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- Centralized Monitoring and Virtual Consultant Models of Tele-ICU Care: A Systematic Review.Ramnath VR, Ho L, Maggio LA, Khazeni NTelemed J E Health
- A Rapid and Simple Method for DNA Engineering Using Cycled Ligation Assembly.Roth TL, Milenkovic L, Scott MPPLoS One
- Influence of a custom made maxillary mouthguardguard guard on gas exchange parameters during incremental exercise in amateur road cyclists.Piero M, Simone U, Jonathan M, Maria S, Giulio G, Francesco T, Gabriella C, Laura A, Eva B, Gianni M, Francesco C, Giovanni GJ Strength Cond Res
- Predictive Performance of a Gentamicin Population Pharmacokinetic Model in Neonates Receiving Full-Body Hypothermia.Sampson MR, Frymoyer A, Rattray B, Cotten CM, Smith PB, Capparelli E, Bonifacio SL, Cohen-Wolkowiez MTher Drug Monit
- Centralized Monitoring and Virtual Consultant Models of Tele-ICU Care: A Side-by-Side Review.Ramnath VR, Khazeni NTelemed J E Health
- Cellulose Nanoparticles are a Biodegradable Photoacoustic Contrast Agent for Use in Living Mice.Jokerst JV, Van de Sompel D, Bohndiek SE, Gambhir SSPhotoacoustics
- Aesthetic Surgery Training during Residency in the United States: A Comparison of the Integrated, Combined, and Independent Training Models.Momeni A, Kim RY, Wan DC, Izadpanah A, Lee GKPlast Surg Int
- Computational modeling of skin: Using stress profiles as predictor for tissue necrosis in reconstructive surgery.Tepole AB, Gosain AK, Kuhl EComput Struct
- Development and Future of the American Society of Clinical Oncology's Quality Oncology Practice Initiative.Blayney DW, McNiff K, Eisenberg PD, Gilmore T, Jacobsen PB, Jacobson JO, Kadlubek PJ, Neuss MN, Simone JJ Clin Oncol
- Noble gases identify the mechanisms of fugitive gas contamination in drinking-water wells overlying the Marcellus and Barnett Shales.Darrah TH, Vengosh A, Jackson RB, Warner NR, Poreda RJProc Natl Acad Sci U S A
- Pulque production from fermented agave sap as a dietary supplement in Prehispanic Mesoamerica.Correa-Ascencio M, Robertson IG, Cabrera-Cortés O, Cabrera-Castro R, Evershed RPProc Natl Acad Sci U S A
- A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of 2 Dosing Regimens of Fostamatinib in Patients with Rheumatoid Arthritis with an Inadequate Response to a Tumor Necrosis Factor-α Antagonist.Genovese MC, van der Heijde DM, Keystone E, Spindler AJ, Benhamou C, Kavanaugh A, Fudman E, Lampl K, O'Brien C, Duffield EL, Poiley J, Weinblatt MEJ Rheumatol
- Quality Health Care for Children and the Affordable Care Act: A Voltage Drop Checklist.Cheng TL, Wise PH, Halfon NPediatrics
- Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays.Light JG, Fransen JW, Adekunle AN, Adkins A, Pangeni G, Loudin J, Mathieson K, Palanker DV, McCall MA, Pardue MTExp Eye Res
- Inferior vena cava filters and postoperative outcomes in patients undergoing bariatric surgery: a meta-analysis.Kaw R, Pasupuleti V, Wayne Overby D, Deshpande A, Coleman CI, Ioannidis JP, Hernandez AV, Cardiovascular Meta-analysis Research Group.Surg Obes Relat Dis
- A Systems View of Risk Factors for Knee Osteoarthritis Reveals Insights into the Pathogenesis of the Disease.Andriacchi TP, Favre J, Erhart-Hledik JC, Chu CRAnn Biomed Eng
- The Significance of Atrial Fibrillation in Patients Aged ≥55 years Undergoing Abdominal Surgery.Kazaure HS, Roman SA, Tyler D, Sosa JAWorld J Surg
- Optimizing Adequacy of Bowel Cleansing for Colonoscopy: Recommendations From the US Multi-Society Task Force on Colorectal Cancer.Johnson DA, Barkun AN, Cohen LB, Dominitz JA, Kaltenbach T, Martel M, Robertson DJ, Richard Boland C, Giardello FM, Lieberman DA, Levin TR, Rex DKAm J Gastroenterol
- In response: The RNS System multicenter randomized double-blinded controlled trial of responsive cortical stimulation for adjunctive treatment of intractable partial epilepsy: Knowledge and insights gained.Morrell MJEpilepsia
- Effect of the endothelin type A-selective endothelin receptor antagonist ambrisentan on digital ulcers in patients with systemic sclerosis: results of a prospective pilot study.Chung L, Ball K, Yaqub A, Lingala B, Fiorentino DJ Am Acad Dermatol
- Core content for wilderness medicine fellowship training of emergency medicine graduates.Lipman GS, Weichenthal L, Stuart Harris N, McIntosh SE, Cushing T, Caudell MJ, Macias DJ, Weiss EA, Lemery J, Ellis MA, Spano S, McDevitt M, Tedeschi C, Dow J, Mazzorana V, McGinnis H, Gardner AF, Auerbach PSAcad Emerg Med
- Influence of deforestation, logging, and fire on malaria in the Brazilian Amazon.Hahn MB, Gangnon RE, Barcellos C, Asner GP, Patz JAPLoS One
- Is health aid reaching the poor? Analysis of household data from aid recipient countries.Bendavid EPLoS One
- Optical image-guided cancer therapy.Bu L, Ma X, Tu Y, Shen B, Cheng ZCurr Pharm Biotechnol
- Ultrasound and microbubble guided drug delivery: mechanistic understanding and clinical implications.Tzu-Yin W, Wilson KE, Machtaler S, Willmann JKCurr Pharm Biotechnol
- Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.Dimas AS, Lagou V, Barker A, Knowles JW, Mägi R, Hivert MF, Benazzo A, Rybin D, Jackson AU, Stringham HM, Song C, Fischer-Rosinsky A, Boesgaard TW, Grarup N, Abbasi FA, Assimes TL, Hao K, Yang X, Lecoeur C, Barroso I, Bonnycastle LL, Böttcher Y, Bumpstead S, Chines PS, Erdos MR, Graessler J, Kovacs P, Morken MA, Narisu N, Payne F, Stancakova A, Swift AJ, Tönjes A, Bornstein SR, Cauchi S, Froguel P, Meyre D, Schwarz PE, Häring HU, Smith U, Boehnke M, Bergman RN, Collins FS, Mohlke KL, Tuomilehto J, Quertemous T, Lind L, Hansen T, Pedersen O, Walker M, Pfeiffer AF, Spranger J, Stumvoll M, Meigs JB, Wareham NJ, Kuusisto J, Laakso M, Langenberg C, Dupuis J, Watanabe RM, Florez JC, Ingelsson E, McCarthy MI, Prokopenko I, MAGIC InvestigatorsDiabetes
- MICA, a gene contributing strong susceptibility to ankylosing spondylitis.Zhou X, Wang J, Zou H, Ward MM, Weisman MH, Espitia MG, Xiao X, Petersdorf E, Mignot E, Martin J, Gensler LS, Scheet P, Reveille JDAnn Rheum Dis
- Association of fine specificity and repertoire expansion of anticitrullinated peptide antibodies with rheumatoid arthritis associated interstitial lung disease.Giles JT, Danoff SK, Sokolove J, Wagner CA, Winchester R, Pappas DA, Siegelman S, Connors G, Robinson WH, Bathon JMAnn Rheum Dis
Centralized Monitoring and Virtual Consultant Models of Tele-ICU Care: A Systematic Review.
Telemed J E Health. 2014 Sep 16;
Authors: Ramnath VR, Ho L, Maggio LA, Khazeni N
Abstract Background: Increasing intensivist shortages and demand coupled with the escalating cost of care have created enthusiasm for intensive care unit (ICU)-based telemedicine ("tele-ICU"). This systematic literature review compares the Centralized Monitoring and Virtual Consultant tele-ICU Models. Materials and Methods: With an experienced medical reference librarian, we identified all language publications addressing the employment and efficacy of the centralized monitoring and virtual consultant tele-ICU systems through PubMed, CINAHL, and Web of Science. We performed quantitative and qualitative reviews of documents regarding financial sustainability, clinical outcomes, and ICU staff workflow and acceptance. Results: Of 1,468 documents identified, 1,371 documents were excluded, with the remaining 91 documents addressing clinical outcomes (46 documents [enhanced guideline compliance, 5; mortality and length of stay, 28; and feasibility, 13]), financial sustainability (9 documents), and ICU staff workflow and acceptance (36 documents). Quantitative review showed that studies evaluating the Centralized Monitoring Model were twice as frequent, with a mean of 4,891 patients in an average of six ICUs; Virtual Consultant Model studies enrolled a mean of 372 patients in an average of one ICU. Ninety-two percent of feasibility studies evaluated the Virtual Consultant Model, of which 50% were in the last 3 years. Qualitative review largely confirmed findings in previous studies of centralized monitoring systems. Both the Centralized Monitoring and Virtual Consultant Models showed clinical practice adherence improvement. Although definitive evaluation was not possible given lack of data, the Virtual Consultant Model generally indicated lean absolute cost profile in contrast to centralized monitoring systems. Conclusions: Compared with the Virtual Consultant tele-ICU Model, studies addressing the Centralized Monitoring Model of tele-ICU care were greater in quantity and sample size, with qualitative conclusions of clinical outcomes, staff satisfaction and workload, and financial sustainability largely consistent with past systematic reviews. Attention should be focused on performing more high-quality studies to allow for equitable comparisons between both models.
PMID: 25226571 [PubMed - as supplied by publisher]
A Rapid and Simple Method for DNA Engineering Using Cycled Ligation Assembly.
PLoS One. 2014;9(9):e107329
Authors: Roth TL, Milenkovic L, Scott MP
DNA assembly techniques have developed rapidly, enabling efficient construction of complex constructs that would be prohibitively difficult using traditional restriction-digest based methods. Most of the recent methods for assembling multiple DNA fragments in vitro suffer from high costs, complex set-ups, and diminishing efficiency when used for more than a few DNA segments. Here we present a cycled ligation-based DNA assembly protocol that is simple, cheap, efficient, and powerful. The method employs a thermostable ligase and short Scaffold Oligonucleotide Connectors (SOCs) that are homologous to the ends and beginnings of two adjacent DNA sequences. These SOCs direct an exponential increase in the amount of correctly assembled product during a reaction that cycles between denaturing and annealing/ligating temperatures. Products of early cycles serve as templates for later cycles, allowing the assembly of many sequences in a single reaction. To demonstrate the method's utility, we directed the assembly of twelve inserts, in one reaction, into a transformable plasmid. All the joints were precise, and assembly was scarless in the sense that no nucleotides were added or missing at junctions. Simple, efficient, and low-cost cycled ligation assemblies will facilitate wider use of complex genetic constructs in biomedical research.
