Publications by authors named "Michael Gaffney"

39 Publications

Identifying the drivers and constraints to adoption of IPM among arable farmers in the UK and Ireland.

Pest Manag Sci 2021 Sep 15;77(9):4148-4158. Epub 2021 May 15.

Crop Science Department, Teagasc Oak Park Crops Research Centre, Carlow, Ireland.

Background: Arable crops in temperate climatic regions such as the UK and Ireland are subject to a multitude of pests (weeds, diseases and vertebrate/invertebrate pests) that can negatively impact productivity if not properly managed. Integrated pest management (IPM) is widely promoted as a sustainable approach to pest management, yet there are few recent studies assessing adoption levels and factors influencing this in arable cropping systems in the UK and Ireland. This study used an extensive farmer survey to address both these issues.

Results: Adoption levels of various IPM practices varied across the sample depending on a range of factors relating to both farm and farmer characteristics. Positive relationships were observed between IPM adoption and farmed area, and familiarity with IPM. Choice of pest control information sources was also found to be influential on farmer familiarity with IPM, with those who were proactive in seeking information from impartial sources being more engaged and reporting higher levels of adoption.

Conclusion: Policies that encourage farmers to greater levels of engagement with their pest management issues and more proactive information seeking, such as through advisory professionals, more experienced peers through crop walks, open days and discussion groups should be strongly encouraged.
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http://dx.doi.org/10.1002/ps.6452DOI Listing
September 2021

Strengthening the interpretability of clinical trial results by assessing the effect of informative censoring on the primary estimand in PRECISION.

Clin Trials 2020 10 9;17(5):535-544. Epub 2020 Jul 9.

Cleveland Clinic, Cleveland, OH, USA.

Background: The ICH E9(R1) addendum states that the strategy to account for intercurrent events should be included when defining an estimand, the treatment effect to be estimated based on the study objective. The estimator used to assess the treatment effect needs to be aligned with the estimand that accounted for intercurrent events. Regardless of the strategy, missing data resulting from patient premature withdrawal could undermine the robustness of the study results. Informative censoring due to dropouts in an events-based study is one such example. Sensitivity analyses using imputation methods are useful to examine the uncertainty due to informative censoring and address the robustness and strength of the study results.

Methods: We assessed the effect of premature patient withdrawal in the PRECISION study, a randomized non-inferiority clinical trial of patients with chronic arthritic pain that compared the cardiovascular safety of three nonsteroidal anti-inflammatory drugs-based treatment policies or paradigms. The protocol-defined use of concomitant or rescue medications was permitted since changes in pain medications due to insufficient analgesia were expected in patients in this long-term study. Anticipating that premature study discontinuations could potentially lead to informative censoring, a supplementary analysis was pre-specified in which censored outcomes due to the premature study discontinuation were imputed based on adverse events that were clinically associated with the primary endpoint (cardiovascular outcome based on the Antiplatelet Trialists Collaboration composite endpoint). Furthermore, tipping point analyses were conducted to test the robustness of the primary analysis results by assuming data censored not at random. The level of increase at which the primary study conclusion would change was estimated.

Results: For the analysis of time to first primary endpoint event through 30 months, 4065 out of the 24,081 enrolled patients were lost to follow-up, withdrew consent, or were no longer willing to participate in the study. These withdrawals occurred gradually and resulted in a cumulative total of 5893 censored patient-years of observation (10.2%). The rate of discontinuation and the baseline characteristics of the discontinued patients were similar across the three treatment groups. The non-inferiority conclusion from the primary analysis was confirmed in the supplementary analysis incorporating relevant adverse events. Furthermore, tipping point analyses demonstrated that in order to lose non-inferiority in the primary analysis, the risk of primary endpoint events during the censored observation time would have to increase by more than 2.7-fold in the celecoxib group while remaining constant in the other nonsteroidal anti-inflammatory drugs groups, demonstrating that the scenarios where the study results are invalid appear not plausible.

Conclusions: Supplementary and sensitivity analyses presented to address informative censoring in PRECISION helped to further interpret and strengthen the study results.
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http://dx.doi.org/10.1177/1740774520934747DOI Listing
October 2020

The Potential for Decision Support Tools to Improve the Management of Root-Feeding Fly Pests of Vegetables in Western Europe.

Insects 2020 Jun 13;11(6). Epub 2020 Jun 13.

Julius Kühn Institute (JKI), Institute for Plant Protection in Horticulture and Forests, Messeweg 11-12, D-38104 Braunschweig, Germany.

Several important vegetable crops grown outdoors in temperate climates in Europe can be damaged by the root-feeding larvae of Diptera ( , Delia floralis, , , , ). Knowledge of pest insect phenology is a key component of any Integrated Pest Management (IPM) strategy, and this review considers the methods used to monitor and forecast the occurrence of root-feeding flies as a basis for decision-making by growers and the ways that such information can be applied. It has highlighted some current management approaches where such information is very useful for decision support, for example, the management of with insecticidal sprays and the management of all of these pests using crop covers. There are other approaches, particularly those that need to be applied at sowing or transplanting, where knowledge of pest phenology and abundance is less necessary. Going forward, it is likely that the number of insecticidal control options available to European vegetable growers will diminish and they will need to move from a strategy which often involves using a single 'silver bullet' to a combination of approaches/tools with partial effects (applied within an IPM framework). For the less-effective, combined methods, accurate information about pest phenology and abundance and reliable decision support are likely to be extremely important.
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http://dx.doi.org/10.3390/insects11060369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349907PMC
June 2020

Management of yellow dwarf disease in Europe in a post-neonicotinoid agriculture.

Pest Manag Sci 2020 Jul 3;76(7):2276-2285. Epub 2020 May 3.

BGPI, INRAE, Cirad, Institut Agro, Univ Montpellier, Montpellier, France.

