Objective To examine the predictive ability of stage of hypoxic-ischemic encephalopathy (HIE) for death or moderate/severe disability at 18 months among neonates undergoing hypothermia. Study design ...Stage of encephalopathy was evaluated at <6 hours of age, during study intervention, and at discharge among 204 participants in the National Institute of Child Health and Human Development Neonatal Research Network Trial of whole body hypothermia for HIE. HIE was examined as a predictor of outcome by regression models. Results Moderate and severe HIE occurred at <6 hours of age among 68% and 32% of 101 hypothermia group infants and 60% and 40% of 103 control group infants, respectively. At 24 and 48 hours of study intervention, infants in the hypothermia group had less severe HIE than infants in the control group. Persistence of severe HIE at 72 hours increased the risk of death or disability after controlling for treatment group. The discharge exam improved the predictive value of stage of HIE at <6 hours for death/disability. Conclusions On serial neurologic examinations, improvement in stage of HIE was associated with cooling. Persistence of severe HIE at 72 hours and an abnormal neurologic exam at discharge were associated with a greater risk of death or disability.
Background Plasma exchange may be effective adjunctive treatment for renal vasculitis. We performed a systematic review and meta-analysis of randomized controlled trials of plasma exchange for renal ...vasculitis. Study Design Systematic review and meta-analysis of articles identified from electronic databases, bibliographies, and studies identified by experts. Data were abstracted in parallel by 2 reviewers. Setting & Population Adults with idiopathic renal vasculitis or rapidly progressive glomerulonephritis. Selection Criteria for Studies Randomized controlled trials that compared standard care with standard care plus adjuvant plasma exchange in adult patients with either renal vasculitis or idiopathic rapidly progressive glomerulonephritis. Intervention Adjuvant plasma exchange. Outcome Composite of end-stage renal disease or death. Results We identified 9 trials including 387 patients. In a fixed-effects model, the pooled RR for end-stage renal disease or death was 0.80 for patients treated with adjunctive plasma exchange compared with standard care alone (95% CI, 0.65-0.99; P = 0.04). No significant heterogeneity was detected ( P = 0.5; I2 = 0%). The effect of plasma exchange did not differ significantly across the range of baseline serum creatinine values ( P = 0.7) or number of plasma exchange treatments ( P = 0.8). The RR for end-stage renal disease was 0.64 (95% CI, 0.47-0.88; P = 0.006), whereas the RR for death alone was 1.01 (95% CI, 0.71-1.4; P = 0.9). Limitations Although the primary result was statistically significant, there is insufficient statistical information to reliably determine whether plasma exchange decreases the composite of end-stage renal disease or death. Conclusions Plasma exchange may decrease the composite end point of end-stage renal disease or death in patients with renal vasculitis. Additional trials are required given the limited data available.
Management of Primary Pulmonary Artery Sarcomas Blackmon, Shanda H., MD, MPH; Rice, David C., MMB, BCh; Correa, Arlene M., PhD ...
The Annals of thoracic surgery,
03/2009, Letnik:
87, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The objective of this review is to determine the outcome of patients with sarcomas involving the main pulmonary artery, pulmonic valve, or right ventricular outflow tract. Survival data were analyzed ...using an aggregate series derived from the published literature in conjunction with a current series. Median survival was 36.5 ± 20.2 months for patients undergoing an attempt at curative resection compared with 11 ± 3 months for those undergoing incomplete resection. Median survival was 24.7 ± 8.5 months for patients undergoing multimodality treatment compared with 8.0 ± 1.7 months for patients having single-modality therapy. A complete review of diagnosis, evaluation, treatment, and surveillance of primary pulmonary artery sarcomas follows.
Pulmonary vascular leakage occurs early in acute respiratory distress syndrome (ARDS). Mortality is high (35-45%), but no effective pharmacotherapy exists. Production of anti-inflammatory adenosine ...by ecto-5'-nucleotidase (CD73) helps maintain endothelial barrier function. We tested whether interferon-beta-1a (IFN-beta-1a), which increases CD73 synthesis, can reduce vascular leakage and mortality in patients with ARDS.