PMID: 25226397 [PubMed - as supplied by publisher]
Influence of a custom made maxillary mouthguardguard guard on gas exchange parameters during incremental exercise in amateur road cyclists.
J Strength Cond Res. 2014 Sep 15;
Authors: Piero M, Simone U, Jonathan M, Maria S, Giulio G, Francesco T, Gabriella C, Laura A, Eva B, Gianni M, Francesco C, Giovanni G
Mouthguards are frequently used for protection purposes, particularly by athletes competing in contact sports. However, there is increasing evidence supporting their use for improving performance. Studies have focused their use in athletes who do not traditionally use mouthguards and who may be looking for a performance edge. The aim of the current study was to evaluate the influence of a custom made mouthguard (PM) on maximal and submaximal physiological parameters related to performance in road cycling.Ten well-trained amateur road cyclists (34 ± 6 years) performed an incremental cardiopulmonary exercise test to exhaustion on a frictional braked cycle ergometer. Work rate (WR), heart rate, oxygen consumption (VO2), carbon dioxide production, and ventilation at the lactate threshold, at the respiratory compensation point (RCP), and at maximal exercise (MAX) were determined in normal conditions (C) and wearing PM. Cycling economy was also evaluated by analyzing the slope of the VO2/WR (ΔVO2/ΔWR, mL/watt/min) relationship during the test.Wearing the PM compared to C resulted in significant increases in WR at RCP (281 ± 32 vs 266 ± 19 watts, P=0.04) and at MAX (353 ± 44 vs 339 ± 38 watts, P=0.004). The PM also resulted in an average 8% lower ΔVO2/ΔWR (9.5 ± 1.1 vs 10.3 ± 1.1 mL/watt/min, P=0.06) but did not significantly modify any of the other measured parameters at LT, RCP and MAX.To the best of our knowledge this study is the first to evaluate the effects of a dentistry-designed mouthguard on physical performance of road cyclists. These results provide support for cyclists to correct jaw posture which may improve their exercise performance.
PMID: 25226314 [PubMed - as supplied by publisher]
Predictive Performance of a Gentamicin Population Pharmacokinetic Model in Neonates Receiving Full-Body Hypothermia.
Ther Drug Monit. 2014 Oct;36(5):584-589
Authors: Sampson MR, Frymoyer A, Rattray B, Cotten CM, Smith PB, Capparelli E, Bonifacio SL, Cohen-Wolkowiez M
BACKGROUND:: Population pharmacokinetic (popPK) models derived from small pharmacokinetics (PK) studies in neonates are often underpowered to detect clinically important characteristics that drive dosing. External validation of such models is crucial. In this study, the predictive performance of a gentamicin popPK model in neonates receiving hypothermia was evaluated.
METHODS:: A previously published gentamicin popPK model was developed in neonates with hypoxic ischemic encephalopathy undergoing hypothermia using a retrospective single-institution (University of California-San Francisco) data set. The predictive performance of this model was evaluated in an external retrospective data set from the University of California-San Francisco (validation A) and another from Duke University (validation B). Both institutions used the same hypothermia protocol and collected similar clinical and PK data. Gentamicin dosing and samples were collected per routine care. Predictive performance was evaluated by quantifying the accuracy and precision of model predictions and using simulation-based diagnostics to detect bias in predictions.
RESULTS:: Forty-one neonates (n = 18 validation A; n = 23 validation B) with median (range) gestational age of 40 weeks (33-42) and birth weight of 3.3 kg (1.9-4.6) and 76 samples (55% troughs, 33% and 28% drawn at 24 and 36 hours after dose, respectively) were analyzed. The model adequately predicted gentamicin concentrations from the same institution (validation A; median average fold error = 1.1 and numerical prediction distribution error P > 0.05) but underpredicted concentrations from the outside institution (validation B; median average fold error = 0.6 and numerical prediction distribution error P < 0.05).
CONCLUSIONS:: The model demonstrated adequate predictive performance for an external data set in the same institution but not from an outside institution. Larger sample sizes, use of data from multiple institutions, and external evaluation in development of popPK models in neonates may improve generalizability of dosing recommendations arising from single-institution studies.
PMID: 25225917 [PubMed - as supplied by publisher]
Centralized Monitoring and Virtual Consultant Models of Tele-ICU Care: A Side-by-Side Review.
Telemed J E Health. 2014 Sep 16;
Authors: Ramnath VR, Khazeni N
Abstract Background: Telemedicine-based "tele-intensive care unit" ("tele-ICU") solutions represent an increasingly popular hospital platform to provide ICU specialist expertise while remaining sensitive to healthcare costs. This side-by-side review directly compares the Centralized Monitoring and Virtual Consultant tele-ICU Models. Materials and Methods: We identified all publications in any language addressing the use and efficacy of centralized monitoring and virtual consultant tele-ICU systems through reviews of the PubMed, CINAHL, and Web of Science Web sites, corporate documents, corporate Internet sites, and discussions with corporate representatives. Of the 1,468 documents identified, 1,371 documents were excluded, with the 91 included documents addressing the following: clinical outcomes, 46 documents (enhanced guideline compliance, 5; mortality and length of stay, 28; and feasibility, 13); financial sustainability, 9 documents; and ICU staff workflow and acceptance, 36 documents. We performed qualitative comparative reviews of documents addressing technology, financial sustainability, clinical outcomes, and ICU staff workflow and acceptance. Results: The Centralized Monitoring tele-ICU Model showed improved mortality and/or length of stay and staff acceptance, particularly in rural or specific patient populations, likely because of the presence of integrated clinical information systems and analytics. However, there are high costs and unclear savings. The Virtual Consultant Model could not be adequately evaluated for effects on clinical outcomes or staff acceptance given minimal data. This model can be both portable and implemented at a lower cost profile but cannot integrate different data streams. Improved compliance with clinical practice guidelines was seen in both models. Conclusions: Further study is required to adequately compare these tele-ICU models with regard to clinical outcomes and financial sustainability. With respect to tele-ICU effects on mortality and length of stay improvements and on-site staff acceptance, existing evidence favors the Centralized Monitoring Model. Studies addressing the Virtual Consultant Model are growing in number and are necessary before proper comparisons can be made.