Barley/cereal yellow dwarf viruses (YDVs) cause yellow dwarf disease (YDD), which is a continuous risk to cereals production worldwide. These viruses cause leaf yellowing and stunting, resulting in yield reductions of up to 80%. YDVs have been a consistent but low-level problem in European cereal cultivation for the last three decades, mostly due to the availability of several effective insecticides (largely pyrethroids and more recently neonicotinoids) against aphid vectors. However, this has changed recently, with many insecticides being lost, culminating in a recent European Union (EU) regulation prohibiting outdoor use of the neonicotinoid-insecticide compounds. This change is coupled with the growing challenge of insecticide-resistant aphids, the lack of genetic resources against YDVs, and a knowledge deficit around the parameters responsible for the emergence and spread of YDD. This means that economic sustainability of cereal cultivation in several European countries including France and United Kingdom is now again threatened by this aphid-vectored viral disease. In this review, we summarize the current knowledge on the YDV pathosystem, describe management options against YDD, analyse the impacts of the neonicotinoid ban in Europe, and consider future strategies to control YDV. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5835DOI Listing
July 2020

Measuring the unmeasurable? A method to quantify adoption of integrated pest management practices in temperate arable farming systems.

Pest Manag Sci 2019 12 21;75(12):3144-3152. Epub 2019 May 21.

Crop Science Department, Teagasc Oak Park Crops Research Centre, Carlow, Ireland.

Background: The impetus to adopt integrated pest management (IPM) practices has re-emerged in the last decade, mainly as a result of legislative and environmental drivers. However, a significant deficit exists in the ability to practically monitor and measure IPM adoption across arable farms; therefore, the aim of the project reported here was to establish a universal metric for quantifying adoption of IPM in temperate arable farming. This was achieved by: (i) identifying a set of key activities that contribute to IPM; (ii) weighting these in terms of their importance to the achievement of IPM using panels of expert stakeholders to create the metric (scoring system from 0 to 100 indicating level of IPM practised); (iii) surveying arable farmers in the UK and Ireland about their pest management practices; and (iv) measuring level of farmer adoption of IPM using the new metric.

Results: This new metric was found to be based on a consistent conception of IPM between countries and professional groups. The survey results showed that, although level of adoption of IPM practices varied over the sample, all farmers had adopted IPM to some extent (minimum 32.6 [corrected] points, mean score of 67.1), [corrected] but only 15 [corrected] of 225 farmers (5.8%) had adopted more than 67.1% [corrected] of what is theoretically possible, as measured by the new metric.

Conclusion: We believe that this new metric would be a viable and cost-effective system to facilitate the benchmarking and monitoring of national IPM programmes in temperate zone countries with large-scale arable farming systems. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5428DOI Listing
December 2019

Predictors of Neuropsychiatric Adverse Events with Smoking Cessation Medications in the Randomized Controlled EAGLES Trial.

J Gen Intern Med 2019 06 7;34(6):862-870. Epub 2019 Mar 7.

Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Background: Pre-treatment factors that increase smokers' risk of experiencing neuropsychiatric adverse events (NPSAEs) when quitting smoking are unknown.

Objective: To identify baseline smoker characteristics beyond the history of mental illness that predict which participants were more likely to experience moderate to severe NPSAEs in EAGLES.

Design: A prospective correlational cohort study in the context of a multinational, multicenter, double-blind, randomized trial.

Participants: Smokers without (N = 3984; NPC)/with (N = 4050; PC) histories of, or current clinically stable, psychiatric disorders including mood (N = 2882; 71%), anxiety (N = 782; 19%), and psychotic (N = 386; 10%) disorders.

Interventions: Bupropion, 150 mg twice daily, or varenicline, 1 mg twice daily, versus active control (nicotine patch, 21 mg/day with taper) and placebo for 12 weeks with 12-week non-treatment follow-up.

Main Measures: Primary safety outcome was the incidence of a composite measure of moderate/severe NPSAEs. Associations among baseline demographic/clinical characteristics and the primary safety endpoint were analyzed post hoc via generalized linear regression.

Key Results: The incidence of moderate to severe NPSAEs was higher among smokers in the PC (238/4050; 5.9%) than in the NPC (84/3984; 2.1%). Three baseline characteristics predicted increased risk for experiencing clinically significant NPSAEs when quitting regardless of carrying a psychiatric diagnosis: current symptoms of anxiety (for every ~ 4-unit increase in HADS anxiety score, the absolute risk of occurrence of the NPSAE endpoint increased by 1% in both PC and NPC); prior history of suicidal ideation and/or behavior (PC, 4.4% increase; P = 0.001; NPC, 4.1% increase; P = 0.02), and being of White race (versus Black: PC, 2.9% ± 0.9 [SE] increase; P = 0.002; and NPC, 3.4% ± 0.8 [SE] increase; P = 0.001). Among smokers with psychiatric disorders, younger age, female sex, history of substance use disorders, and proxy measures of nicotine dependence or psychiatric illness severity also predicted greater risk. There were no significant interactions between these characteristics and treatment. Smokers with unstable psychiatric disorders or with current, active substance abuse were excluded from the study.

Conclusions: Irrespective of cessation pharmacotherapy use, smokers attempting to quit were more likely to experience moderate to severe NPSAEs if they reported current anxiety or prior suicidal ideation at baseline and were White. In smokers with a psychiatric history, female sex, younger age, and greater severity of nicotine dependence were also predictive.

Trial Registration: ClinicalTrials.gov Identifier: NCT01456936.
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http://dx.doi.org/10.1007/s11606-019-04858-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544691PMC
June 2019

National impact of 13-valent pneumococcal conjugate vaccine on ambulatory care visits for otitis media in children under 5 years in the United States.

Int J Pediatr Otorhinolaryngol 2019 Apr 19;119:96-102. Epub 2019 Jan 19.

Vaccine Clinical Research and Development, Pfizer Inc, Collegeville, PA, USA.

Objective: The 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) were approved in the US in 2000 and 2010, respectively, for active immunization against invasive disease caused by all vaccine serotypes and otitis media (OM) caused by 7 serotypes common to both vaccines, starting at ∼6 weeks of age. This study assessed the impact of PCV13 on OM by evaluating changes in US ambulatory care visit rates between the period before PCV7 (1997-1999), during PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013) among US children <5 years old.

Methods: This ecological study used US National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data. Trend analyses using weighted least-squares regression and mean visit rates were calculated for OM and two control endpoints not likely to be related to either vaccine (skin rash and trauma).

