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Highly Effective (highly + effective)
Terms modified by Highly Effective Selected AbstractsChemInform Abstract: p-Toluenesulfonic Acid Mediated Zinc Chloride: Highly Effective for the Beckmann Rearrangement.CHEMINFORM, Issue 2 2008Lin-fei Xiao Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] A Highly Effective (Triphenyl phosphite)palladium Catalyst for a Cross,Coupling Reaction of Allylic Alcohols with Organoboronic Acids.CHEMINFORM, Issue 13 2005Yoshihito Kayaki Abstract For Abstract see ChemInform Abstract in Full Text. [source] A Highly Effective Bis(sulfonamide),Diamine Ligand: A Unique Chiral Skeleton for the Enantioselective Cu-Catalyzed Henry ReactionCHEMISTRY - A EUROPEAN JOURNAL, Issue 28 2010Wei Jin A skeleton in the closet! As a unique chiral skeleton, the newly developed bis(sulfonamide),diamine, which contains both diamine and bis(sulfonamide) moieties, was a highly effective ligand for the asymmetric Cu(OAc)2 -catalyzed Henry reaction between nitromethane and aldehydes with a low catalyst loading at room temperature (see scheme). Both aliphatic and aromatic aldehydes gave excellent enantioselectivities of up to 99,%,ee. [source] Asymmetric Desymmetrization Based on an Intramolecular Haloetherification: A Highly Effective and Recyclable Chiral Nonracemic Auxiliary, 2- exo -Methyl-3- endo -phenyl-5-norbornene-2-carboxaldehyde, for meso -1,3- and meso -1,4-DiolsCHEMISTRY - A EUROPEAN JOURNAL, Issue 21 2004Hiromichi Fujioka Prof. Dr. Abstract A new chiral auxiliary, a 3- endo -phenyl norbornene aldehyde derivative, which is a crystalline, very stable, and easily handled, was developed for the desymmetrization of meso -1,3- and meso -1,4-diols. The key step of the method, an intramolecular bromoetherification, proceeded in a highly diastereoselective manner. A four-step sequence, 1) acetalization, 2) intramolecular bromoetherification followed by acid hydrolysis, 3) protection of the alcohol, and 4) retrobromoetherification, transformed the meso -diols into optically active derivatives. The 3- endo -phenyl norbornene aldehyde derivative was simultaneously reformed and could be used repeatedly. This is the first chemical example of a single auxiliary that is applicable for highly enantioselective desymmetrization of meso -1,3- and meso -1,4-diols; to the best of our knowledge, this is the best chemical method available for the desymmetrization of meso -1,4-diols. [source] Treatment of erythrodermic psoriasis in HCV+ patient with adalimumabDERMATOLOGIC THERAPY, Issue 2009Antonio Giovanni Richetta ABSTRACT Erythrodermic psoriasis is a severe and disabling variant of psoriasis. The authors present the case of a 48-year-old man with psoriasis and hemophilia presented with a history of hepatitis C virus (HCV) infection treated with pegylated interferon alpha-2a and ribavirin therapy. At the end of antiviral therapy, skin manifestation progressively worsened, becoming erythrodermic, with lack of efficacy of steroid therapy. The authors decided to start biological therapy with induction dose of adalimumab (Humira, Abbott Laboratories, Abbott Park, Chicago, IL) 80 mg at Week 0 and 40 mg weekly. In our case, this resulted in a highly effective and safe treatment. [source] Efficient and selective tumor cell lysis and induction of apoptosis in melanoma cells by a conditional replication-competent CD95L adenovirusEXPERIMENTAL DERMATOLOGY, Issue 8 2010Lothar F. Fecker Please cite this paper as: Efficient and selective tumor cell lysis and induction of apoptosis in melanoma cells by a conditional replication-competent CD95L adenovirus. Experimental Dermatology 2010; 19: e56,e66. Abstract:, The high mortality of melanoma demands the development of new strategies, and gene therapy may be considered provided improvements in efficacy and selectivity. Overexpression of the death ligand CD95L/FasL has been shown in previous studies as highly effective for apoptosis induction in melanoma cells. For efficient and selective targeting of melanoma, a conditional replication-competent adenoviral vector was constructed (Ad5-FFE-02), which drives CD95L expression by a tetracycline-inducible promoter. For restricting its replication to melanoma cells, the adenoviral E1A gene is controlled by a tyrosinase-derived promoter. Furthermore, adenoviral E1B was deleted and a mutated E1A was used to preferentially support replication in tumor cells. Proving its high selectivity and efficiency, strong expression of E1A and doxycycline-dependent induction of CD95L were characteristic for tyrosinase-positive melanoma cells after Ad5-FFE-02 transduction, whereas absent in non-melanoma cell