To determine the rates at which private primary-care clinics are recommending blood pressure and cholesterol measurement, smoking cessation, clinical breast examination, screening mammography, ...Papanicolaou testing, and influenza and pneumococcus immunizations.
We conducted a mail survey of 7,997 randomly selected patients from 44 primary-care clinics in and around Minneapolis-St. Paul, Minnesota, of whom 6,830 (85.4%) completed the questionnaire on preventive services delivery rates. The responses were analyzed statistically, including stratification by reason for the clinic visit.
On the average, about two-thirds of the patients in each clinic reported being up-to-date on preventive services before their clinic visit; an exception was pneumococcus immunization (mean rate, 33%). Except for blood pressure and smoking cessation advice, less than 30% of patients who were not up-to-date on a preventive service were offered it if the clinic visit was for a reason other than a checkup or physical examination. For patients who said that they saw their physician for a checkup or physical examination, the rate was more than 50% only for Papanicolaou smear. In contrast, nearly all responding practitioners agreed that each of the eight preventive services was very important or important.
Preventive services consensus goals are not being met, even for patients who report that their clinic visit was for a checkup or physical examination. This finding suggests that it may be necessary to develop clinical systems that support and enable the delivery of preventive services.
Meta-analysis was used to examine 108 intervention comparisons in 39 controlled smoking cessation trials. Type of intervention (face-to-face advice being better than all others), type of intervenor ...(both physician and nonphysician counselors better than either alone), the number of reinforcing sessions, and the duration of reinforcing sessions were related to success six months after the initiation of intervention. The number of modalities used by the intervention predicted success with borderline statistical significance. Multivariate analysis predicted that a team of physicians and nonphysicians using multiple intervention modalities to deliver individualized advice on multiple occasions would produce the best result. Program success 12 months after the initiation of intervention was related to the type of intervention session (group and individual sessions combined better than either alone), the number of intervention modalities, and the number of reinforcing sessions. With multivariate adjustment for confounding, the number of intervention modalities alone had a positive association with intervention success.
Summary Both the complement system and tissue factor (TF), a key initiating component of coagulation, are activated in sepsis, and cross-talk occurs between the complement and coagulation systems. ...C1-inhibitor (C1-INH) can act as a regulator in both systems. Our aim in this study was to examine this cross-talk by investigating the effects of C1-INH on Escherichia coli-induced haemostasis and inflammation. Fresh human whole blood collected in lepirudin was incubated with E.coli or ultrapurified E.coli lipopolysaccharide (LPS) in the absence or presence of C1-INH or protease-inactivated C1-INH. C3 activation was blocked by compstatin, a specific C3 convertase inhibitor. TF mRNA was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and TF surface expression was measured by flow cytometry. In plasma, the terminal complement complex, prothrombin F1·2 (PTF1·2) and long pentraxin 3 (PTX3) were measured by enzyme-linked immunosorbent assay (ELISA). Cytokines were analysed using a multiplex kit. C1-INH (1·25-5mg/ml) reduced both LPS- and E.coli-induced coagulation, measured as a reduction of PTF1·2 in plasma, efficiently and dose-dependently (P<0·05). Both LPS and E.coli induced marked up-regulation of TF mRNA levels and surface expression on whole blood monocytes. This up-regulation was reduced efficiently by treatment with C1-INH (P<0·05). C1-INH reduced the release of PTX3 (P<0·05) and virtually all cytokines measured (P<0·05). Complement activation was inhibited more efficiently with compstatin than with C1-INH. C1-INH inhibited most of the other readouts more efficiently, consistent with additional non-complement-dependent effects. These results indicate that complement plays a role in activating coagulation during sepsis and that C1-INH is a broad-spectrum attenuator of the inflammatory and haemostatic responses. PUBLICATION ABSTRACT