In ex-vivo studies, we first established that IFN-beta-1a induced CD73 up-regulation in cultured human lung tissue samples. We then tested the safety, tolerability, and efficacy of intravenous human recombinant IFN-beta-1a (FP-1201) in patients with ARDS in an open-label study (comprising dose-escalation and expansion phases). We recruited patients from eight intensive care units in the UK. Eligible patients were aged 18 years or older, had ARDS, and were being treated with assisted ventilation. We established an optimal tolerated dose (OTD) in the first, dose-escalation phase. Once established, we gave all subsequently enrolled patients the OTD of intravenous FP-1201 for 6 days. We assessed 28-day mortality (our primary endpoint) in all patients receiving the OTD versus 28-day mortality in a group of patients who did not receive treatment (this control group comprised patients in the study but who did not receive treatment because they were screened during the safety windows after dose escalation). This trial is registered with ClinicalTrials.gov, number NCT00789685, and the EU Clinical Trials Register EudraCT, number 2008-000140-13.
IFN-beta-1a increased the number of CD73-positive vessels in lung culture by four times on day 1 (p=0·04) and by 14·3 times by day 4 (p=0·004). For the clinical trial, between Feb 23, 2009, and April 7, 2011, we identified 150 patients, of whom 37 were enrolled into the trial and given treatment. The control group consisted of 59 patients who were recruited to take part in the study, but who did not receive treatment. Demographic characteristics and severity of illness did not differ between treatment and control groups. The optimal tolerated FP-1201 dose was 10 μg per day for 6 days. By day 28, 3 (8%) of 37 patients in the treatment cohort and 19 (32%) of 59 patients in the control cohort had died-thus, treatment with FP-1201 was associated with an 81% reduction in odds of 28-day mortality (odds ratio 0·19 95% CI 0·03-0·72; p=0·01).
FP-1201 up-regulates human lung CD73 expression, and is associated with a reduction in 28-day mortality in patients with ARDS. Our findings need to be substantiated in large, prospective randomised trials, but suggest that FP-1201 could be the first effective, mechanistically targeted, disease-specific pharmacotherapy for patients with ARDS.
Bleeding is the most common adverse event in those with cardiovascular (CV) disease receiving antithrombotic therapy, and it most commonly occurs in the gastrointestinal (GI) tract. Clinicians often ...dismiss bleeding as an adverse event that is reversible with effective antithrombotic therapy, but bleeding is associated with substantial morbidity and mortality, most likely mediated through an increased risk of CV events. Reducing the burden of bleeding requires knowledge of the potentially modifiable risk factors for bleeding and the potentially modifiable risk factors for adverse outcomes after bleeding.
INTERBLEED is an international, multicentre, 2-component, observational study, with an incident case-control study examining the risk factors for GI bleeding, and a prospective cohort study of risk factors for CV events after GI bleeding. Cases either have CV disease and present to the hospital with GI bleeding or develop GI bleeding during hospitalization. Controls have CV disease, but no history of GI bleeding. We use a questionnaire to obtain detailed information on known and potential risk factors for GI bleeding and for CV events and outcomes after bleeding. We obtain CV and anthropometric measurements, perform functional and cognitive assessments, and follow participants at 3 months and 12 months.
As of April 1, 2022, the study is ongoing in 10 countries at 31 centres and has recruited 2407 cases and 1478 controls.
Knowledge of risk factors for bleeding, and risk factors for CV events and functional decline after bleeding, will help develop strategies to prevent bleeding and subsequent complications.
L’hémorragie est l’effet indésirable le plus fréquent chez les patients atteints de maladies cardiovasculaires (CV) qui reçoivent un traitement antithrombotique, et elle survient le plus souvent dans le tractus gastro-intestinal (GI). Les cliniciens considèrent souvent l’hémorragie comme une simple manifestation indésirable réversible par un traitement antithrombotique efficace, mais une morbidité et une mortalité considérables y sont associées, probablement en raison d’un risque accru d’événements CV. Une réduction du fardeau de l’hémorragie nécessite une connaissance des facteurs de risque potentiellement modifiables tant de l’hémorragie que des événements indésirables qui surviennent après l’hémorragie.
INTERBLEED est une étude internationale, observationnelle et multicentrique à deux volets; le premier volet est une étude cas-témoins incidents visant à examiner les facteurs de risque d’hémorragie GI, alors que le second volet est une étude de cohorte prospective visant à examiner les facteurs de risque d’événements CV après une hémorragie GI. Les cas sont des patients atteints de maladies CV qui consultent les services hospitaliers pour une hémorragie GI ou qui présentent une hémorragie GI en cours d’hospitalisation. Les témoins sont des patients atteints de maladies CV, mais sans antécédents d’hémorragie GI. Un questionnaire est utilisé pour obtenir des renseignements détaillés au sujet de facteurs de risque connus et potentiels d’hémorragie GI et d’événements CV et d’autres résultats de santé après une hémorragie. Des mesures cardiovasculaires et anthropométriques ainsi que des évaluations fonctionnelles et cognitives sont réalisées, et les participants sont revus après trois mois et 12 mois.