lines. Importantly, Ad5-FFE-02-mediated cell lysis was restricted to melanoma cells, and induction of apoptosis was found only in tyrosinase and CD95 expressing cells. Finally, the combination of adenoviral replication and CD95L-mediated apoptosis resulted in an enhanced repression of melanoma cell growth. This new adenoviral vector may provide a basis for an efficient targeting of melanoma. [source] Principles and approaches to abate seabird by-catch in longline fisheriesFISH AND FISHERIES, Issue 1 2005Eric Gilman Abstract Mortality in longline fisheries is a critical global threat to most albatross and large petrel species. Here we identify key principles and approaches to identify and achieve broad use of effective seabird by-catch avoidance methods. Despite the availability of highly effective and cost-saving seabird avoidance methods, few longline fleets employ them. Given the political context and capacity of management authorities of the majority of longline fisheries, it is critical to identify seabird avoidance strategies that are not only highly effective, but are also economically viable and commercially practical. Adoption of an international performance standard for longline baited hook,sink rate, and prescribing minimum gear weighting designs that meet this standard that are achievable by all longline fisheries, would be an important step forward towards resolving low use of seabird avoidance methods by vessels, including those in illegal, unregulated and unreported fisheries. Due to differences between fleets, no single seabird avoidance measure is likely to be effective and practical in all longline fisheries. Therefore, testing of seabird avoidance methods in individual fleets is needed to determine efficacy and economic viability. Longline fishers should directly participate in these trials as they have a large repository of knowledge and skills to effectively develop and improve seabird by-catch avoidance techniques, and this provides industry with a sense of ownership for uptake of effective by-catch reduction methods. Establishing protected areas containing seabird colonies and adjacent waters within a nation's EEZ can be an expedient method to address seabird by-catch. However, establishing high seas marine protected areas to restrict longline fishing in seabird foraging areas, which would require extensive and dynamic boundaries and large buffer zones, may not be a viable short-term solution because of the extensive time anticipated to resolve legal complications with international treaties, to achieve international consensus and political will, and to acquire requisite extensive resources for surveillance and enforcement. Analysis of results of research on seabird avoidance methods reveals that the most reliable comparisons of the efficacy of alternative strategies are from comparing the effectiveness of methods tested in a single experiment. Benefits from standardizing the reporting of seabird by-catch rates to account for seabird abundance are described. To provide the most precise inputs for seabird population models, estimates of seabird mortality in longline fisheries should account for seabird falloff from hooks before hauling, delayed mortality of seabirds caught but freed from gear, and mortality caused by hooks discarded in offal. [source] Numerical simulation of mold filling in injection molding using a three-dimensional finite volume approachINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 2 2001Rong-yeu Chang Abstract This work presents an implicit finite volume approach to simulate the three-dimensional mold filling problems encountered during the injection molding. The described numerical model deals with the three-dimensional isothermal flow of incompressible, high-viscous Newtonian fluids with moving interfaces. The collocated finite volume method and the SIMPLE segregated algorithm are used to discretize and solve the Navier,Stokes equation. In addition, a bounded compressive high-resolution differencing scheme is adopted to solve the advection equation to capture the interface on a Eulerian framework. This approach effectively solves the flow field in terms of CPU time and memory storage as well as the complicated three-dimensional melt front topology. Several two- and three-dimensional examples are presented to validate the presented approach and illustrate its capabilities. This method can more accurately predict the critical three-dimensional phenomena encountered during mold filling than the existing Hele,Shaw analysis model. The presented numerical approach has been proven to be a highly effective and flexible tool for simulating mold filling problems. Copyright © 2001 