Intensification, the process of intensifying land management to enhance agricultural goods, results in “intensive” pastures that are planted with productive grasses and fertilized. These intensive ...pastures provide essential ecosystem services, including forage production for livestock. Understanding the synergies and tradeoffs of pasture intensification on the delivery of services across climatic regions is crucial to shape policies and incentives for better management of natural resources. Here, we investigated how grassland intensification affects key components of provisioning (forage productivity and quality), supporting (plant diversity) and regulating services (CO2 and CH4 fluxes) by comparing these services between intensive versus extensive pastures in subtropical and temperate pastures in the USDA Long-term Agroecosystem Research (LTAR) Network sites in Florida and Oklahoma, USA over multiple years. Our results suggest that grassland intensification led to a decrease in measured supporting and regulating services, but increased forage productivity in temperate pastures and forage digestibility in subtropical pastures. Intensification decreased the net CO2 sink of subtropical pastures while it did not affect the sink capacity of temperate pastures; and it also increased environmental CH4 emissions from subtropical pastures and reduced CH4 uptake in temperate pastures. Intensification enhanced the global warming potential associated with C fluxes of pastures in both ecoregions. Our study demonstrates that comparisons of agroecosystems in contrasting ecoregions can reveal important drivers of ecosystem services and general or region-specific opportunities and solutions to maintaining agricultural production and reducing environmental footprints. Further LTAR network-scale comparisons of multiple ecosystem services across croplands and grazinglands intensively vs extensively managed are warranted to inform the sustainable intensification of agriculture within US and beyond. Our results highlight that achieving both food security and environmental stewardship will involve the conservation of less intensively managed pastures while adopting sustainable strategies in intensively managed pastures.
•Intensification did not increase forage productivity in subtropical pastures.•Intensification increased forage productivity in temperate pastures.•Intensification reduced supporting and regulating services in pastures.•Intensification reduced CO2 sink capacity and increased CH4 emissions of subtropical pastures.•Intensification increased the global warming potential associated with C fluxes in pastures.
Background: Sepsis Sepsis is a major world-wide medical problem with high morbidity and mortality. Gram-negative bacteria are among the most important pathogens of sepsis and their LPS LPS content is ...regarded to be important for the systemic inflammatory reaction. The CD14 CD14/myeloid differentiation factor 2 (MD-2 MD-2)/TLR4 complex plays a major role in the immune response to LPS LPS. The aim of this study was to compare the effects of inhibiting MD-2 MD-2 and CD14 CD14 on ultra-pure LPS LPS- versus whole E. coli E. coli bacteria-induced responses. Methods: Fresh human whole blood was incubated with upLPS or whole E. coli E. coli bacteria in the presence of MD-2 MD-2 or CD14 CD14 neutralizing monoclonal antibodies, or their respective controls, and/or the specific complement-inhibitor compstatin. Cytokines Cytokines were measured by a multiplex (n = 27) assay. NFκB activity was examined in cells transfected with CD14 CD14, MD-2 MD-2 and/or Toll-like receptors. Results: LPS LPS-induced cytokine response was efficiently and equally abolished by MD-2 MD-2 and CD14 CD14 neutralization. In contrast, the response induced by whole E. coli E. coli bacteria was only modestly reduced by MD-2 MD-2 neutralization, whereas CD14 CD14 neutralization was more efficient. Combination with compstatin enhanced the effect of MD-2 MD-2 neutralization slightly. When compstatin was combined with CD14 CD14 neutralization, however, the response was virtually abolished for all cytokines, including IL-17, which was only inhibited by this combination. The MD-2 MD-2-independent effect observed for CD14 CD14 could not be explained by TLR2 signaling. Conclusion: Inhibition of CD14 CD14 is more efficient than inhibition of MD-2 MD-2 on whole E. coli E. coli-induced cytokine response, suggesting CD14 CD14 to be a better target for intervention in Gram-negative sepsis, in particular when combined with complement inhibition.
