While the opioid epidemic has garnered worldwide attention, increasing methamphetamine use has drawn less scrutiny. Methamphetamine is a highly addictive psychostimulant affecting people from all ...backgrounds and regions. It is a potent vasoconstrictor, is associated with arrhythmias and dilated cardiomyopathy. Cardiovascular disease-related mortality is a leading cause of death in methamphetamine users. Women of childbearing age increasingly use methamphetamine and continue during pregnancy. In the short term, prenatal methamphetamine use is associated with fetal growth restriction and low birth weight in the newborn. Animal studies show reduction in uterine and umbilical blood flow following maternal methamphetamine administration. Based on currently available evidence, prenatal methamphetamine exposure has transient effects on gross motor development, no effect on language and cognition, and modest effects on behavior and executive functioning with poor inhibitory control, which may be attributable to early adversity. Further research is needed to evaluate long-term effects of prenatal methamphetamine exposure.
In August 2022, these guidelines were reviewed by an expert work group convened by ASH. Review included limited searches for new evidence and discussion of the search results. Following this review, ...the ASH Committee on Quality agreed to continue monitoring the supporting evidence rather than revise or retire these guidelines at this time. Limited searches and expert review will be repeated annually going forward until these guidelines are revised or retired.
Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), occurs in ∼1 to 2 individuals per 1000 each year, corresponding to ∼300 000 to 600 000 events in the United States annually.
Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support patients, clinicians, and others in decisions about treatment of VTE.
Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and adult patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.
Results: The panel agreed on 28 recommendations for the initial management of VTE, primary treatment, secondary prevention, and treatment of recurrent VTE events.
Conclusions: Strong recommendations include the use of thrombolytic therapy for patients with PE and hemodynamic compromise, use of an international normalized ratio (INR) range of 2.0 to 3.0 over a lower INR range for patients with VTE who use a vitamin K antagonist (VKA) for secondary prevention, and use of indefinite anticoagulation for patients with recurrent unprovoked VTE. Conditional recommendations include the preference for home treatment over hospital-based treatment for uncomplicated DVT and PE at low risk for complications and a preference for direct oral anticoagulants over VKA for primary treatment of VTE.
What you need to know: The recommendations apply to patients under 60 years old with patent foramen ovale (PFO) who have had a cryptogenic ischaemic stroke, when extensive workup for other ...aetiologies of stroke is negative; For patients who are open to all options, we make a weak recommendation for PFO closure plus antiplatelet therapy rather than anticoagulant therapy; For patients in whom anticoagulation is contraindicated or declined, we make a strong recommendation for PFO closure plus antiplatelet therapy versus antiplatelet therapy alone; For patients in whom closure is contraindicated or declined, we make a weak recommendation for anticoagulant therapy rather than antiplatelet therapy; Further research may alter the recommendations that involve anticoagulant therapy. Options for the secondary prevention of stroke in patients younger than 60 years who have had a cryptogenic ischaemic stroke thought to be secondary to patent foramen ovale (PFO) include PFO closure (with antiplatelet therapy), antiplatelet therapy alone, or anticoagulants. International guidance and practice differ on which option is preferable. The BMJ Rapid Recommendations panel used a linked systematic review1 triggered by three large randomised trials published in September 2017 that suggested PFO closure might reduce the risk of ischaemic stroke more than alternatives.234 The panel felt that the studies, when considered in the context of the full body of evidence, might change current clinical practice.5 The linked systematic review finds that PFO closure prevents recurrent stroke relative to antiplatelet therapy, but possibly not relative to anticoagulants, and is associated with procedural complications and persistent atrial fibrillation.1 The review also presents evidence regarding the role of anticoagulants or antiplatelet therapy when PFO closure is not acceptable or is contraindicated.
IMPORTANCE: The optimal oxygen saturation (SpO2) target for extremely preterm infants is unknown. OBJECTIVE: To systematically review evidence evaluating the effect of restricted vs liberal oxygen ...exposure on morbidity and mortality in extremely preterm infants. DATA SOURCES: MEDLINE, PubMed, CENTRAL, and CINAHL databases from their inception to March 31, 2014, and abstracts submitted to Pediatric Academic Societies from 2000 to 2014. STUDY SELECTION: All published randomized trials evaluating the effect of restricted (SpO2, 85%-89%) vs liberal (SpO2, 91%-95%) oxygen exposure in preterm infants (<28 weeks’ gestation at birth). DATA EXTRACTION AND SYNTHESIS: All meta-analyses were performed using Review Manager 5.2. The Cochrane risk-of-bias tool was used to assess study quality. The summary of the findings and the level of confidence in the estimate of effect were assessed using GRADEpro. Treatment effect was analyzed using a random-effects model. MAIN OUTCOMES AND MEASURES: Death before hospital discharge, death or severe disability before 24 months, death before 24 months, neurodevelopmental outcomes, hearing loss, bronchopulmonary dysplasia, necrotizing enterocolitis, and severe retinopathy of prematurity. RESULTS: Five trials were included in the final synthesis. These studies had a similar design with a prespecified composite outcome of death/disability at 18 to 24 months corrected for prematurity; however, this outcome has not been reported for 2 of the 5 trials. There was no difference in the outcome of death/disability before 24 months (risk ratio RR, 1.02 95% CI, 0.92-1.14). Mortality before 24 months was not different (RR, 1.13 95% CI, 0.97-1.33); however, a significant increase in mortality before hospital discharge was found in the restricted oxygen group (RR, 1.18 95% CI, 1.03-1.36). The rates of bronchopulmonary dysplasia, neurodevelopmental outcomes, hearing loss, and retinopathy of prematurity were similar between the 2 groups. Necrotizing enterocolitis occurred more frequently in infants on restricted oxygen (RR, 1.24 95% CI, 1.05-1.47). Using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria, we found that the quality of evidence for these outcomes was moderate to low. CONCLUSIONS AND RELEVANCE: Although infants cared for with a liberal oxygen target had significantly lower mortality before hospital discharge than infants cared for with a restricted oxygen target, the quality of evidence for this estimate of effect is low. Necrotizing enterocolitis occurred less frequently in the liberal oxygen group. We found no significant differences in death or disability at 24 months, bronchopulmonary dysplasia, retinopathy of prematurity, neurodevelopmental outcomes, or hearing loss at 24 months.