John Wiley & Sons, Ltd. [source] Treatment of linear and spider telangiectasia with an intense pulsed light sourceJOURNAL OF COSMETIC DERMATOLOGY, Issue 4 2004R A Retamar Summary Background, The flashlamp-pumped pulsed dye laser (585 and 577 nm) has proved to be an effective and safe treatment option in the therapy of linear and spider facial telangiectasia. Nevertheless, the postoperative purpura, which most patients see as cosmetically disfiguring, has always been a matter of concern. Aims, To test the effectiveness and safety of an intense pulsed light source (IPLS), which emits non-coherent light adjustable within the 515,1200 nm range, in the treatment of linear and spider facial telangiectasia. Patients & Methods, One hundred and forty patients with linear and stellate facial telangiectasia were treated with an IPLS. Results, In 94 (67.1%) the results were considered excellent (clearance of 80,100%), 43 (30.7%) showed good results (clearance of 40,80%) and in 3 patients (2.1%) the results were poor (clearance < 40%). Post-treatment side effects were minimal and well tolerated. There were no instances of scarring or other permanent side effects. Owing to the large spot size, a large area could be treated within one session. No anaesthesia was required. Conclusion, IPLS is a highly effective and comparably safe therapeutic alternative to the pulsed dye laser in the treatment of facial telangiectasia. The rate of cosmetically relevant side effects is considerably smaller, patient compliance is excellent and the method can easily be applied in an outpatient setting. [source] A comparative study of transformational leadership in nursing development units and conventional clinical settingsJOURNAL OF NURSING MANAGEMENT, Issue 2 2000A. Bowles RMN Aims This is a comparative study of the leadership provided by nurse managers and leaders in Nursing Development Units and conventional clinical settings in England. Background Nursing development units (NDUs) were originally conceived as centres of nursing excellence, innovation and leadership development. This article describes the first published use of a leadership practices inventory (LPI) explicitly based upon a model of transformational leadership. This style of leadership has been commended as highly effective and suitable for nursing. Methods The use of the LPI was piloted as a postal questionnaire and as a schedule for telephone interviewing, these pilots supported the use of telephone interviewing in the main study. Two matched samples of 70 nurses in total were recruited from across England, comprising 14 nurse leaders and 56 of their day to day colleagues. Data was collected by telephone interviewing over a 6-week period between February and April 1998. Six null hypotheses were developed to identify significant inter-group differences in leadership behaviour. Descriptive and inferential data analysis techniques were employed using SPSS for Windows. Findings The leadership provided by NDU leaders was evaluated more highly than non-NDU leaders. A higher level of congruence between self and observer evaluations was shown by NDU leaders. Statistically significant inter-group differences were apparent in three of the five practices of exemplary leadership and in the overall leadership behaviour. NDU leaders show greater self awareness and are more transformational than their non-NDU counterparts. The limitations of the study design are discussed. Conclusions NDU leaders provide leadership of a more transformational nature than their counterparts working in conventional settings. This finding suggests that NDU leaders have enhanced leadership potential and that formalizing nursing development within NDUs may promote the emergence of transformational leadership and provide a microculture in which it might flourish. The LPI is regarded as a useful, adaptable tool suitable for use in UK nursing applications including research, leadership development and education. [source] Combining etanercept with traditional agents in the treatment of psoriasis: a review of the clinical evidenceJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2010PA Foley Abstract Psoriasis is a chronic, systemic inflammatory disorder manifesting primarily in skin and potentially in joints, frequently necessitating treatment with conventional systemic therapies, phototherapy or biological agents. Patients with moderate to severe disease suffer a diminished quality of life, experience significant comorbidities and have a higher mortality. Although traditional treatments are effective in the short-term, their use is often limited by concerns over long-term toxicity, including end-organ damage and risk of