En date du 1er avril 2022, l’étude est en cours dans 10 pays et 31 établissements de santé; 2 407 cas et 1 478 témoins ont été recrutés.
La connaissance des facteurs de risque d’hémorragie, ainsi que des facteurs de risque d’événements CV et de déclin fonctionnel à la suite d’une hémorragie, aidera à mettre en place des stratégies pour prévenir les hémorragies et les complications qui peuvent en découler.
Abstract The presentation, natural history, clinical outcomes, and response to therapy in patients with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian ...racial or ethnic groups compose a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under- or overtreatment of these patients. Even when guideline-based treatments are prescribed, socioeconomic, physical, or psychologic factors may affect non-Caucasian and older adult patient groups to a different extent and affect the application, effectiveness, and tolerability of these therapies. Individualized therapy based on tailored biology (genetics, proteomics, metabolomics), socioeconomic and cultural considerations, and individual goals and preferences may be the optimal approach for managing diverse patients. This comprehensive approach to personalized medicine is evolving, but in the interim, the scientific community should continue efforts focused on intensifying research in special populations, prescribing guideline-directed medical therapy unless contraindicated, and implementing evidence-based strategies including patient and family education and multidisciplinary team care in the management of patients.
Conventional antidepressants require 2-8 weeks for a full clinical response. In contrast, two rapidly acting antidepressant interventions, low-dose ketamine and sleep deprivation (SD) therapy, act ...within hours to robustly decrease depressive symptoms in a subgroup of major depressive disorder (MDD) patients. Evidence that MDD may be a circadian-related illness is based, in part, on a large set of clinical data showing that diurnal rhythmicity (sleep, temperature, mood and hormone secretion) is altered during depressive episodes. In a microarray study, we observed widespread changes in cyclic gene expression in six regions of postmortem brain tissue of depressed patients matched with controls for time-of-death (TOD). We screened 12 000 transcripts and observed that the core clock genes, essential for controlling virtually all rhythms in the body, showed robust 24-h sinusoidal expression patterns in six brain regions in control subjects. In MDD patients matched for TOD with controls, the expression patterns of the clock genes in brain were significantly dysregulated. Some of the most robust changes were seen in anterior cingulate (ACC). These findings suggest that in addition to structural abnormalities, lesion studies, and the large body of functional brain imaging studies reporting increased activation in the ACC of depressed patients who respond to a wide range of therapies, there may be a circadian dysregulation in clock gene expression in a subgroup of MDDs. Here, we review human, animal and neuronal cell culture data suggesting that both low-dose ketamine and SD can modulate circadian rhythms. We hypothesize that the rapid antidepressant actions of ketamine and SD may act, in part, to reset abnormal clock genes in MDD to restore and stabilize circadian rhythmicity. Conversely, clinical relapse may reflect a desynchronization of the clock, indicative of a reactivation of abnormal clock gene function. Future work could involve identifying specific small molecules capable of resetting and stabilizing clock genes to evaluate if they can rapidly relieve symptoms and sustain improvement.
We review clinical care issues that are related to illicit and therapeutic opioid use among pregnant women and women in the postpartum period and outline the major responsibilities of obstetrics ...providers who care for these patients during the antepartum, intrapartum, and postpartum periods. Selected patient treatment issues are highlighted, and case examples are provided. Securing a strong rapport and trust with these patients is crucial for success in delivering high-quality obstetric care and in coordinating services with other specialists as needed. Obstetrics providers have an ethical obligation to screen, assess, and provide brief interventions and referral to specialized treatment for patients with drug use disorders. Opioid-dependent pregnant women often can be treated effectively with methadone or buprenorphine. These medications are classified as pregnancy category C medications by the Food and Drug Administration, and their use in the treatment of opioid-dependent pregnant patients should not be considered “off-label.” Except in rare special circumstances, medication-assisted withdrawal during pregnancy should be discouraged because of a high relapse rate. Acute pain management in this population deserves special consideration because patients who use opioids can be hypersensitive to pain and because the use of mixed opioid-agonist/antagonists can precipitate opioid withdrawal. In the absence of other indications, pregnant women who use opioids do not require more intense medical care than other pregnant patients to ensure adequate treatment and the best possible outcomes. Together with specialists in pain and addiction medicine, obstetricians can coordinate comprehensive care for pregnant women who use opioids and women who use opioids in the postpartum period.