PMID: 25225795 [PubMed - as supplied by publisher]
Cellulose Nanoparticles are a Biodegradable Photoacoustic Contrast Agent for Use in Living Mice.
Photoacoustics. 2014 Sep 1;2(3):119-127
Authors: Jokerst JV, Van de Sompel D, Bohndiek SE, Gambhir SS
Molecular imaging with photoacoustic ultrasound is an emerging field that combines the spatial and temporal resolution of ultrasound with the contrast of optical imaging. However, there are few imaging agents that offer both high signal intensity and biodegradation into small molecules. Here we describe a cellulose-based nanoparticle with peak photoacoustic signal at 700 nm and an in vitro limit of detection of 6 pM (0.02 mg/mL). Doses down to 0.35 nM (1.2 mg/mL) were used to image mouse models of ovarian cancer. Most importantly, the nanoparticles were shown to biodegrade in the presence of cellulase both through a glucose assay and electron microscopy.
PMID: 25225633 [PubMed - as supplied by publisher]
Aesthetic Surgery Training during Residency in the United States: A Comparison of the Integrated, Combined, and Independent Training Models.
Plast Surg Int. 2014;2014:281923
Authors: Momeni A, Kim RY, Wan DC, Izadpanah A, Lee GK
Background. Three educational models for plastic surgery training exist in the United States, the integrated, combined, and independent model. The present study is a comparative analysis of aesthetic surgery training, to assess whether one model is particularly suitable to provide for high-quality training in aesthetic surgery. Methods. An 18-item online survey was developed to assess residents' perceptions regarding the quality of training in aesthetic surgery in the US. The survey had three distinct sections: demographic information, current state of aesthetic surgery training, and residents' perception regarding the quality of aesthetic surgery training. Results. A total of 86 senior plastic surgery residents completed the survey. Twenty-three, 24, and 39 residents were in integrated, combined, and independent residency programs, respectively. No statistically significant differences were seen with respect to number of aesthetic surgery procedures performed, additional training received in minimal-invasive cosmetic procedures, median level of confidence with index cosmetic surgery procedures, or perceived quality of aesthetic surgery training. Facial aesthetic procedures were felt to be the most challenging procedures. Exposure to minimally invasive aesthetic procedures was limited. Conclusion. While the educational experience in aesthetic surgery appears to be similar, weaknesses still exist with respect to training in minimally invasive/nonsurgical aesthetic procedures.
PMID: 25225615 [PubMed]
Computational modeling of skin: Using stress profiles as predictor for tissue necrosis in reconstructive surgery.
Comput Struct. 2014 Sep 1;143:32-39
Authors: Tepole AB, Gosain AK, Kuhl E
Local skin flaps have revolutionized reconstructive surgery. Mechanical loading is critical for flap survival: Excessive tissue tension reduces blood supply and induces tissue necrosis. However, skin flaps have never been analyzed mechanically. Here we explore the stress profiles of two common flap designs, direct advancement flaps and double back-cut flaps. Our simulations predict a direct correlation between regions of maximum stress and tissue necrosis. This suggests that elevated stress could serve as predictor for flap failure. Our model is a promising step towards computer-guided reconstructive surgery with the goal to minimize stress, accelerate healing, minimize scarring, and optimize tissue use.
PMID: 25225454 [PubMed - as supplied by publisher]
Development and Future of the American Society of Clinical Oncology's Quality Oncology Practice Initiative.
J Clin Oncol. 2014 Sep 15;
Authors: Blayney DW, McNiff K, Eisenberg PD, Gilmore T, Jacobsen PB, Jacobson JO, Kadlubek PJ, Neuss MN, Simone J
PMID: 25225418 [PubMed - as supplied by publisher]
Noble gases identify the mechanisms of fugitive gas contamination in drinking-water wells overlying the Marcellus and Barnett Shales.
Proc Natl Acad Sci U S A. 2014 Sep 15;
Authors: Darrah TH, Vengosh A, Jackson RB, Warner NR, Poreda RJ
Horizontal drilling and hydraulic fracturing have enhanced energy production but raised concerns about drinking-water contamination and other environmental impacts. Identifying the sources and mechanisms of contamination can help improve the environmental and economic sustainability of shale-gas extraction. We analyzed 113 and 20 samples from drinking-water wells overlying the Marcellus and Barnett Shales, respectively, examining hydrocarbon abundance and isotopic compositions (e.g., C2H6/CH4, δ(13)C-CH4) and providing, to our knowledge, the first comprehensive analyses of noble gases and their isotopes (e.g., (4)He, (20)Ne, (36)Ar) in groundwater near shale-gas wells. We addressed two questions. (i) Are elevated levels of hydrocarbon gases in drinking-water aquifers near gas wells natural or anthropogenic? (ii) If fugitive gas contamination exists, what mechanisms cause it? Against a backdrop of naturally occurring salt- and gas-rich groundwater, we identified eight discrete clusters of fugitive gas contamination, seven in Pennsylvania and one in Texas that showed increased contamination through time. Where fugitive gas contamination occurred, the relative proportions of thermogenic hydrocarbon gas (e.g., CH4, (4)He) were significantly higher (P < 0.01) and the proportions of atmospheric gases (air-saturated water; e.g., N2, (36)Ar) were significantly lower (P < 0.01) relative to background groundwater. Noble gas isotope and hydrocarbon data link four contamination clusters to gas leakage from intermediate-depth strata through failures of annulus cement, three to target production gases that seem to implicate faulty production casings, and one to an underground gas well failure. Noble gas data appear to rule out gas contamination by upward migration from depth through overlying geological strata triggered by horizontal drilling or hydraulic fracturing.