malignancy. Combination therapy is a commonly used approach and is often more effective than any single agent. Lower doses of two treatments in combination can also minimize potential side effects from a single agent at higher doses. Etanercept is a recombinant human tumour necrosis factor (TNF), receptor (p75) protein fused with the Fc portion of IgG1 that binds to TNF,. This article reviews the evidence on the efficacy and safety of etanercept in combination with methotrexate, acitretin, narrowband UVB and cyclosporin. The largest body of evidence assesses the combination with methotrexate, although evidence is available for the other combinations. Data suggest that although highly effective as monotherapy, etanercept in combination with a conventional systemic agent can enhance efficacy and allow drug sparing. Potentially, the combination may also result in faster treatment responses and permit safe transitioning from one systemic agent to another. Evidence to date suggests that these benefits can be achieved without significant additional toxicity, although long-term data on the efficacy and safety of the combination in psoriatic populations is limited and further evaluation is warranted. [source] Clinical trial: cyclophosphamide pulse therapy , a promising therapeutic alternative in refractory Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2009K. J. SCHMIDT Summary Background, In severe steroid-refractory Crohn's disease (CD), established therapies fail in a relevant proportion of patients. Recent pilot studies indicated the efficacy of cyclophosphamide pulse therapy in these patients. Aim, To provide further and substantial evidence for the rationale to apply cyclophosphamide pulse therapy as therapeutic option in severe courses of CD. Methods, Fifteen patients with steroid-refractory (n = 13) or steroid-dependent (n = 2) CD received 2,6 (median 3) monthly pulses of 750 mg cyclophosphamide in an open-label fashion. Eleven patients were on concomitant immunosuppression (azathioprine/mercaptopurine n = 9; methotrexate n = 2). Results, Thirteen of 15 patients (87%) had a clinical response (CDAI decrease >100). Ten patients (67%) went into remission (CDAI <150) after 8 weeks. Steroid-free remission was achieved in eight patients (54%). Two patients (13%) failed to respond. Median CDAI decreased from 420 (245,550) to 100 (26,538) at week 8. Remission lasted 16 months (median, range 4,40). In three patients, arthritis, erythema nodosum and episcleritis completely resolved. Cyclophosphamide pulse therapy administration was well tolerated in all subjects. Conclusions, Cyclophosphamide pulse therapy is safe and highly effective for induction and maintenance of remission in steroid-refractory/-dependent CD. There is a strong need for additional experience to improve the setting of the encouraging cyclophosphamide treatment in CD. [source] Review article: appropriate use of corticosteroids in Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2007P. M. IRVING Summary Background, Corticosteroids are a well-established treatment for active Crohn's disease and have been widely used for decades. It has become apparent, however, that a proportion of patients either fails to respond to corticosteroids or is unable to withdraw from them without relapsing. Furthermore, their use is associated with a range of side effects, such that long-term treatment carries unacceptable risk. Aim, To review the evidence regarding the appropriate use of corticosteroids in Crohn's disease, along with their side effects, safety and alternatives. Methods, To collect relevant articles, a PubMed search was performed from 1966 to November 2006 using the terms ,steroid', ,corticosteroid', ,glucocorticoid', ,prednisolone', ,prednisone', ,methylprednislone', ,hydrocortisone', ,dexamethasone' and ,budesonide' in combination with ,Crohn(s) disease'. Relevant articles were reviewed, as were their reference lists to identify further articles. Results, When used correctly, corticosteroids are a highly effective, well tolerated, cheap and generally safe treatment for active Crohn' disease. Nevertheless, approximately 50% of recipients will either fail to respond (steroid-resistant) or will be steroid dependent at 1 year. Newer alternatives to corticosteroids are not, however, without risk themselves and, moreover, are not necessarily available universally. Conclusions, Steroids are used widely to treat Crohn's disease, a situation that is unlikely to change in the near future. Accordingly, efforts should be made to ensure that they are used correctly and that their side effects are minimized. Reference is made to recently published guidelines and a simplified ,users guide' is presented. [source] Cure of Helicobacter pylori infection in elderly patients: comparison of low versus high doses of clarithromycin in combination with amoxicillin and pantoprazoleALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2001A. Pilotto Background: Advancing age may influence clarithromycin's pharmacokinetics. No studies have yet compared the effects of different dosages of clarithromycin in combination with a proton pump inhibitor and amoxicillin in elderly patients. Aim: To compare the efficacy and tolerability of clarithromycin 250 mg vs. clarithromycin 500 mg twice daily (b.d.) in combination with pantoprazole and amoxicillin in elderly patients. Methods: One hundred and fifty-four elderly patients with H. pylori -associated ulcer disease or chronic gastritis were consecutively randomized to receive pantoprazole 40 mg daily plus amoxicillin 1 g, and either clarithromycin 250 mg b.d. (PAC 250) or clarithromycin 500 mg b.d. (PAC 500). Two months after therapy, endoscopy and gastric biopsies were repeated. Results: The cure rates of H. pylori infection in the PAC 250 and PAC 500 groups were, respectively, 83% and 79% (ITT analysis) and 94% and 88% (PP analysis) (P=N.S.). Significant decreases in chronic gastritis activity both in the body (P < 0.00001) and the antrum (P < 0.0001) of the stomach were found in H. pylori -cured patients, independently of clarithromycin dosage. Four patients in PAC 250 (5%) and seven in PAC 500 (9%) reported adverse events (P=N.S.). One patient in PAC 250 (25%) and three in PAC 500 (43%) discontinued the study because of these drug-related side-effects (P=N.S.). Conclusions: In elderly patients, 1-week triple therapy with a proton pump inhibitor, amoxicillin and clarithromycin is a highly effective and well tolerated anti- H. pylori treatment. With this combination, clarithromycin at the lower dose of 250 mg b.d. achieved excel- lent cure rates and minimized adverse events and costs. [source] Local oropharyngeal side effects of inhaled corticosteroids in patients with asthmaALLERGY, Issue 5 2006R. Buhl The widespread use of inhaled corticosteroids (ICS) for the treatment of persistent asthma, although highly effective, may be associated with both systemic and local side effects. Systemic side effects of ICS have been extensively studied. In contrast, relatively few studies have been performed to specifically evaluate local side effects of ICS. These local side effects , including oropharyngeal candidiasis, dysphonia, pharyngitis, and cough , are generally viewed as minor complications of therapy. However, they can be clinically significant, affect patient quality of life, hinder compliance with therapy, and mask symptoms of more serious disease. Local side effects result from deposition of an active ICS in the oropharynx during administration of the drug. Numerous factors can influence the proportion of an inhaled dose that is deposited in the oropharyngeal cavity, including the ICS formulation, type of delivery system, and patient compliance with administration instructions. Therefore, the incidence of local side effects can vary widely. The goal in developing a new ICS is to include key pharmacologic characteristics that reduce oropharyngeal exposure to active drug while maintaining efficacy comparable with currently available ICS. [source] Net transition probabilities: an approach to subnational level projections of households and housing demand based on census dataPOPULATION, SPACE AND PLACE (PREVIOUSLY:-INT JOURNAL OF POPULATION GEOGRAPHY), Issue 6 2006Peter McDonald Abstract The authors set out to make medium-term projections of housing demand for subnational regions of Australia. Projections of the numbers of households by household type and age of a household reference person were required. The only possible source of input data at a subnational level was the quinquennial censuses. An innovative approach was developed specifically for the purpose of these projections. This involved the use of ,net transition probabilities' estimated from net changes in household classification types for individuals between censuses in the past, which are then projected into the future. The results of the projection for the period 1996,2001 were evaluated against 2001 Census results. Net transition probabilities were found to be robust, in that their age and sex specific profiles were very similar from one intercensal period to the next. The evaluation concluded that the model used is both practical and highly effective. Overall, the authors found that the projections have a high degree of reliability and produce very useful information concerning the future demand