Recombinant tumor necrosis factor alpha (rTNF-alpha)-induced release of endogenous fatty acids was examined in WEHI 164 clone 13 fibrosarcoma cells using a highly sensitive HPLC method. The initial ...rTNF-alpha-induced extracellular release of endogenous fatty acids was dominated by 20:4n;-6, 22:4n;-6, 24:4n;-6, and 18:1n;-9 showing relative rates of 2.9, 0.9, 1.1, and 1.0, respectively. Release of endogenous AA and DNA fragmentation occurred simultaneously and preceded cell death by approx. 2 h. Methyl arachidonoyl fluorophosphonate and LY311727, specific inhibitors of Ca(2+)-dependent cytosolic PLA(2) (cPLA(2)) and secretory PLA(2) (sPLA(2)), respectively, neither blocked rTNF-alpha-induced cytotoxicity or endogenous AA release. However, both inhibitors reduced rTNF-alpha-induced release of other endogenous fatty acids. In comparison, the antioxidant butylated hydroxyanisole (BHA) completely inhibited the rTNF-alpha-induced cytotoxicity as well as AA release mediated through the TNF receptor p55, while the very similar antioxidant butylated hydroxytoluene had no effect. BHA did not inhibit recombinant cPLA(2) or sPLA(2) enzyme activity in vitro. Furthermore, stimulation of cells with rTNF-alpha for 4 h did not increase cPLA(2) enzyme activity. The data indicate that neither cPLA(2) or sPLA(2) mediate rTNF-alpha-induced apoptosis and extracellular AA release in WEHI cells. The results suggest that a BHA-sensitive signaling pathway coupled to AA release is a key event in TNF-induced cytotoxicity in these cells.
C1-inhibitor is increasingly used experimentally and clinically in inflammatory conditions like septicemia and ischemia-reperfusion injury. Several mechanisms may account for the anti-inflammatory ...effects of C1-inhibitor, including inhibition of complement. The aim of the present study was to investigate and compare the supraphysiologic effect of C1-inhibitor on the three complement pathways. Novel assays for specific evaluation of the classical, lectin and alternative pathways were employed using normal human serum supplemented with increasing concentrations of C1-inhibitor. Solid-phase classical- and lectin pathway activation was dose-dependently and significantly reduced up to 85% in the range of 2–28 times physiologic C1-inhibitor concentration. The lectin pathway was more potently inhibited than the classical at low doses. A functional lectin pathway assay demonstrated a significant reduction of C4 deposition up to 86% even at low concentration of C1-inhibitor and documented the effect to be at the level of MBL/MASPs. In contrast, C1-inhibitor had no effect on solid-phase alternative pathway activation, but significantly reduced cobra venom factor-induced fluid-phase activation up to 88%. The negative controls albumin and IgG had no effect on complement activation. The positive inhibitory controls compstatin (C3 inhibition), EDTA- or MBL-deficient sera reduced complement activation by 82–100%. We conclude that C1-inhibitor in high physiologic doses differentially inhibits all three-complement pathways. The inhibition pattern was strikingly different in the classical and lectin pathway, compared to the alternative. Previous studies interpreting the effects of C1-inhibitor as only due to classical pathway inhibition needs reconsideration. The data has implications for the therapeutic use of C1-inhibitor.