Results: Among children <5 and < 2 years old, the observed reduction in OM visit rates was 22% (95%CI: 12%-32%) and 24% (95%CI: 13%-35%) when comparing PCV13 to PCV7 periods, and 41% (95%CI: 30%-52%) and 48% (95%CI: 37%-59%) when comparing PCV13 to pre-PCV7 periods. Visit rates for skin rash and trauma remained stable.

Conclusion: Significant reductions in US ambulatory care visit rates for OM were observed among children aged <5 years after introduction of PCV13 compared to the periods before and during PCV7; reductions were greatest among children <2 years old. The reductions beyond the PCV7 period support the effectiveness of the vaccine's 6 additional serotypes in preventing OM.
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http://dx.doi.org/10.1016/j.ijporl.2019.01.023DOI Listing
April 2019

Communities ready for takeoff.

Politics Life Sci 2017 ;36(1):14-26

§Department of Agricultural and Biological Engineering,Pennsylvania State University.

Although much of the social science literature supports the importance of community assets for success in many policy areas, these assets are often overlooked when selecting communities for new infrastructure facilities. Extensive collaboration is crucial for the success of environmental and economic projects, yet it often is not adequately addressed when making siting decisions for new projects. This article develops a social asset framework that includes social, creative, and human capital to inform site-selection decisions. This framework is applied to the Northwest Advanced Renewables Alliance project to assess community suitability for biofuel-related developments. This framework is the first to take all necessary community assets into account, providing insight into successful site selection beyond current models. The framework not only serves as a model for future biorefinery projects but also guides tasks that depend on informed location selection for success.
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http://dx.doi.org/10.1017/pls.2017.6DOI Listing
September 2018

Communities ready for takeoff.

Politics Life Sci 2017 ;36(1):14-26

§ Department of Agricultural and Biological Engineering, Pennsylvania State University.

Although much of the social science literature supports the importance of community assets for success in many policy areas, these assets are often overlooked when selecting communities for new infrastructure facilities. Extensive collaboration is crucial for the success of environmental and economic projects, yet it often is not adequately addressed when making siting decisions for new projects. This article develops a social asset framework that includes social, creative, and human capital to inform site-selection decisions. This framework is applied to the Northwest Advanced Renewables Alliance project to assess community suitability for biofuel-related developments. This framework is the first to take all necessary community assets into account, providing insight into successful site selection beyond current models. The framework not only serves as a model for future biorefinery projects but also guides tasks that depend on informed location selection for success.
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May 2018

"Forgotten" Chapters in the History of Transcervical Sterilization: Carl Clauberg and Hans-Joachim Lindemann.

J Hist Med Allied Sci 2017 Jul;72(3):272-301

Center for Health, Law, Ethics and Human Right. Project on Ethics and the Holocaust, Elie Wiesel Center for Jewish Studies, Boston University, 715 Albany Street, Talbot 358 West, Boston MA 02218.

Transcervical sterilization is a non-surgical method of permanent female sterilization that is widely used and critically discussed. A review of the historiography of the method reveals that instances of its coercive use are not included in the historical account. This study offers a reexamination of the work of Carl Clauberg and Hans-Joachim Lindemann, to more deeply contextualize within the framework of current usage the coercive use of transcervical sterilization during the Third Reich and in postwar Germany. This inquiry is based on postwar criminal trial records on Clauberg, and on archival documents detailing Lindemann's activities in 1979. A comparative analysis examines arguments by medical historian Karl-Heinz Roth, and identifies shared characteristics and differences between Clauberg and Lindemann, their methods and scientific connections. The results demonstrate that the technique of transcervical sterilization has an abusive potential that may be explained as a function of the person of the physician, of the scientific method itself, and of societal and political influences. The analysis supports the argument that insights from the cases of Clauberg and Lindemann are transferrable geographically and over time, and have the potential to inform current medical practice, such as transcervical sterilization with the Essure device, whose historiographic exploration remains a desideratum.
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http://dx.doi.org/10.1093/jhmas/jrx018DOI Listing
July 2017

Enhancement of phytochemical content and drying efficiency of onions (Allium cepa L.) through blanching.

J Sci Food Agric 2018 Mar 21;98(4):1300-1309. Epub 2017 Sep 21.

Department of Food Chemistry and Technology, Teagasc Food Research Centre, Ashtown, Dublin, Ireland.

Background: This study investigated the effect of blanching (60, 70 and 80 °C for 1, 3, 5 and 10 min) combined with oven drying at 60 °C on the phenolic compounds, antioxidant activity, colour and drying characteristics (drying time, drying rate constant, effective moisture diffusivity and activation energy) of onion slices.

Results: Blanching of onion slices at 60 °C for 3 min and at 70 °C for 1 min prior to drying increased their bioactive compounds and antioxidant activity compared to the control samples and other treatments. Eighteen drying models were evaluated. The Modified Page and two-term exponential models best represented the drying data. The effective diffusivity ranged from 3.32 × 10 m s (control) to 5.27 × 10 m s , 5.01 × 10 m s , and 4.74 × 10 m s for onions blanched at 60 °C, 70 °C and 80 °C, respectively. The higher activation energy was observed for the control (unblanched) sample and slightly lower values were found for 1 min- and 3 min-blanched samples, confirming the higher drying efficiency as a result of the blanching pre-treatment.

Conclusion: The use of blanching as a pre-treatment before drying of onions resulted in enhanced phytochemical content and drying efficiency. © 2017 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.8594DOI Listing
March 2018

Higher Antioxidant Activity, Total Flavonols, and Specific Quercetin Glucosides in Two Different Onion (Allium cepa L.) Varieties Grown under Organic Production: Results from a 6-Year Field Study.

J Agric Food Chem 2017 Jun 14;65(25):5122-5132. Epub 2017 Jun 14.

Teagasc Food Research Centre , Ashtown, Dublin D15 KN3K, Ireland .