for housing at a regional level. Copyright © 2006 John Wiley & Sons, Ltd. [source] A novel audit model for assessing quality in non-regulated researchQUALITY ASSURANCE JOURNAL, Issue 2 2009S. G. Volsen Abstract The need for Quality standards in non-regulated research is a matter of considerable current debate. Whilst a number of such guidelines have been developed over recent years, their successful implementation remains a challenge to all. In order to assess whether research standards are indeed improving on the bench following the instigation of such a quality system, a question posed by both senior management and scientists alike, an independent compliance programme is required. However, given the lack of predicate rules, naivety to audit process and general sensitivity to external scrutiny within the scientific ranks, then work in this ,Grey Area' generates high exposure for the conventional GLP, GCP or GMP auditor. We have developed, tried, and tested a highly effective, novel audit model for assessing the quality of non-regulated research. This simple system can be applied successfully irrespective of scientific discipline or field. Whilst common principles will always apply during any quality system audit, the refinements and idiosyncrasies we describe here will, as we have found, help underpin success. Our intentional assumption is that this is a first time endeavour for the quality professional. Copyright © 2009 John Wiley & Sons, Ltd. [source] Rapid screening and confirmation of drugs and toxic compounds in biological specimens using liquid chromatography/ion trap tandem mass spectrometry and automated library searchRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 1 2010Hsiu-Chuan Liu Recent advances in liquid chromatography/tandem mass spectrometry (LC/MS/MS) technology have provided an opportunity for the development of more specific approaches to achieve the ,screen' and ,confirmation' goals in a single analytical step. For this purpose, this study adapts the electrospray ionization ion trap LC/MS/MS instrumentation (LC/ESI-MS/MS) for the screening and confirmation of over 800 drugs and toxic compounds in biological specimens. Liquid-liquid and solid-phase extraction protocols were coupled to LC/ESI-MS/MS using a 1.8-µm particle size analytical column operated at 50°C. Gradient elution of the analytes was conducted using a solvent system composed of methanol and water containing 0.1% formic acid. Positive-ion ESI-MS/MS spectra and retention times for each of the 800 drugs and toxic compounds were first established using 1,10,µg/mL standard solutions. This spectra and retention time information was then transferred to the library and searched by the identification algorithm for the confirmation of compounds found in test specimens , based on retention time matches and scores of fit, reverse fit, and purity resulting from the searching process. The established method was found highly effective when applied to the analyses of postmortem specimens (blood, urine, and hair) and external proficiency test samples provided by the College of American Pathology (CAP). The development of this approach has significantly improved the efficiency of our routine laboratory operation that was based on a two-step (immunoassay and GC/MS) approach in the past. Copyright © 2009 John Wiley & Sons, Ltd. [source] Acute stroke therapy with tissue plasminogen activator (tPA) since it was approved by the U.S. Food and Drug Administration (FDA),ANNALS OF NEUROLOGY, Issue 1 2009Justin A. Zivin MD Tissue plasminogen activator (tPA) for acute ischemic stroke was approved by the U.S. Food and Drug Administration (FDA) in 1996. Since then it has been severely underutilized. At the time when most practitioners were first being exposed to the literature concerning tPA, there were many concerns about safety and the restrictions on use were quite onerous. Since then a good deal of further work has been done to loosen the restrictions and allay concerns about the risks. The true risk to benefit ratio is far better than is generally realized. Now it is mostly economic problems related to the costs of constantly supplying emergency care that is limiting access. Furthermore, in the current litigious environment, failure to treat is likely to be a more hazardous course of action than legal exposure due to poor outcomes. It must be emphasized that the drug is quite safe and highly effective, and current utilization rates are unacceptably low. Ann Neurol 2009;66:6,10 [source] The cell death machinery governed by the p53 tumor suppressor in response to DNA damageCANCER SCIENCE, Issue 4 2010Kiyotsugu Yoshida The cellular response to genotoxic stress