PMID: 25225410 [PubMed - as supplied by publisher]
Pulque production from fermented agave sap as a dietary supplement in Prehispanic Mesoamerica.
Proc Natl Acad Sci U S A. 2014 Sep 15;
Authors: Correa-Ascencio M, Robertson IG, Cabrera-Cortés O, Cabrera-Castro R, Evershed RP
Although in modern societies fermented beverages are associated with socializing, celebration, and ritual, in ancient times they were also important sources of essential nutrients and potable water. In Mesoamerica, pulque, an alcoholic beverage produced from the fermented sap of several species of maguey plants (Agavaceae; Fig. 1) is hypothesized to have been used as a dietary supplement and risk-buffering food in ancient Teotihuacan (150 B.C. to A.D. 650). Although direct archaeological evidence of pulque production is lacking, organic residue analysis of pottery vessels offers a new avenue of investigation. However, the chemical components of alcoholic beverages are water-soluble, greatly limiting their survival over archaeological timescales compared with hydrophobic lipids widely preserved in food residues. Hence, we apply a novel lipid biomarker approach that considers detection of bacteriohopanoids derived from the ethanol-producing bacterium Zymomonas mobilis for identifying pulque production/consumption in pottery vessels. Gas chromatography-mass spectrometry selected ion monitoring (m/z 191) of lipid extracts of >300 potsherds revealed characteristic bacteriohopanoid distributions in a subset of 14 potsherds. This hopanoid biomarker approach offers a new means of identifying commonly occurring bacterially fermented alcoholic beverages worldwide, including palm wine, beer, cider, perry, and other plant sap- or fruit-derived beverages [Swings J, De Ley J (1977) Bacteriol Rev 41(1):1-46].
PMID: 25225408 [PubMed - as supplied by publisher]
A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of 2 Dosing Regimens of Fostamatinib in Patients with Rheumatoid Arthritis with an Inadequate Response to a Tumor Necrosis Factor-α Antagonist.
J Rheumatol. 2014 Sep 15;
Authors: Genovese MC, van der Heijde DM, Keystone E, Spindler AJ, Benhamou C, Kavanaugh A, Fudman E, Lampl K, O'Brien C, Duffield EL, Poiley J, Weinblatt ME
OBJECTIVE: Our 24-week study (NCT01197755; OSKIRA-3) compared the efficacy and safety of fostamatinib versus placebo in patients taking background methotrexate treatment with active rheumatoid arthritis (RA) and an inadequate response to a single tumor necrosis factor-α antagonist.
METHODS: Adult patients were randomized (1:1:1) to fostamatinib [100 mg bid for 24 weeks (n = 105; Group A)], or 100 mg bid for 4 weeks, then 150 mg qd (n = 108; Group B), or to placebo (n = 110; Group C) for 24 weeks. Nonresponders at Week 12 could enter a longterm extension study. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at Week 24.
RESULTS: Baseline characteristics were well balanced. Significantly more patients in fostamatinib Group A (36.2%; p = 0.004), but not B (27.8%; p = 0.168), achieved ACR20 at Week 24 versus placebo (21.1%). Frequently reported adverse events were diarrhea, hypertension, and headache. Elevated blood pressure (≥ 140/90 mm Hg) at ≥ 1 visit was observed in 46.7%, 51.9%, and 26.6% of patients, respectively. There were 2 deaths in the study, 1 in Group B and 1 in the placebo group.
CONCLUSION: Fostamatinib 100 mg bid, but not fostamatinib 100 mg bid for 4 weeks then 150 mg qd, achieved statistical improvements in ACR20 at 24 weeks versus placebo. Because of efficacy and safety results from the phase III clinical program, the companies developing fostamatinib have decided not to study it further in RA at this time.
PMID: 25225285 [PubMed - as supplied by publisher]
Quality Health Care for Children and the Affordable Care Act: A Voltage Drop Checklist.
Pediatrics. 2014 Sep 15;
Authors: Cheng TL, Wise PH, Halfon N
The Affordable Care Act (ACA) introduces enormous policy changes to the health care system with several anticipated benefits and a growing number of unanticipated challenges for child and adolescent health. Because the ACA gives each state and their payers substantial autonomy and discretion on implementation, understanding potential effects will require state-by-state monitoring of policies and their impact on children. The "voltage drop" framework is a useful interpretive guide for assessing the impact of insurance market change on the quality of care received. Using this framework we suggest a state-level checklist to examine ACA statewide implementation, assess its impact on health care delivery, and frame policy correctives to improve child health system performance. Although children's health care is a small part of US health care spending, child health provides the foundation for adult health and must be protected in ACA implementation.
PMID: 25225140 [PubMed - as supplied by publisher]
Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays.
Exp Eye Res. 2014 Sep 12;
Authors: Light JG, Fransen JW, Adekunle AN, Adkins A, Pangeni G, Loudin J, Mathieson K, Palanker DV, McCall MA, Pardue MT
Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6 to 12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16 to 26 weeks post implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission.
