a substantial clinical advantage over conventional photon therapy. This is because of the unique depth-dose characteristics of protons, which can be exploited to ...achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may, in turn, allow escalation of tumor doses and greater sparing of normal tissues, thus potentially improving local control and survival while at the same time reducing toxicity and improving quality of life.
Protons, accelerated to therapeutic energies ranging from 70 to 250MeV, typically with a cyclotron or a synchrotron, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry. The initial thin beams of protons are spread laterally and longitudinally and shaped appropriately to deliver treatments. Spreading and shaping can be achieved by electro-mechanical means to treat the patients with “passively-scattered proton therapy” (PSPT) or using magnetic scanning of thin “beamlets” of protons of a sequence of initial energies. The latter technique can be used to treat patients with optimized intensity modulated proton therapy (IMPT), the most powerful proton modality.
Despite the high potential of proton therapy, the clinical evidence supporting the broad use of protons is mixed. It is generally acknowledged that proton therapy is safe, effective and recommended for many types of pediatric cancers, ocular melanomas, chordomas and chondrosarcomas. Although promising results have been and continue to be reported for many other types of cancers, they are based on small studies. Considering the high cost of establishing and operating proton therapy centers, questions have been raised about their cost effectiveness. General consensus is that there is a need to conduct randomized trials and/or collect outcomes data in multi-institutional registries to unequivocally demonstrate the advantage of protons.
Treatment planning and plan evaluation of PSPT and IMPT require special considerations compared to the processes used for photon treatment planning. The differences in techniques arise from the unique physical properties of protons but are also necessary because of the greater vulnerability of protons to uncertainties, especially from inter- and intra-fractional variations in anatomy. These factors must be considered in designing as well as evaluating treatment plans. In addition to anatomy variations, other sources of uncertainty in dose delivered to the patient include the approximations and assumptions of models used for computing dose distributions for planning of treatments. Furthermore, the relative biological effectiveness (RBE) of protons is simplistically assumed to have a constant value of 1.1. In reality, the RBE is variable and a complex function of the energy of protons, dose per fraction, tissue and cell type, end point, etc.
These uncertainties, approximations and current technological limitations of proton therapy may limit the achievement of its true potential. Ongoing research is aimed at better understanding the consequences of the various uncertainties on proton therapy and reducing the uncertainties through image-guidance, adaptive radiotherapy, further study of biological properties of protons and the development of novel dose computation and optimization methods. However, residual uncertainties will remain in spite of the best efforts. To increase the resilience of dose distributions in the face of uncertainties and improve our confidence in dose distributions seen on treatment plans, robust optimization techniques are being developed and implemented. We assert that, with such research, proton therapy will be a commonly applied radiotherapy modality for most types of solid cancers in the near future.
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