We carried out a 6-year study to assess the effect of conventional, organic, and mixed cultivation practices on bioactive compounds (flavonoids, anthocyanins) and antioxidant capacity in onion. Total flavonoids, total anthocyanins, individual flavonols, individual anthocyanins, and antioxidant activity were measured in two varieties ('Hyskin' and 'Red Baron') grown in a long-term split-plot factorial systems comparison trial. This is the first report of repeated measurements of bioactive content over an extensive time period in a single crop type within the same trial. Antioxidant activity (DPPH and FRAP), total flavonol content, and levels of Q 3,4' D and Q 3 G were higher in both varieties under fully organic compared to fully conventional management. Total flavonoids were higher in 'Red Baron' and when onions were grown under organic soil treatment. Differences were primarily due to different soil management practices used in organic agriculture rather than pesticide/ herbicide application.
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http://dx.doi.org/10.1021/acs.jafc.7b01352DOI Listing
June 2017

An evaluation of increasing sample size based on conditional power.

J Biopharm Stat 2017 7;27(5):797-808. Epub 2017 Mar 7.

b Biostatistics, Harvard School of Public Health , Boston , Massachusetts , USA.

We evaluate properties of sample size re-estimation (SSR) designs similar to the promising zone design considered by Mehta and Pocock (2011). We evaluate these designs under the assumption of a true effect size of 1.1 down to 0.4 of the protocol-specified effect size by six measures: 1. The probability of a sample size increase, 2. The mean proportional increase in sample size given an increase; 3 and 4. The mean true conditional power with and without a sample size increase; 5 and 6. The expected increase in sample size and power due to the SSR procedure. These measures show the probability of a sample size increase and the cost/benefit for given true effect sizes, particularly when the SSR may either be pursuing a small effect size of little clinical importance or be unnecessary when the true effect size is close to the protocol-specified effect size. The results show the clear superiority of conducting the SSR late in the study and the inefficiency of a mid-study SSR. The results indicate that waiting until late in the study for the SSR yields a smaller, better targeted set of studies with a greater increase in overall power than a mid-study SSR.
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http://dx.doi.org/10.1080/10543406.2017.1289943DOI Listing
May 2019

Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis.

N Engl J Med 2016 12 13;375(26):2519-29. Epub 2016 Nov 13.

From the Cleveland Clinic, Cleveland (S.E.N., M.E.H., L.M.W., K.E.W., Q.W., V.M., A.M.L.); Western Sydney University, Campbelltown, NSW, Australia (N.D.Y.); Brigham and Women's Hospital, Harvard Medical School, Boston (D.H.S., P.L.); University Hospital Zurich, Zurich, Switzerland (T.F.L., F.R.); Baylor College of Medicine, Veterans Affairs Medical Center, Houston (D.Y.G.); and State University of New York, Downstate Health Sciences Center (J.S.B.) and Pfizer (M.G., B.B., M.F.B., W.B.), New York.

Background: The cardiovascular safety of celecoxib, as compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs), remains uncertain.

Methods: Patients who required NSAIDs for osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk were randomly assigned to receive celecoxib, ibuprofen, or naproxen. The goal of the trial was to assess the noninferiority of celecoxib with regard to the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke. Noninferiority required a hazard ratio of 1.12 or lower, as well as an upper 97.5% confidence limit of 1.33 or lower in the intention-to-treat population and of 1.40 or lower in the on-treatment population. Gastrointestinal and renal outcomes were also adjudicated.

Results: A total of 24,081 patients were randomly assigned to the celecoxib group (mean [±SD] daily dose, 209±37 mg), the naproxen group (852±103 mg), or the ibuprofen group (2045±246 mg) for a mean treatment duration of 20.3±16.0 months and a mean follow-up period of 34.1±13.4 months. During the trial, 68.8% of the patients stopped taking the study drug, and 27.4% of the patients discontinued follow-up. In the intention-to-treat analyses, a primary outcome event occurred in 188 patients in the celecoxib group (2.3%), 201 patients in the naproxen group (2.5%), and 218 patients in the ibuprofen group (2.7%) (hazard ratio for celecoxib vs. naproxen, 0.93; 95% confidence interval [CI], 0.76 to 1.13; hazard ratio for celecoxib vs. ibuprofen, 0.85; 95% CI, 0.70 to 1.04; P<0.001 for noninferiority in both comparisons). In the on-treatment analysis, a primary outcome event occurred in 134 patients in the celecoxib group (1.7%), 144 patients in the naproxen group (1.8%), and 155 patients in the ibuprofen group (1.9%) (hazard ratio for celecoxib vs. naproxen, 0.90; 95% CI, 0.71 to 1.15; hazard ratio for celecoxib vs. ibuprofen, 0.81; 95% CI, 0.65 to 1.02; P<0.001 for noninferiority in both comparisons). The risk of gastrointestinal events was significantly lower with celecoxib than with naproxen (P=0.01) or ibuprofen (P=0.002); the risk of renal events was significantly lower with celecoxib than with ibuprofen (P=0.004) but was not significantly lower with celecoxib than with naproxen (P=0.19).

Conclusions: At moderate doses, celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety. (Funded by Pfizer; ClinicalTrials.gov number, NCT00346216 .).
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http://dx.doi.org/10.1056/NEJMoa1611593DOI Listing
December 2016

Evaluation of polyphenolic content and antioxidant activity in two onion varieties grown under organic and conventional production systems.

J Sci Food Agric 2017 Jul 12;97(9):2982-2990. Epub 2017 Jan 12.

Teagasc Food Research Centre, Ashtown, Dublin, 15, Ireland.

Background: Onions contain a number of bioactive compounds, in particular polyphenols. They are rich sources of such compounds in the human diet and offer significant health benefits to the consumer. Demand for organic crops is steadily increasing partly based on the expected health benefits of organic food consumption. The current study examines the influence of organic and conventional crop management practices on bioactive polyphenolic content of onion.

Results: We examined the effect of conventional, organic, and mixed cultivation practices on the content of total phenolics, total flavonoids and antioxidant activity in two varieties of onion grown over 4 years in a split-plot factorial systems comparison trial. Levels of total phenolics and total flavonoids showed a significant year-on-year variation and were significantly different between organic and conventional production systems. The levels of total phenolics, total flavonoids and antioxidant activity in general were significantly higher (P < 0.05) under fully organic compared to fully conventional management.