PMID: 25224340 [PubMed - as supplied by publisher]
Inferior vena cava filters and postoperative outcomes in patients undergoing bariatric surgery: a meta-analysis.
Surg Obes Relat Dis. 2014 July - August;10(4):725-733
Authors: Kaw R, Pasupuleti V, Wayne Overby D, Deshpande A, Coleman CI, Ioannidis JP, Hernandez AV, Cardiovascular Meta-analysis Research Group.
PMID: 25224168 [PubMed - as supplied by publisher]
A Systems View of Risk Factors for Knee Osteoarthritis Reveals Insights into the Pathogenesis of the Disease.
Ann Biomed Eng. 2014 Sep 16;
Authors: Andriacchi TP, Favre J, Erhart-Hledik JC, Chu CR
Early detection of osteoarthritis (OA) remains a critical yet unsolved multifaceted problem. To address the multifaceted nature of OA a systems model was developed to consolidate a number of observations on the biological, mechanical and structural components of OA and identify features common to the primary risk factors for OA (aging, obesity and joint trauma) that are present prior to the development of clinical OA. This analysis supports a unified view of the pathogenesis of OA such that the risk for developing OA emerges when one of the components of the disease (e.g., mechanical) becomes abnormal, and it is the interaction with the other components (e.g., biological and/or structural) that influences the ultimate convergence to cartilage breakdown and progression to clinical OA. The model, applied in a stimulus-response format, demonstrated that a mechanical stimulus at baseline can enhance the sensitivity of a biomarker to predict cartilage thinning in a 5 year follow-up in patients with knee OA. The systems approach provides new insight into the pathogenesis of the disease and offers the basis for developing multidisciplinary studies to address early detection and treatment at a stage in the disease where disease modification has the greatest potential for a successful outcome.
PMID: 25224078 [PubMed - as supplied by publisher]
The Significance of Atrial Fibrillation in Patients Aged ≥55 years Undergoing Abdominal Surgery.
World J Surg. 2014 Sep 16;
Authors: Kazaure HS, Roman SA, Tyler D, Sosa JA
BACKGROUND: The Institute of Medicine has identified atrial fibrillation (AF) among national priorities for research. We examine the incidence of AF and its association with outcomes of patients undergoing abdominal surgery.
METHODS: Patients ≥55 years who underwent abdominal surgery captured in a State Inpatient Database, 2008-2010. Three patient groups were created: (1) No diagnosis of AF (No-AF), (2) Pre-existing AF (Hx-AF), and (3) New-onset AF (New-AF). Outcomes were analysed using bivariate and multivariate methods.
RESULTS: AF incidence among 116,477 patients was 8.6 %; approximately one in four patients aged ≥85 years had AF. 26.6 % of patients with AF experienced New-AF; the latter was more likely after pancreas resection (43.0 %) and least common after cholecystectomy (20.2 %). Complications (71.1, 47.3 vs. 26.5 %), mortality (8.0, 5.7 vs. 2.0 %), longer hospital stays (8.8, 5.6 vs. 3.8 days), and higher hospitalization cost ($41,427, $26,312 vs. $18,310) were more likely in patients with AF (New-AF, Hx-AF vs. No-AF respectively) (all p < 0.001). After adjustment, New-AF was among factors independently associated with mortality (OR 2.0, 95 % CI 1.7-2.4, p < 0.001); each case of New-AF increased cost of care by $4,482. Factors independently associated with New-AF included ≥1 complication, electrolyte imbalance, and procedure-type. Whereas 2.0 % of patients who developed New-AF were admitted from a long-term care facility, 23.8 % of patients with New-AF were discharged to a long-term care facility.
CONCLUSIONS: AF is common among abdominal surgery patients, particularly the elderly; New-AF is a serious, potentially avoidable adverse event that could serve as an important quality of care indicator for abdominal surgery patients.
PMID: 25223740 [PubMed - as supplied by publisher]
Optimizing Adequacy of Bowel Cleansing for Colonoscopy: Recommendations From the US Multi-Society Task Force on Colorectal Cancer.
Am J Gastroenterol. 2014 Sep 16;
Authors: Johnson DA, Barkun AN, Cohen LB, Dominitz JA, Kaltenbach T, Martel M, Robertson DJ, Richard Boland C, Giardello FM, Lieberman DA, Levin TR, Rex DK
PMID: 25223578 [PubMed - as supplied by publisher]
In response: The RNS System multicenter randomized double-blinded controlled trial of responsive cortical stimulation for adjunctive treatment of intractable partial epilepsy: Knowledge and insights gained.
Epilepsia. 2014 Sep;55(9):1470-1
Authors: Morrell MJ
PMID: 25223509 [PubMed - in process]
Effect of the endothelin type A-selective endothelin receptor antagonist ambrisentan on digital ulcers in patients with systemic sclerosis: results of a prospective pilot study.
J Am Acad Dermatol. 2014 Aug;71(2):400-1
Authors: Chung L, Ball K, Yaqub A, Lingala B, Fiorentino D
PMID: 25037794 [PubMed - indexed for MEDLINE]
Core content for wilderness medicine fellowship training of emergency medicine graduates.
