Abstract Introduction Perforated appendicitis is a common condition in children, which, in a small number of patients, may be complicated by a well-formed abscess. Initial nonoperative management ...with percutaneous drainage/aspiration of the abscess followed by intravenous antibiotics usually allows for an uneventful interval appendectomy. Although this strategy has become well accepted, there are no published data comparing initial nonoperative management (drainage/interval appendectomy) to appendectomy upon presentation with an abscess. Therefore, we conducted a randomized trial comparing these 2 management strategies. Methods After internal review board approval (#06 11-164), children who presented with a well-defined abdominal abscess by computed tomographic imaging were randomized on admission to laparoscopic appendectomy or intravenous antibiotics with percutaneous drainage of the abscess (when possible), followed by interval laparoscopic appendectomy approximately 10 weeks later. This was a pilot study with a sample size of 40, which was based on our recent volume of patients presenting with appendicitis and abscess. Results On presentation, there were no differences between the 2 groups regarding age, weight, body mass index, sex distribution, temperature, leukocyte count, number of abscesses, or greatest 2-dimensional area of abscess in the axial view. Regarding outcomes, there were no differences in length of total hospitalization, recurrent abscess rates, or overall charges. There was a trend toward a longer operating time in patients undergoing initial appendectomy (61 minutes versus 42 minutes mean, P = .06). Conclusions Although initial laparoscopic appendectomy trends toward a requiring longer operative time, there seems to be no advantages between these strategies in terms of total hospitalization, recurrent abscess rate, or total charges.
This study presents observations of atmospheric boundary layer CO2 mole fraction from a nine-tower regional network deployed during the North American Carbon Program's Mid-Continent Intensive (MCI) ...during 2007-2009. The MCI region is largely agricultural, with well-documented carbon exchange available via agricultural inventories. By combining vegetation maps and tower footprints, we show the fractional influence of corn, soy, grass, and forest biomes varies widely across the MCI. Differences in the magnitude of CO2 flux from each of these biomes lead to large spatial gradients in the monthly averaged CO2 mole fraction observed in the MCI. In other words, the monthly averaged gradients are tied to regional patterns in net ecosystem exchange (NEE). The daily scale gradients are more weakly connected to regional NEE, instead being governed by local weather and large-scale weather patterns. With this network of tower-based mole fraction measurements, we detect climate-driven interannual changes in crop growth that are confirmed by satellite and inventory methods. These observations show that regional-scale CO2 mole fraction networks yield large, coherent signals governed largely by regional sources and sinks of CO2.
Abstract Purpose Management of empyema has been debated in the literature for decades. Although both primary video-assisted thoracoscopic surgery (VATS) and tube thoracostomy with pleural ...instillation of fibrinolytics have been shown to result in early resolution when compared to tube thoracostomy alone, there is a lack of comparative data between these modes of management. Therefore, we conducted a prospective, randomized trial comparing VATS to fibrinolytic therapy in children with empyema. Methods After Institutional Review Board approval, children defined as having empyema by either loculation on imaging or more than 10,000 white blood cells/ μ L were treated with VATS or fibrinolysis. Based on our retrospective data using length of postoperative hospitalization as the primary end point, a sample size of 36 patients was calculated for an α of .5 and a power of 0.8. Fibrinolysis consisted of inserting a 12F chest tube followed by infusion of 4 mg tissue plasminogen activator mixed with 40 mL of normal saline at the time of tube placement followed by 2 subsequent doses 24 hours apart. Results At diagnosis, there were no differences between groups in age, weight, degree of oxygen support, white blood cell count, or days of symptoms. The outcome data showed no difference in days of hospitalization after intervention, days of oxygen requirement, days until afebrile, or analgesic requirements. Video-assisted thoracoscopic surgery was associated with significantly higher charges. Three patients (16.6%) in the fibrinolysis group subsequently required VATS for definitive therapy. Two patients in the VATS group required ventilator support after therapy, one of whom required temporary dialysis. No patient in the fibrinolysis group clinically worsened after initiation of therapy. Conclusions There are no therapeutic or recovery advantages between VATS and fibrinolysis for the treatment of empyema; however, VATS resulted in significantly greater charges. Fibrinolysis may pose less risk of acute clinical deterioration and should be the first-line therapy for children with empyema.