Conclusion: Organic cultivation practices resulted in significantly higher levels of potential bioactive compounds in onion. © 2016 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.8138DOI Listing
July 2017

Potential for transfer of Escherichia coli O157:H7, Listeria monocytogenes and Salmonella Senftenberg from contaminated food waste derived compost and anaerobic digestate liquid to lettuce plants.

Food Microbiol 2016 Oct 23;59:7-13. Epub 2016 Apr 23.

Teagasc Food Research Centre, Ashtown, Dublin 15, Ireland. Electronic address:

The diversion of food wastes from landfill to sustainable disposal methods, such as composting and anaerobic digestion, has led to an increase in the soil amendment products that are now commercially available and which are derived from both of these processes. The use of such products as soil amendments during the production of ready-to-eat (RTE) crops is increasing worldwide. The aim of this study was to investigate the potential of three well-recognised bacterial pathogens of importance to public health, namely Escherichia coli O157:H7, Salmonella Senftenberg and Listeria monocytogenes, to become internalised in lettuce plants from peat growing media amended with contaminated food waste derived compost and anaerobic digestion liquid. The results demonstrated both S. Senftenberg and E. coli O157:H7 are capable of internalisation at lower inoculation levels, compared to previous studies. The internalisation was visualised through confocal microscopy. Internalisation of L. monocytogenes did not occur, however significant levels of L. monocytogenes contamination occurred on the non-sterilised plant surface. Assessing the internalisation potential for each of these pathogens, through the compost and anaerobic digestate matrices, allows for better risk assessment of the use of these products in a horticultural setting.
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http://dx.doi.org/10.1016/j.fm.2016.04.006DOI Listing
October 2016

Statistical issues in the design, conduct and analysis of two large safety studies.

Authors:
Michael Gaffney

Clin Trials 2016 10 30;13(5):513-8. Epub 2016 Jun 30.

Pfizer Inc.-Statistical Research, New York, NY, USA

Background/aims: The emergence, post approval, of serious medical events, which may be associated with the use of a particular drug or class of drugs, is an important public health and regulatory issue. The best method to address this issue is through a large, rigorously designed safety study. Therefore, it is important to elucidate the statistical issues involved in these large safety studies.

Methods: Two such studies are PRECISION and EAGLES. PRECISION is the primary focus of this article. PRECISION is a non-inferiority design with a clinically relevant non-inferiority margin. Statistical issues in the design, conduct and analysis of PRECISION are discussed.

Results: Quantitative and clinical aspects of the selection of the composite primary endpoint, the determination and role of the non-inferiority margin in a large safety study and the intent-to-treat and modified intent-to-treat analyses in a non-inferiority safety study are shown. Protocol changes that were necessary during the conduct of PRECISION are discussed from a statistical perspective. Issues regarding the complex analysis and interpretation of the results of PRECISION are outlined. EAGLES is presented as a large, rigorously designed safety study when a non-inferiority margin was not able to be determined by a strong clinical/scientific method. In general, when a non-inferiority margin is not able to be determined, the width of the 95% confidence interval is a way to size the study and to assess the cost-benefit of relative trial size.

Conclusion: A non-inferiority margin, when able to be determined by a strong scientific method, should be included in a large safety study. Although these studies could not be called "pragmatic," they are examples of best real-world designs to address safety and regulatory concerns.
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http://dx.doi.org/10.1177/1740774516657336DOI Listing
October 2016

Service delivery under translation: multi-stakeholder accountability in the non-profit community sector in New Zealand.

Health Soc Care Community 2017 03 28;25(2):402-413. Epub 2015 Dec 28.

Independent Researcher, Dunedin, New Zealand.

This paper addresses the challenge reported in the research literature of providing adequate accounts of service quality and value to multiple stakeholders. Rather than starting with a particular accountability practice, we examine the accounts of complex service delivery and results from the perspective of five key stakeholder groups. The case study at the empirical centre of this research is a small New Zealand non-profit organisation that provides community-based wraparound casework to young people, and their families, with multiple and complex needs. This paper reports on data collected during 2009-2012 through interviews with five key stakeholders of this service: the young people, the caseworkers, the co-providers, the managers and the funders. Drawing on translation theory, the different points of reference and the consequential shifts in focus, content and meaning within the multiple stakeholder accounts are traced. The findings show that while each stakeholder group brings a unique point of reference to the service delivery, there are degrees of overlap in the focus and content of the accounts. This is particularly evident in the 'relationship' dimension. While overlaps may exist, points of invisibility are also revealed. Accountability tensions can be traced directly to these points of invisibility. As a result of this analysis, it is argued that more explicit attention to the impact of multiple stakeholders at the level of epistemology provides a mechanism for addressing some of the tensions routinely raised.
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http://dx.doi.org/10.1111/hsc.12319DOI Listing
March 2017

Adverse Clinical Outcomes and Resource Utilization Associated with Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus Infections after Elective Surgery.

Surg Infect (Larchmt) 2015 Oct 30;16(5):543-52. Epub 2015 Jun 30.

2 Pfizer, Inc. , New York, New York.

Background: Current studies of post-operative Staphylococcus aureus disease focus primarily on surgical site infections and are often limited to infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The objective of this retrospective cohort analysis was to describe the occurrence of and outcomes associated with post-operative MRSA and methicillin-sensitive S. aureus (MSSA) infections in patients undergoing elective surgical procedures.

Methods: Data were extracted from Health Facts for inpatients aged 18 years or older with pre-defined International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes, meeting additional criteria indicating that the procedure was elective. Post-operative S. aureus infection was identified by one or more qualifying culture positive for MRSA or MSSA. Multivariable regression models compared patients with MRSA, MSSA, and no S. aureus infection.

Results: Among 34,866 qualifying patients, the incidence of S. aureus infections was 0.9% during the index admission and 1.7% within 90 d after elective surgery, of which 36.6% and 38.4% were MRSA, respectively. The highest rates were observed among patients undergoing general surgery (2.2% during index admission, 3.2% within 90 d) and plastic surgery (1.8% during index admission, 3.1% within 90 d). Patients with MRSA and MSSA experienced poorer outcomes than uninfected patients, based on index admission length of stay (LOS; mean, 30.2, 22.7, and 5.7 d, respectively), hospital charges ($165,651, $134,313, and $52,077), and hospital mortality (odds ratios, 6.4 for MRSA, 4.8 for MSSA versus uninfected patients). Relative to MSSA infection, MRSA infection was associated with greater total hospital LOS and hospital charges but not with increased re-admission or mortality.