that damages DNA includes cell cycle arrest, activation of DNA repair, and in the event of irreparable damage, induction of apoptosis. However, the signals that determine cell fate, that is, survival or apoptosis, are largely unclear. The tumor suppressor p53 has been implicated in many important cellular processes, including regulation of apoptotic cell death. When cells encounter genotoxic stress, certain sensors for DNA lesions eventually stabilize and activate p53. Subsequently, p53 exerts its tumor suppressor function by transactivating numerous target genes. Active p53 is subjected to a complex and diverse array of covalent post-translational modifications, which selectively influence the expression of p53 target genes. In this regard, the molecular basis for how p53 induces apoptosis has been extensively studied; however, the relative contribution of each downstream effecter is still to be explored. Moreover, little is known about precise mechanisms by which modified p53 is capable of apoptosis induction. A thorough understanding for the whole picture of p53 modification in apoptosis will be extremely valuable in the development of highly effective and specific therapies for caner patients. This review is focused on the current views regarding the regulation of cell fate by p53 in the apoptotic response to DNA damage. (Cancer Sci 2010; 101: 831,835) [source] Results from the International Cataract Surgery Outcomes StudyACTA OPHTHALMOLOGICA, Issue thesis2 2007Jens Christian Norregaard MD Abstract It is widely accepted that cataract extraction with intraocular lens implantation is a highly effective and successful procedure. However, quality assessments and studies of effectiveness should still be undertaken. As with any surgical treatment modality, complications may occur, leading to suboptimal outcomes, additional health costs and deterioration in patients' functional capacity. International variation in clinical practice patterns and outcomes can serve as important pointers in the attempt to identify areas amenable to improvements in quality and cost-effectiveness. Once demonstrated, similar clinical results obtained in different health care systems can improve the level of confidence in a clinical standard against which the quality of care can be evaluated. The International Cataract Surgery Outcomes Study was established in 1992. The objective of this international comparative research project was to compare cataract management, outcomes of surgery and quality of care in four international sites. The study was conducted in the 1990s, since when many developments and refinements have emerged within cataract surgery. The actual figures reported in this thesis may no longer be of specific relevance as a decade has passed since their collection. However, the research questions and methods used in the study are still highly important and justify the publication of this report. The report deals with problems related to quality assessment, benchmarking, and the establishment and design of nationwide clinical databases , issues that are currently the focus of much attention. Moreover, the problems related to cross-national comparisons are increasingly relevant as more international databases are established. The study makes suggestions on how to report and compare objective as well as subjective criteria for surgery. The issue of how to report subjective criteria is a particular subject of current discussion. Four sites with high-quality health care systems were examined in this study: the USA, Denmark, the Province of Manitoba (Canada), and Barcelona (Spain). The design of the international research programme was based on methods developed by the US National Cataract Surgery Outcomes Study conducted by the US Cataract Patients Outcomes Research Team. The International Cataract Surgery Outcomes Study comprised three separate studies: a survey of ophthalmologists; a prospective cohort study, and a retrospective register-based cohort study. The survey study was based on data generated by a self-administered questionnaire completed by ophthalmologists in the four study areas. The questionnaire examined routine clinical practice involving patients considered for cataract surgery, and included questions on anaesthesia, monitoring and surgical techniques. The prospective cohort study was a large-scale, longitudinal observational study of patients undergoing first-eye cataract surgery in each study site. Patients were sampled consecutively from multiple clinics and followed for 4 months postoperatively. The retrospective cohort study was based on the Danish National Patient Register and claims data from the USA. This study