Abstract The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 and single work groups in 2012 and 2018 to create recommendations for the ...diagnosis and characterization of Alzheimer's disease (AD). The present document updates the 2018 research framework in response to several recent developments. Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine (e.g., oncology), and is becoming a unifying concept common to all neurodegenerative diseases, not just AD. The present document is consistent with this principle. Our intent is to present objective criteria for diagnosis and staging AD, incorporating recent advances in biomarkers, to serve as a bridge between research and clinical care. These criteria are not intended to provide step‐by‐step clinical practice guidelines for clinical workflow or specific treatment protocols, but rather serve as general principles to inform diagnosis and staging of AD that reflect current science. Highlights We define Alzheimer's disease (AD) to be a biological process that begins with the appearance of AD neuropathologic change (ADNPC) while people are asymptomatic. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms. Early‐changing Core 1 biomarkers (amyloid positron emission tomography PET, approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers especially phosphorylated tau 217) map onto either the amyloid beta or AD tauopathy pathway; however, these reflect the presence of ADNPC more generally (i.e., both neuritic plaques and tangles). An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum. Later‐changing Core 2 biomarkers (biofluid and tau PET) can provide prognostic information, and when abnormal, will increase confidence that AD is contributing to symptoms. An integrated biological and clinical staging scheme is described that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages.
National-scale emissions of carbon tetrachloride (CCl₄) are derived based on inverse modeling of atmospheric observations at multiple sites across the United States from the National Oceanic and ...Atmospheric Administration’s flask air sampling network. We estimate an annual average US emission of 4.0 (2.0–6.5) Gg CCl₄ y−1 during 2008–2012, which is almost two orders of magnitude larger than reported to the US Environmental Protection Agency (EPA) Toxics Release Inventory (TRI) (mean of 0.06 Gg y−1) but only 8% (3–22%) of global CCl₄ emissions during these years. Emissive regions identified by the observations and consistently shown in all inversion results include the Gulf Coast states, the San Francisco Bay Area in California, and the Denver area in Colorado. Both the observation-derived emissions and the US EPA TRI identified Texas and Louisiana as the largest contributors, accounting for one- to two-thirds of the US national total CCl₄ emission during 2008–2012. These results are qualitatively consistent with multiple aircraft and ship surveys conducted in earlier years, which suggested significant enhancements in atmospheric mole fractions measured near Houston and surrounding areas. Furthermore, the emission distribution derived for CCl₄ throughout the United States is more consistent with the distribution of industrial activities included in the TRI than with the distribution of other potential CCl₄ sources such as uncapped landfills or activities related to population density (e.g., use of chlorine-containing bleach).
Objective:
The efficacy of galcanezumab was evaluated in patients with episodic cluster headache and history of preventive treatment failure.
Methods:
In the randomized, 8-week, double-blind study ...(CGAL), patients with episodic cluster headache received once-monthly subcutaneous injections of galcanezumab 300 mg or placebo. Patients who completed CGAL and enrolled in an open-label study were queried for preventive treatment history. In a subset of patients with a known history of failure of verapamil or any other prior preventive treatment, a post hoc analysis of least square mean change from baseline in weekly cluster headache attack frequency across Weeks 1 to 3 was assessed.
Results:
Fifteen patients provided data for known history of prior preventive treatment failure (6 placebo, 9 galcanezumab), of whom 11 failed verapamil. The mean reduction in the weekly frequency of cluster headache attacks was greater with galcanezumab compared to placebo among patients with prior preventive treatment failure (8.2 versus 2.4); mean difference 5.8 (95% confidence interval CI 2.0, 13.6) and among patients with verapamil failure (10.1 versus 1.6); mean difference 8.5 (95% CI 0.4, 16.7).
Conclusion:
In this exploratory analysis of patients with a known history of prior preventive treatment failures, treatment with galcanezumab resulted in greater mean reductions in weekly cluster headache attacks compared with placebo.
ClinicalTrials.gov:
NCT02397473 (I5Q-MC-CGAL)
NCT02797951 (I5Q-MC-CGAR)
Ozone depleting substances (ODSs) controlled by the Montreal Protocol are potent greenhouse gases (GHGs), as are their substitutes, the hydrofluorocarbons (HFCs). Here we provide for the first time a ...comprehensive estimate of U.S. emissions of ODSs and HFCs based on precise measurements in discrete air samples from across North America and in the remote atmosphere. Derived emissions show spatial and seasonal variations qualitatively consistent with known uses and largely confirm U.S. Environmental Protection Agency (EPA) national emissions inventories for most gases. The measurement‐based results further indicate a substantial decline of ODS emissions from 2008 to 2014, equivalent to ~50% of the CO2‐equivalent decline in combined emissions of CO2 and all other long‐lived GHGs inventoried by the EPA for the same period. Total estimated CO2‐equivalent emissions of HFCs were comparable to the sum of ODS emissions in 2014, but can be expected to decline in the future in response to recent policy measures.