Conclusions: The burden of post-operative S. aureus infection is shared among elective surgical procedures, however, rates and types of infections vary. Whereas MRSA infection results in substantially greater health care cost and LOS, mortality and re-admission rates are similar among patients with MRSA and MSSA. In elective surgery, infection control and surveillance for both MRSA and MSSA are warranted.
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http://dx.doi.org/10.1089/sur.2013.250DOI Listing
October 2015

Levels of potential bioactive compounds including carotenoids, vitamin C and phenolic compounds, and expression of their cognate biosynthetic genes vary significantly in different varieties of potato (Solanum tuberosum L.) grown under uniform cultural conditions.

J Sci Food Agric 2016 Feb 27;96(3):1018-26. Epub 2015 Apr 27.

School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.

Background: In addition to their high carbohydrate content, potatoes are also an important dietary source of vitamin C and bioactive secondary metabolites, including phenolic compounds and carotenoids, which have been suggested to play a role in human health. The expression of genes encoding key enzymes involved in the synthesis of these compounds was assessed by reverse transcription-quantitative polymerase chain reaction and compared to the accumulation of the corresponding product in seven potato varieties showing contrasting levels of metabolite accumulation.

Results: Strong positive correlations were found between phenolic content in the flesh of tubers and transcript levels of phenylalanine ammonia lyase (PAL) and chalcone synthase (CHS) genes. The expression of PAL and CHS was also related to that of AN1, a transcription factor involved in the synthesis of anthocyanins, suggesting that these genes are regulated in a coordinated manner. No clear relationship was found between transcript levels of phytoene synthase (PSY) or L-galactono-1,4-lactone dehydrogenase (GLDH) genes and total carotenoid or vitamin C accumulation, respectively.

Conclusion: Data indicate that levels of total phenolic and flavonoid compounds in potato are controlled primarily by PAL and CHS gene expression. Transcript levels of PSY and GLDH did not control accumulation of carotenoids or vitamin C.
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http://dx.doi.org/10.1002/jsfa.7189DOI Listing
February 2016

Acute nonarteritic anterior ischemic optic neuropathy and exposure to phosphodiesterase type 5 inhibitors.

J Sex Med 2015 Jan 31;12(1):139-51. Epub 2014 Oct 31.

Pfizer Inc., New York, NY, USA.

Introduction: Nonarteritic anterior ischemic optic neuropathy (NAION), a rare visual disorder, has been reported in men using phosphodiesterase type 5 inhibitors (PDE5i) for erectile dysfunction.

Aim: We examined whether intermittent use of PDE5i is associated with acute NAION onset within approximately five half-lives following drug ingestion.

Methods: One hundred two ophthalmology centers in the United States and Europe identified potential cases of NAION. An expert adjudication committee conducted a blind review of the records of those with recent PDE5i use to classify cases as Definite, Possible, or not NAION. Subjects provided information on PDEi use via telephone interview. Each NAION case's PDE5i exposure immediately prior to onset was compared against his recent patterns of use in an observational case-crossover design. A sample size of 40 cases with intermittent PDE5i exposure in the 30 days prior to NAION onset was needed to detect an odds ratio (OR) of 3.0 with 80% power.

Main Outcome Measures: The daily relative risk for acute NAION on days within five half-lives of PDE5i use vs. other days was estimated via an OR obtained from conditional logistic regression.

Results: Among 43 Definite NAION cases with PDE5i exposure in the prior 30 days, the OR was 2.15 (95% confidence interval [CI]: 1.06, 4.34). When 21 Possible NAION cases were included (n = 64), the OR was 2.36 (95% CI: 1.33, 4.19).

Conclusions: We found an approximately twofold increased risk of acute NAION within five half-lives of PDE5i use compared with use in a more prior time period. Bias from inaccurate recall of exposure was unlikely to have substantially affected the results. Based on our results, we estimate that weekly use of PDE5i adds three NAION cases per 100,000 men 50 years and older annually.
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http://dx.doi.org/10.1111/jsm.12726DOI Listing
January 2015

Variation in bioactive content in broccoli (Brassica oleracea var. italica) grown under conventional and organic production systems.

J Sci Food Agric 2015 Apr 30;95(6):1163-71. Epub 2014 Jul 30.

Teagasc, Ashtown Food Research Centre, Ashtown, Dublin 15, Ireland; Monaghan Mushrooms, Tyholland, Co., Monaghan, Ireland.

Background: Broccoli and other cruciferous vegetables contain a number of bioactive compounds, in particular glucosinolates and polyphenols, which are proposed to confer health benefits to the consumer. Demand for organic crops is at least partly based on a perception that organic crops may contain higher levels of bioactive compounds; however, insufficient research has been carried out to either support or refute such claims.

Results: In this study we examined the effect of conventional, organic, and mixed cultivation practices on the content of total phenolics, total flavonoids, and total and individual glucosinolates in two varieties of broccoli grown over 2 years in a split-plot factorial systems comparison trial. Levels of total phenolics and total flavonoids showed a significant year-on-year variation but were not significantly different between organic and conventional production systems. In contrast, levels of the indolyl glucosinolates glucobrassicin and neoglucobrassicin were significantly higher (P < 0.05) under fully organic compared to fully conventional management.

Conclusion: Organic cultivation practices resulted in significantly higher levels of glucobrassicin and neoglucobrassicin in broccoli florets; however, other investigated compounds were unaffected by production practices.
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http://dx.doi.org/10.1002/jsfa.6804DOI Listing
April 2015

Effect of genotype and environment on the glycoalkaloid content of rare, heritage, and commercial potato varieties.

J Food Sci 2014 May 2;79(5):T1039-48. Epub 2014 Apr 2.

Teagasc Ashtown Food Research Centre, Dublin 15, Ireland; School of Food and Nutritional Sciences, Univ. College Cork, Cork, Ireland.