Abstract Background Composite end points are frequently used in reports of clinical trials. One rationale for the use of composite end points is to account for competing risks. In the presence of ...competing risks, the event rate of a specific event depends on the rates of other competing events. One proposed solution is to include all important competing events in one composite end point. Clinical trialists require guidance regarding when this approach is appropriate. Objectives To identify publications describing criteria for use of composite end points for competing risk and to offer guidance regarding when a composite end point is appropriate on the basis of competing risks. Methods, Data Sources, Study Selection and Data Extraction We searched MEDLINE, CINAHL, EMBASE, The Cochrane's Central & Systematic Review databases including the Health Technology Assessment database, and the Cochrane's Methodology register from inception to April 2015, and candidate textbooks, to identify all articles providing guidance on this issue. Eligible publications explicitly addressed the issue of a composite outcome to address competing risks. Two reviewers independently screened the titles and abstracts for full-text review; independently reviewed full-text publications; and abstracted specific criteria authors offered for use of composite end points to address competing risks. Results Of 63,645 titles and abstracts, 166 proved potentially relevant of which 43 publications were included in the final review. Most publications note competing risks as a reason for using composite end points without further elaboration. None of the articles or textbook chapters provide specific criteria for use of composite end points for competing risk. Some advocate using composite end points to avoid bias due to competing risks and others suggest that composite end points seldom or never be used for this purpose. We recommend using composite end points for competing risks only if the competing risk is plausible and if it occurs with sufficiently high frequency to influence the interpretation of the effect of intervention on the end point of interest. These criteria will seldom be met. Review of heart failure trials published in the New England Journal of Medicine revealed that many of them use the composite end point of death or hospitalization; none of the trials, however, satisfied our criteria. Conclusion The existing literature fails to provide clear guidance regarding use of composite end point for competing risks. We recommend using composite end points for competing risks only if the competing risk is plausible and if it occurs sufficiently often.
The optimal oxygen saturation target for extremely preterm infants remains unclear.
To systematically review evidence evaluating the effect of lower (85%-89%) versus higher (91%-95%) pulse oxygen ...saturation (Spo
) target on mortality and neurodevelopmental impairment (NDI) at 18 to 24 months.
Electronic databases and all published randomized trials evaluating lower versus higher Spo
target in preterm infants.
A total of 2896 relevant citations were identified; 5 trials were included in the final analysis.
Data from 5 trials were analyzed for quality of evidence and risk of bias.
Limitations include heterogeneity in age at enrollment and comorbidities between trials and change in oximeter algorithm midway through 3 trials.
There was no difference in the incidence of primary outcome (death/NDI at 18-24 months) in the 2 groups; risk ratio,1.05, 95% confidence interval 0.98-1.12, P = .18. Mortality before 18 to 24 months was higher in the lower-target group (risk ratio,1.16, 95% confidence interval 1.03-1.31, P = .02). Rates of NDI and severe visual loss did not differ between the 2 groups. Proportion of time infants spent outside the target range while on supplemental oxygen ranged from 8.2% to 27.4% <85% and 8.1% to 22.4% >95% with significant overlap between the 2 groups.
There was no difference in primary outcome between the 2 Spo
target groups. The collective data suggest that risks associated with restricting the upper Spo
target limit to 89% outweigh the benefits. The quality of evidence was moderate. We speculate that a wider target range (lower alarm limit, 89% and upper, 96%) may increase time spent within range, but the safety profile of this approach remains to be determined.
Healthcare costs are increasing in the USA and Canada and a substantial portion of health spending is devoted to services that do not improve health outcomes. Efforts to reduce waste by adopting ...evidence-based clinical practice guideline recommendations have had limited success. We sought insight into improving health system efficiency through understanding cardiologists' perceptions of factors that influence clinical decision-making.
In this descriptive qualitative study, we conducted in-depth interviews with 18 American and 3 Canadian cardiologists. We used conventional content analysis including inductive and deductive approaches for data analysis and mapped findings to the ecological systems framework.
Physicians reported that major determinants of practice included interpersonal interactions with peers, patients and administrators; financial incentives and system factors. Patients' insurance status represented an important consideration for some cardiologists. Other major influences included time constraints, fear of litigation (less prominent in Canada), a sense that their obligation was never to miss any underlying pathology, and patient demands. The need to bring income into their health system influenced American cardiologists' practice; personal income implications influenced Canadian cardiologists' practice. Cardiologists reported that knowledge limitations and logistical challenges limit their ability to assist patients with cost considerations. All these considerations were more influential than guidelines; some cardiologists expressed a high level of scepticism regarding guidelines.
Clinical decision-making by cardiologists is shaped by individual, interpersonal, organisational, environmental, financial and sociopolitical influences and only to a limited extent by guideline recommendations. Successful strategies to achieve efficient, evidence-based care will require addressing socioecological influences on decision-making.
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