Key Points
Atmospheric data indicate substantial declines in United States emissions of ozone‐depleting substances owing to the Montreal Protocol
The emission decline is also substantial compared to the decline in total emissions of CO2 and other major greenhouse gases
Spatial distribution and seasonality of derived emissions for ozone‐depleting gases and hydrofluorocarbons are consistent with their uses
Improved treatment for major depressive disorder (MDD) remains elusive because of the limited understanding of its underlying biological mechanisms. It is likely that stress-induced maladaptive ...transcriptional regulation in limbic neural circuits contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin structure. We establish that persistent upregulation of the ACF (ATP-utilizing chromatin assembly and remodeling factor) ATP-dependent chromatin-remodeling complex, occurring in the nucleus accumbens of stress-susceptible mice and depressed humans, is necessary for stress-induced depressive-like behaviors. We found that altered ACF binding after chronic stress was correlated with altered nucleosome positioning, particularly around the transcription start sites of affected genes. These alterations in ACF binding and nucleosome positioning were associated with repressed expression of genes implicated in susceptibility to stress. Together, our findings identify the ACF chromatin-remodeling complex as a critical component in the development of susceptibility to depression and in regulating stress-related behaviors.
Abstract Objective To assess the cost-effectiveness of duloxetine in the treatment of chronic low back pain (CLBP) from a US private payer perspective. Methods A cost-utility analysis was undertaken ...for duloxetine and seven oral post–first-line comparators, including nonsteroidal anti-inflammatory drugs (NSAIDs), weak and strong opioids, and an anticonvulsant. We created a Markov model on the basis of the National Institute for Health and Clinical Excellence model documented in its 2008 osteoarthritis clinical guidelines. Health states included treatment, death, and 12 states associated with serious adverse events (AEs). We estimated treatment-specific utilities by carrying out a meta-analysis of pain scores from CLBP clinical trials and developing a transfer-to-utility equation using duloxetine CLBP patient-level data. Probabilities of AEs were taken from the National Institute for Health and Clinical Excellence model or estimated from osteoarthritis clinical trials by using a novel maximum-likelihood simulation technique. Costs were gathered from Red Book, Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project database, the literature, and, for a limited number of inputs, expert opinion. The model performed one-way and probabilistic sensitivity analyses and generated incremental cost-effectiveness ratios (ICERs) and cost acceptability curves. Results The model estimated an ICER of $59,473 for duloxetine over naproxen. ICERs under $30,000 were estimated for duloxetine over non-NSAIDs, with duloxetine dominating all strong opioids. In subpopulations at a higher risk of NSAID-related AEs, the ICER over naproxen was $33,105 or lower. Conclusions Duloxetine appears to be a cost-effective post–first-line treatment for CLBP compared with all but generic NSAIDs. In subpopulations at risk of NSAID-related AEs, it is particularly cost-effective.
Introduction
Research has shown increased health‐care resource use (HRU) among patients with Alzheimer's disease and related disorders (ADRD) well before diagnosis, but the degree to which HRU is ...correlated with disease severity at the time of initial assessment is not well documented.
Methods
Retrospective analysis of linked medical records and claims data for three cohorts: mild ADRD (first index Mini‐Mental State Examination MMSE ≥20), moderate/severe ADRD (index MMSE < 20), controls without cognitive impairment. HRU during the pre‐index year was compared using multivariate regressions.
Results
ADRD cohorts had significantly (P < .01) higher HRU than controls. Compared to mild ADRD patients, moderate/severe ADRD patients had higher rates of hospitalizations (relative risk RR: 1.57), emergency department visits (RR: 1.36), potentially avoidable hospitalizations (RR: 1.72), and accidental falls (RR: 1.58).
Discussion
HRU before initial assessment increases with disease severity at the time of assessment, highlighting the need for timely evaluation and improved management in the earliest stages of ADRD.
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