Unlabelled: Potatoes accumulate toxic steroidal compounds that could be harmful for humans if consumed in high quantities and must be controlled. In this study, we were interested in assessing the levels and variation of glycoalkaloid content in 60 varieties of potato planted in 2 trial sites over 2 y. Total glycoalkaloid levels ranged from 4 to 957 mg/kg of dry weight in the flesh and from 150 to 8133 mg/kg in the skin, with the latter accumulating generally more α-chaconine than α-solanine. Contents in the flesh were below the safe limit for all varieties, but were generally above in the skin. Maximum values in each site and year of cultivation were found for varieties "Beauty of Hebron," "May Queen," and "Arran Pilot" in the skin and "Beauty of Hebron," "International Kidney," and "Congo" in the flesh. Year of cultivation had a significant effect on total glycoalkaloid content (P < 0.0001), with interactions between variety and site of cultivation and variety and year of cultivation also significant (P < 0.0001), implying that environmental effects seem to act differentially and could induce high levels in genetically predisposed varieties.

Practical Application: This paper reports the levels of toxic glycoalkaloids in 60 varieties of potato. Dietary intake and safety of consumers is discussed and varieties used by the potato processing industry are assessed in terms of safety and potential use of waste peel as raw material.
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http://dx.doi.org/10.1111/1750-3841.12443DOI Listing
May 2014

Potential of cultivar and crop management to affect phytochemical content in winter-grown sprouting broccoli (Brassica oleracea L. var. italica).

J Sci Food Agric 2014 Jan 8;94(2):322-30. Epub 2013 Jul 8.

TFRCA, Ashtown, Dublin, 15, Ireland; Teagasc Kinsealy Research Centre, Dublin, 17, Ireland.

Background: Variety and crop management strategies affect the content of bioactive compounds (phenolics, flavonoids and glucosinolates) in green broccoli (calabrese) types, which are cultivated during summer and autumn in temperate European climates. Sprouting broccoli types are morphologically distinct and are grown over the winter season and harvested until early spring. Thus they show considerable potential for development as an import substitution crop for growers and consumers during the 'hungry gap' of early spring. The present study investigated the effect of variety and management practices on phytochemical content in a range of sprouting broccoli varieties.

Results: Yields were significantly higher in white sprouting broccoli varieties. Levels of phenolics and flavonoids were in the range 81.64-297.65 and 16.95-104.80 mg 100 g⁻¹ fresh weight, respectively, depending on year and cultivar, and were highest in variety 'TZ 5052' in both years. In-row spacing did not affect flavonoid content. Phenolic and flavonoid content generally increased with increasing floret maturity and levels were high in edible portions of the crop. Crop wastes (leaf and flower) contained 145.9-239.3 and 21.5-116.6 mg 100 g⁻¹ fresh weight total phenolics and flavonoids, respectively, depending on cultivar, tissue and year. Climatic factors had a significant effect on phenolic and flavonoid content. Levels of total and some individual glucosinolates were higher in sprouting broccoli than in the green broccoli variety 'Ironman'.

Conclusion: Levels of total phenolics, flavonoids and glucosinolates are higher in sprouting than green broccoli types. Sprouting broccoli represents an excellent source of dietary bioactive compounds.
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http://dx.doi.org/10.1002/jsfa.6263DOI Listing
January 2014

Effect of organic, conventional and mixed cultivation practices on soil microbial community structure and nematode abundance in a cultivated onion crop.

J Sci Food Agric 2013 Dec 7;93(15):3700-9. Epub 2013 Jun 7.

Teagasc Kinsealy Research Centre, Dublin, 17, Ireland; Horticulture Development Department, TFRCA, Ashtown, Dublin, 15, Ireland.

Background: Responses of the soil microbial and nematode community to organic and conventional agricultural practices were studied using the Teagasc Kinsealy Systems Comparison trial as the experimental system. The trial is a long-term field experiment which divides conventional and organic agriculture into component pest-control and soil treatment practices. We hypothesised that management practices would affect soil ecology and used community level physiological profiles, microbial and nematode counts, and denaturing gradient gel electrophoresis (DGGE) to characterise soil microbial communities in plots used for onion (Allium cepa L.) cultivation.

Results: Microbial activity and culturable bacterial counts were significantly higher under fully organic management. Culturable fungi, actinomycete and nematode counts showed a consistent trend towards higher numbers under fully organic management but these data were not statistically significant. No differences were found in the fungal/bacterial ratio. DGGE banding patterns and sequencing of excised bands showed clear differences between treatments. Putative onion fungal pathogens were predominantly sequenced under conventional soil treatment practices whilst putative soil suppressive bacterial species were predominantly sequenced from the organic pest-control treatment plots.

Conclusion: Organic management increased microbial activity and diversity. Sequence data was indicative of differences in functional groups and warrants further investigation.
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http://dx.doi.org/10.1002/jsfa.6206DOI Listing
December 2013

Cardiovascular safety of varenicline: patient-level meta-analysis of randomized, blinded, placebo-controlled trials.

Am J Ther 2013 May-Jun;20(3):235-46

Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.

Smoking is a major modifiable risk factor for cardiovascular (CV) disease. Varenicline is a pharmacological aid for smoking cessation. To explore the CV safety of varenicline, we investigated the incidence of CV events in varenicline-treated subjects across all phase 2-4 randomized placebo-controlled clinical trials of ≥12-week treatment duration conducted in smokers aged ≥18 years and sponsored by the drug manufacturer. This manuscript reports a subject-level meta-analysis of time to major adverse cardiovascular events (MACE; defined as CV-related death, nonfatal myocardial infarction, nonfatal stroke) and time to MACE+ (defined as MACE plus worsening or any procedure for peripheral vascular disease, hospitalization for angina, or performance of coronary revascularization). All events were adjudicated by an independent adjudication committee, blind to treatment assignment. Events were assessed during treatment and up to 30 days after the last treatment dose. The primary analytical method was a stratified logrank time-to-event analysis; secondary analyses were meta-analyses of incidence rate ratios and rate differences. Overall, 7002 subjects were included (varenicline: 4190; placebo: 2812) from 15 studies. MACE were reported by 13 varenicline subjects (0.31%) and 6 placebo subjects (0.21%) [hazard ratio, 1.95; 95% confidence interval (CI): 0.79-4.82; P = 0.15; risk difference, 0.006 events per subject-year; 95% CI: -0.003, 0.015, P = 0.19]. MACE+ were reported by 26 varenicline subjects (0.62%) and 12 placebo subjects (0.43%) (hazard ratio, 1.74; 95% CI: 0.91-3.34, P = 0.10; risk difference, 0.010; 95% CI: -0.002, 0.022, P = 0.11). This subject-level meta-analysis of MACE or MACE+ up to 30 days posttreatment in placebo-controlled clinical trials of varenicline found a trend toward increased incidence of these events in varenicline-treated patients that did not reach statistical significance. The overall number of events was low and the absolute risk of CV events with varenicline was small.
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http://dx.doi.org/10.1097/MJT.0b013e31828d455bDOI Listing
October 2013

Feasibility study on the use of visible-near-infrared spectroscopy for the screening of individual and total glucosinolate contents in broccoli.