Acad Emerg Med. 2014 Feb;21(2):204-7
Authors: Lipman GS, Weichenthal L, Stuart Harris N, McIntosh SE, Cushing T, Caudell MJ, Macias DJ, Weiss EA, Lemery J, Ellis MA, Spano S, McDevitt M, Tedeschi C, Dow J, Mazzorana V, McGinnis H, Gardner AF, Auerbach PS
Wilderness medicine is the practice of resource-limited medicine under austere conditions. In 2003, the first wilderness medicine fellowship was established, and as of March 2013, a total of 12 wilderness medicine fellowships exist. In 2009 the American College of Emergency Physicians Wilderness Medicine Section created a Fellowship Subcommittee and Taskforce to bring together fellowship directors, associate directors, and other interested stakeholders to research and develop a standardized curriculum and core content for emergency medicine (EM)-based wilderness medicine fellowships. This paper describes the process and results of what became a 4-year project to articulate a standardized curriculum for wilderness medicine fellowships. The final product specifies the minimum core content that should be covered during a 1-year wilderness medicine fellowship. It also describes the structure, length, site, and program requirements for a wilderness medicine fellowship.
PMID: 24438590 [PubMed - indexed for MEDLINE]
Influence of deforestation, logging, and fire on malaria in the Brazilian Amazon.
PLoS One. 2014;9(1):e85725
Authors: Hahn MB, Gangnon RE, Barcellos C, Asner GP, Patz JA
Malaria is a significant public health threat in the Brazilian Amazon. Previous research has shown that deforestation creates breeding sites for the main malaria vector in Brazil, Anopheles darlingi, but the influence of selective logging, forest fires, and road construction on malaria risk has not been assessed. To understand these impacts, we constructed a negative binomial model of malaria counts at the municipality level controlling for human population and social and environmental risk factors. Both paved and unpaved roadways and fire zones in a municipality increased malaria risk. Within the timber production states where 90% of deforestation has occurred, compared with areas without selective logging, municipalities where 0-7% of the remaining forests were selectively logged had the highest malaria risk (1.72, 95% CI 1.18-2.51), and areas with higher rates of selective logging had the lowest risk (0.39, 95% CI 0.23-0.67). We show that roads, forest fires, and selective logging are previously unrecognized risk factors for malaria in the Brazilian Amazon and highlight the need for regulation and monitoring of sub-canopy forest disturbance.
PMID: 24404206 [PubMed - indexed for MEDLINE]
Is health aid reaching the poor? Analysis of household data from aid recipient countries.
PLoS One. 2014;9(1):e84025
Authors: Bendavid E
OBJECTIVE: To determine the extent to which the narrowing of child mortality across wealth gradients has been related to foreign aid to the health sector in low- and middle-income countries.
METHODS: Mortality and wealth data on 989,901 under-5 children from 957,674 households in 49 aid recipient countries in Africa, Asia, South America, and the Caribbean between 1993 and 2012 were used in the analysis. Declines in under-5 mortality in the four poorest wealth quantiles were compared to the decline among the wealthiest at varying levels of health aid per capita using fixed effects multivariable regression models and controlling for maternal education, urbanization, and domestic spending on health among recipient countries.
RESULTS: Each additional dollar in total health aid per capita was associated with 5.7 fewer deaths per 10,000 child-years among children in the poorest relative to the wealthiest households (p<0.001). This was also true when measured in percent declines (1.90% faster decline in under-5 mortality among the poorest compared with the wealthiest with each dollar in total health aid, p = 0.008). The association was stronger when using health aid specifically for malaria than total health aid, 12.60% faster decline among the poorest compared with the wealthiest with each dollar in malaria aid, p = 0.001.
CONCLUSIONS: Foreign aid to the health sector is preferentially related to reductions in under-5 mortality among the poorest compared with the wealthiest. Health aid addressing malaria, which imposes a disproportionate burden among the poor, may explain the observed effect.
PMID: 24404148 [PubMed - indexed for MEDLINE]
Optical image-guided cancer therapy.
Curr Pharm Biotechnol. 2014 Oct;14(8):723-32
Authors: Bu L, Ma X, Tu Y, Shen B, Cheng Z
Optical molecular imaging holds great promise for image guiding cancer therapy. The non-invasive guidance of therapeutic strategies would enable the removal of cancerous tissue while avoiding side effects and systemic toxicity, preventing damage of healthy tissues and decreasing the risk of postoperative problems. This review article highlights the advantages and disadvantages of the optical imaging techniques that are currently available, including their recent applications in image-guided cancer therapy. Three approaches for optical image-guided cancer therapy were discussed in this review, namely, bioluminescence imaging (BLI), fluorescence imaging (FI) and Cerenkov luminescence imaging (CLI). BLI is always used in small animal imaging for the in vivo tracking of therapeutic gene expression and cell-based therapy. To the contrary, FI display high promising for clinical translation. The applications of FI include image-guided surgery, radiotherapy, gene therapy, drug delivery and sentinel lymph node fluorescence mapping. CLI is a novel radioactive optical hybrid imaging strategy and its use for animal and clinical translation was also discussed. Perspectives on the translation of optical image-guided cancer therapy into clinical practice were provided.
PMID: 24372233 [PubMed - indexed for MEDLINE]
Ultrasound and microbubble guided drug delivery: mechanistic understanding and clinical implications.
Curr Pharm Biotechnol. 2014 Oct;14(8):743-52
Authors: Tzu-Yin W, Wilson KE, Machtaler S, Willmann JK
Ultrasound mediated drug delivery using microbubbles is a safe and noninvasive approach for spatially localized drug administration. This approach can create temporary and reversible openings on cellular membranes and vessel walls (a process called "sonoporation"), allowing for enhanced transport of therapeutic agents across these natural barriers. It is generally believed that the sonoporation process is highly associated with the energetic cavitation activities (volumetric expansion, contraction, fragmentation, and collapse) of the microbubble. However, a thorough understanding of the process was unavailable until recently. Important progress on the mechanistic understanding of sonoporation and the corresponding physiological responses in vitro and in vivo has been made. Specifically, recent research shed light on the cavitation process of microbubbles and fluid motion during insonation of ultrasound, on the spatio-temporal interactions between microbubbles and cells or vessel walls, as well as on the temporal course of the subsequent biological effects. These findings have significant clinical implications on the development of optimal treatment strategies for effective drug delivery. In this article, current progress in the mechanistic understanding of ultrasound and microbubble mediated drug delivery and its implications for clinical translation is discussed.