OBJECTIVES: The transition from ICD-9-CM to ICD-10-CM in October 2015 raised potential concerns due to differences in diagnosis code specificity across some conditions. Counts and percentages of ...patients with each of nine conditions in September 2015, October 2015, and October 2016 were compared in a large US managed care database. METHODS: This retrospective analysis used medical claims data for commercial and Medicare Advantage enrollees in September 2015, October 2015, and October 2016. Patients with > 1 medical claim for type 2 diabetes mellitus (T2DM), depression, lung cancer, rheumatoid arthritis (RA), atherosclerotic cardiovascular disease (ASCVD), chronic obstructive pulmonary disease (COPD), hepatitis C, asthma, or heart failure were retained. ICD-9-CM and ICD-10-CM code lists were constructed by an MD coding specialist. Monthly patient counts for each condition were determined and the percentage of patients with each condition was calculated relative to the entire database. RESULTS: In 2015 and 2016, data were available for 12.45 million and 13.84 million patients, respectively. For 6 of the 9 conditions, the absolute percentage of patients increased after one year (September 2015, October 2015, October 2016): T2DM, 3.15%, 3.11%, 3.47%; depression, 2.00%, 1.86%, 1.89%; lung cancer, 0.11%, 0.11%, 0.12%; RA, 0.26%, 0.26%, 0.27%; ASCVD, 1.18%, 1.68%, 1.84%; COPD, 1.13%, 1.15%, 1.30%; hepatitis C, 0.08%, 0.08%, 0.07%; asthma, 0.87%, 0.82%, 0.85%; heart failure, 0.57%, 0.58%, 0.66%. Possible reasons for these variations included differences in code representations and the use of generalized codes early in the transition. CONCLUSIONS: In this large US managed care database analysis, the transition from ICD-9-CM to ICD-10-CM codes was associated with absolute percentage increases in 6 of 9 conditions after one year, requiring further analysis of the reasons for these increases. These findings indicate the importance of careful review of code lists for analyses bridging the transition period and the need for investigation of the reasons for inconsistencies.
For much of the last century, forecasting centers around the world have offered seasonal streamflow predictions to support water management. Recent work suggests that the two major avenues to advance ...seasonal predictability are improvements in the estimation of initial hydrologic conditions (IHCs) and the incorporation of climate information. This study investigates the marginal benefits of a variety of methods using IHCs and/or climate information, focusing on seasonal water supply forecasts (WSFs) in five case study watersheds located in the US Pacific Northwest region. We specify two benchmark methods that mimic standard operational approaches – statistical regression against IHCs and model-based ensemble streamflow prediction (ESP) – and then systematically intercompare WSFs across a range of lead times. Additional methods include (i) statistical techniques using climate information either from standard indices or from climate reanalysis variables and (ii) several hybrid/hierarchical approaches harnessing both land surface and climate predictability. In basins where atmospheric teleconnection signals are strong, and when watershed predictability is low, climate information alone provides considerable improvements. For those basins showing weak teleconnections, custom predictors from reanalysis fields were more effective in forecast skill than standard climate indices. ESP predictions tended to have high correlation skill but greater bias compared to other methods, and climate predictors failed to substantially improve these deficiencies within a trace weighting framework. Lower complexity techniques were competitive with more complex methods, and the hierarchical expert regression approach introduced here (hierarchical ensemble streamflow prediction – HESP) provided a robust alternative for skillful and reliable water supply forecasts at all initialization times. Three key findings from this effort are (1) objective approaches supporting methodologically consistent hindcasts open the door to a broad range of beneficial forecasting strategies; (2) the use of climate predictors can add to the seasonal forecast skill available from IHCs; and (3) sample size limitations must be handled rigorously to avoid over-trained forecast solutions. Overall, the results suggest that despite a rich, long heritage of operational use, there remain a number of compelling opportunities to improve the skill and value of seasonal streamflow predictions.
A steadily increasing number of research trials and prevention advocates are identifying the practice environment as the main source of both problems and solutions to the improved delivery of ...clinical preventive services. Although these sources are correctly focusing on office systems as solutions, there is a tendency to focus on only parts of a system and to relate this to just one or a few related preventive services. However, the effort required to set up and maintain an office system makes it difficult to justify doing so for a single clinical activity. The process and system thinking of Continuous Quality Improvement (CQI) theory suggests that there may be both efficiency and effectiveness advantages to the concept of all clinical preventive services being served by a single system with many interrelated component processes. Such a system should be usable for all age groups. This system and its literature base are described. The feasibility of applying this concept is being tested in a randomized controlled trial in 44 primary care clinics in Minnesota and Wisconsin.
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