A revised set of propositions about ecology in arid Australia is presented, based on research literature since publication of Stafford Smith and Morton (1990). Fourteen propositions distil our ...argument that most features of the Australian deserts are explicable in terms of two dominant physical and climatic elements: rainfall variability, leading to extended droughts and occasional flooding rains; and widespread nutrient poverty. Different landscapes within the arid zone show these features to varying degrees, and so it is important to think about different places separately when considering our propositions. Plant life-histories strongly reflect temporal patterns of soil moisture; because Australian deserts receive more variable rainfall than most others, there is a distinctive spectrum of life-histories. Low levels of phosphorus (together with abundant soil moisture on irregular occasions) favour plants producing a relative excess of carbohydrate (C). In turn, C-rich plant products sometimes lead to fire-prone ecosystems, assemblages dominated by consumers of sap and other C-based products, and abundant detritivores (particularly termites). Fluctuations in production due to variable rainfall provide openings for consumers with opportunistic life-histories, including inhabitants of extensive but ephemeral rivers and lakes. Most consumer species exhibit some dietary flexibility or utilise more dependable resources; these strategies give rise to greater stability in species dynamics and composition of assemblages than might first be imagined under the variable rainfall regime. Aboriginal people have had long-standing ecological influence as they accessed resources. For each proposition we suggest the extent to which it is ‘different’, ‘accentuated’ or ‘universal’ in comparison with other deserts of the world, recognising that this categorisation is in need of critical testing. Further tests of each proposition are also suggested to fill the many gaps that still exist in our knowledge of the structure and functioning of Australia’s deserts.
► Revised propositions about arid Australia are presented based on research since Stafford Smith and Morton (1990, Journal of Arid Environments 18, 255-278. ► Australian plant life-histories distinctively reflect variable temporal patterns of soil moisture. ► Low phosphorus levels favour plants producing a relative excess of carbohydrate, leading to fire-proneness and abundant detritivores. ► Irregular fluctuations in production due to variable rainfall encourage consumers with opportunistic life-histories.
Summary Background Suvorexant (MK-4305) is an orexin receptor antagonist shown to be efficacious for insomnia over 3 months. We aimed to assess its clinical profile during and after 1 year of ...treatment. Methods We did a randomised, placebo-controlled, parallel-group trial at 106 investigational centres in the Americas, Australia, Europe, and South Africa from December, 2009, to August, 2011. Patients aged 18 years or older with primary insomnia by DSM-IV-TR criteria were assigned using a computer-generated randomised allocation schedule to receive nightly suvorexant (40 mg for patients younger than 65 years, 30 mg for patients aged 65 years or older) or placebo at a 2:1 ratio for 1 year with a subsequent 2-month randomised discontinuation phase in which patients on suvorexant either continued suvorexant or were abruptly switched to placebo while patients on placebo remained on placebo. Treatment assignment was masked from patients and investigators. The primary objective was to assess the safety and tolerability of suvorexant for up to 1 year. Secondary objectives were to assess the efficacy of suvorexant for improving patient-reported subjective total sleep time (sTST) and time to sleep onset (sTSO) over the first month of treatment. Efficacy endpoints over the first month were assessed with a mixed model with terms for baseline value of the response variable, age, sex, region, treatment, time, and treatment by time interaction. This trial is registered with ClinicalTrials.gov , number NCT01021813. Findings 322 (62%) of 522 patients randomly assigned to receive suvorexant and 162 (63%) of 259 assigned to receive placebo completed the 1-year phase. Over 1 year, 362 (69%) of 521 patients treated with suvorexant experienced any adverse events compared with 164 (64%) of 258 treated with placebo. Serious adverse events were recorded in 27 patients (5%) who received suvorexant and 17 (7%) who received placebo. The most common adverse event, somnolence, was reported for 69 patients (13%) who received suvorexant and seven (3%) who received placebo. At month 1, suvorexant (517 patients in the efficacy population) showed greater efficacy than placebo (254 in the efficacy population) in improving sTST (38·7 min vs 16·0 min; difference 22·7, 95% CI 16·4 to 29·0; p<0·0001) and sTSO (–18·0 min vs −8·4 min, difference −9·5, −14·6 to −4·5; p=0·0002). Interpretation Our findings show that suvorexant was generally safe and well tolerated over 1 year of nightly treatment in patients with insomnia, with efficacy noted for subjective measures of sleep onset and maintenance. Funding Merck & Co Inc.
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