PMID: 24372231 [PubMed - indexed for MEDLINE]
Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.
Diabetes. 2014 Jun;63(6):2158-71
Authors: Dimas AS, Lagou V, Barker A, Knowles JW, Mägi R, Hivert MF, Benazzo A, Rybin D, Jackson AU, Stringham HM, Song C, Fischer-Rosinsky A, Boesgaard TW, Grarup N, Abbasi FA, Assimes TL, Hao K, Yang X, Lecoeur C, Barroso I, Bonnycastle LL, Böttcher Y, Bumpstead S, Chines PS, Erdos MR, Graessler J, Kovacs P, Morken MA, Narisu N, Payne F, Stancakova A, Swift AJ, Tönjes A, Bornstein SR, Cauchi S, Froguel P, Meyre D, Schwarz PE, Häring HU, Smith U, Boehnke M, Bergman RN, Collins FS, Mohlke KL, Tuomilehto J, Quertemous T, Lind L, Hansen T, Pedersen O, Walker M, Pfeiffer AF, Spranger J, Stumvoll M, Meigs JB, Wareham NJ, Kuusisto J, Laakso M, Langenberg C, Dupuis J, Watanabe RM, Florez JC, Ingelsson E, McCarthy MI, Prokopenko I, MAGIC Investigators
Patients with established type 2 diabetes display both β-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.
PMID: 24296717 [PubMed - indexed for MEDLINE]
MICA, a gene contributing strong susceptibility to ankylosing spondylitis.
Ann Rheum Dis. 2014 Aug;73(8):1552-7
Authors: Zhou X, Wang J, Zou H, Ward MM, Weisman MH, Espitia MG, Xiao X, Petersdorf E, Mignot E, Martin J, Gensler LS, Scheet P, Reveille JD
OBJECTIVE: The human major histocompatibility complex class I chain-related gene A (MICA) controls the immune process by balancing activities of natural killer cells, γδ T cells and αβ CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide association studies indicate that genes most strongly linked to ankylosing spondylitis (AS) susceptibility come from the region containing HLA-B and MICA. While HLA-B27 is a well-known risk genetic marker for AS, the potential effect of linkage disequilibrium (LD) shields any associations of genes around HLA-B with AS. The aim of this study was to investigate a novel independent genetic association of MICA to AS.
METHODS: We examined 1543 AS patients and 1539 controls from two ethnic populations by sequencing MICA and genotyping HLA-B alleles. Initially, 1070 AS patients and 1003 controls of European ancestry were used as a discovery cohort, followed by a confirmation cohort of 473 Han Chinese AS patients and 536 controls. We performed a stratified analysis based on HLA-B27 carrier status. We also conducted logistic regression with a formal interaction term.
RESULTS: Sequencing of MICA identified that MICA*007:01 is a significant risk allele for AS in both Caucasian and Han Chinese populations, and that MICA*019 is a major risk allele in Chinese AS patients. Conditional analysis of MICA alleles on HLA-B27 that unshielded LD effect confirmed associations of the MICA alleles with AS.
CONCLUSIONS: Parallel with HLA-B27, MICA confers strong susceptibility to AS in US white and Han Chinese populations.
PMID: 23727634 [PubMed - indexed for MEDLINE]
Association of fine specificity and repertoire expansion of anticitrullinated peptide antibodies with rheumatoid arthritis associated interstitial lung disease.
Ann Rheum Dis. 2014 Aug;73(8):1487-94
Authors: Giles JT, Danoff SK, Sokolove J, Wagner CA, Winchester R, Pappas DA, Siegelman S, Connors G, Robinson WH, Bathon JM
BACKGROUND: Interstitial lung disease (ILD) is associated with high morbidity and mortality in rheumatoid arthritis (RA). Citrullinated proteins are observed in RA lung tissues; however, the association of specific anticitrullinated peptide antibodies (ACPA) with ILD in RA is unknown.
METHODS: RA patients underwent multidetector CT (MDCT) of the chest, from which ILD features and a semiquantitative ILD Score (ILDS; range 0-32) were assessed. Anti-CCP (CCP2) and levels of a panel of antibodies against 17 citrullinated and four non-citrullinated peptides were assessed from concurrent serum samples using a custom Bio-Plex bead array. High level ACPA was defined as ≥the group 75th percentile.
RESULTS: Among the 177 RA patients studied, median levels of CCP2 and all specific ACPAs were 46-273% higher among RA patients with versus those without ILD (all p values <0.05), and higher levels correlated with higher ILDS. In contrast, levels of non-citrullinated protein antibodies were not higher in those with ILD. RA patients had a median of 2 high level ACPA reactivities (range 0-16), with each high level ACPA associated, on average, with a 0.10 unit higher ILDS (p=0.001). This association remained significant after adjusting for characteristics associated with ILD (age, gender, current and former smoking, Disease Activity Score for 28 joints, current prednisone and leflunomide use). More high level ACPA were observed in those with versus without pulmonary function restriction or impaired diffusion.
CONCLUSIONS: Our findings of a broader ACPA repertoire in RA ILD suggest a possible role for ACPA in the pathogenesis of ILD.
PMID: 23716070 [PubMed - indexed for MEDLINE]
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