J Agric Food Chem 2012 Aug 20;60(30):7352-8. Epub 2012 Jul 20.

Food Colour and Quality Laboratory, Department of Nutrition and Food Science, Facultad de Farmacia, Universidad de Sevilla , 41012 Sevilla, Spain.

The potential of visible-near-infrared spectroscopy to determine selected individual and total glucosinolates in broccoli has been evaluated. Modified partial least-squares regression was used to develop quantitative models to predict glucosinolate contents. Both the whole spectrum and different spectral regions were separately evaluated to develop the quantitative models; in all cases the best results were obtained using the near-infrared zone between 2000 and 2498 nm. These models have been externally validated for the screening of glucoraphanin, glucobrassicin, 4-methoxyglucobrassicin, neoglucobrassicin, and total glucosinolates contents. In addition, discriminant partial least-squares was used to distinguish between two possible broccoli cultivars and showed a high degree of accuracy. In the case of the qualitative analysis, best results were obtained using the whole spectrum (i.e., 400-2498 nm) with a correct classification rate of 100% in external validation being obtained.
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http://dx.doi.org/10.1021/jf3018113DOI Listing
August 2012

Psychiatric characteristics associated with long-term mortality among 361 patients having an acute coronary syndrome and major depression: seven-year follow-up of SADHART participants.

Arch Gen Psychiatry 2009 Sep;66(9):1022-9

Department of Psychiatry, Columbia University College of Physicians and Surgeons, New Yourk, NY, USA.

Context: Major depressive disorder (MDD) after acute coronary syndrome (ACS) is associated with an increased mortality rate. We observed the participants of the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) to establish features of MDD associated with long-term mortality.

Objectives: To determine whether the following variables were associated with long-term mortality: baseline depression severity, previous MDD episodes, onset of MDD before or after the ACS event, 6 months of sertraline hydrochloride therapy, and mood improvement independent of treatment.

Design: SADHART was a double-blind, placebo-controlled, randomized trial comparing the safety and antidepressant efficacy of sertraline vs placebo in 369 patients with ACS who met criteria for MDD. The trial was completed in June 2000, and follow-up for vital status was completed in September 2007.

Setting: Academic research.

Participants: SADHART participants.

Main Outcome Measures: Vital status was determined in 361 participants (97.8%) during a median follow-up of 6.7 years.

Results: During the study, 75 participants (20.9%) died. Neither previous episodes of MDD, nor onset before or after the index ACS, nor an initial 6 months of sertraline treatment was associated with long-term mortality. Cox proportional hazards regression models showed that baseline MDD severity (hazard ratio, 2.30; 95% confidence interval, 1.28-4.14; P < .006) and failure of MDD to improve substantially during treatment with either sertraline or placebo (hazard ratio, 2.39; 95% confidence interval, 1.39-2.44; P < .001) were strongly and independently associated with long-term mortality. Marked improvement in depression (Clinical Global Impression-Improvement subscale score of 1) was associated with improved adherence to study medication.

Conclusions: Severity of MDD measured within a few weeks of hospitalization for ACS or failure of MDD to improve during the 6 months following ACS predicted more than a doubling of mortality over 6.7 years of follow-up. Because persistent depression increases mortality and decreases medication adherence, physicians need to aggressively treat depression and be diligent in promoting adherence to guideline cardiovascular drug therapy.
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http://dx.doi.org/10.1001/archgenpsychiatry.2009.121DOI Listing
September 2009

Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment.

Circulation 2008 Jun 2;117(23):3002-9. Epub 2008 Jun 2.

Academic Medical Center, Department of Vascular Medicine, University of Amsterdam, Amsterdam, the Netherlands.

Background: Low-density lipoprotein (LDL) cholesterol is the principal target of lipid-lowering therapy, but recent evidence has suggested more appropriate targets. We compared the relationships of on-treatment levels of LDL cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B, as well as ratios of total/HDL cholesterol, LDL/HDL cholesterol, and apolipoprotein B/A-I, with the occurrence of cardiovascular events in patients receiving statin therapy.

Methods And Results: A post hoc analysis was performed that combined data from 2 prospective, randomized clinical trials in which 10,001 ("Treating to New Targets") and 8888 ("Incremental Decrease in End Points through Aggressive Lipid Lowering") patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment. In models with LDL cholesterol, non-HDL cholesterol and apolipoprotein B were positively associated with cardiovascular outcome, whereas a positive relationship with LDL cholesterol was lost. In a model that contained non-HDL cholesterol and apolipoprotein B, neither was significant owing to collinearity. Total/HDL cholesterol ratio and the apolipoprotein B/A-I ratio in particular were each more closely associated with outcome than any of the individual proatherogenic lipoprotein parameters.

Conclusions: In patients receiving statin therapy, on-treatment levels of non-HDL cholesterol and apolipoprotein B were more closely associated with cardiovascular outcome than levels of LDL cholesterol. Inclusion of measurements of the antiatherogenic lipoprotein fraction further strengthened the relationships. These data support the use of non-HDL cholesterol or apolipoprotein B as novel treatment targets for statin therapy. Given the absence of interventions that have been proven to consistently reduce cardiovascular disease risk through raising plasma levels of HDL cholesterol or apolipoprotein A-I, it seems premature to consider the ratio variables as clinically useful.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.107.713438DOI Listing
June 2008
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