could not be carried out in Barcelona or Manitoba as no suitable administrative databases were available. The papers based on register databases deal with retinal detachment and endophthalmitis but are not included in this thesis as the material was previously reported in my PhD thesis. The application of the studies was highly co-ordinated among the four sites and similar methods and instruments were used for data collection. The development of the data collection strategy, questionnaires, clinical data forms and data analyses were co-ordinated through weekly telephone conferences, annual in-person conferences, correspondence by mail or fax, and the exchange of sas programs and data files via the Internet. The survey study was based on responses from 1121 ophthalmologists in the four sites and results were presented in two papers. Within the previous year the participating ophthalmologists had performed a total of 212 428 cataract surgeries. With regard to preoperative ophthalmic testing, the present study reveals that refraction, fundus examination and A-scanning were performed routinely by most surgeons in all four sites. Other tests were reported to be performed routinely by some surgeons. It is unclear why any surgeon would use these other tests routinely in cataract patients with no ocular comorbidity. It appears that if this recommendation from the US Clinical Practice Guidelines Panel was broadly accepted, the use of these procedures and costs of care could be reduced, especially in Barcelona, the USA and Canada. Restricted use of medical screening tests was reported in Denmark. If this restricted screening were to be implemented in the USA, Canada and Barcelona, it would have significant resource implications. The most striking finding concerned the difference in monitoring practice between Denmark and each of the other three sites. In Denmark, monitoring equipment is seldom used and only occasionally is an anaesthesiologist present during cataract surgery. By contrast, in the other study sites, the presence of an anaesthesiologist using monitoring equipment is the norm. Adopting the Danish model in other sites would potentially yield significant cost savings. The results represent part of the background data used to inform the decision to conduct the two large-scale, multicentre Studies of Medical Testing for Cataract Surgery. The current study is an example of how surveys of clinical practice can pinpoint topics that need to be examined in randomized clinical trials. For the second study, 1422 patients were followed from prior to surgery until 4 months postoperatively. Preoperatively, a medical history was obtained and an ophthalmic examination of each patient performed. After consent had been obtained, patients were contacted for an in-depth telephone interview. The interview was repeated 4 months postoperatively. The interview included the VF-14, an index of functional impairment in patients with cataract. Perioperative data were available for 1344 patients (95%). The 4-month postoperative interview and clinical examination were completed by 1284 patients (91%). Main reasons for not re-evaluating patients were: surgery was cancelled (3%); refusal to participate (2%); lost to follow-up (1%), and death or being too sick (1%). The results have been presented in several papers, of which four are included in this thesis. One paper compared the preoperative clinical status of patients across the four sites and showed differences in both visual acuity (VA) and VF-14 measures. The VF-14 is a questionnaire scoring disability related to vision. The findings suggest that indications for surgery in comparable patients were similar in the USA and Denmark and were more liberal than in Manitoba and Barcelona. The results highlight the need to control for patient case mix when making comparisons among providers in a clinical database. This information is important when planning national databases that aim to compare quality of care. A feasible method may be to use one of the recently developed systems for case severity grading before cataract surgery. In another paper, perioperative clinical practice and rates of early complications following cataract surgery were compared across the four health care systems. Once again, the importance of controlling for case mix was demonstrated. Significant differences in clinical practice patterns were revealed, suggesting a general trend towards slower diffusion of new medical technology in Europe compared with North America. There were significant differences across sites in rates of intra- and early postoperative events. The most important differences were seen for rates of capsular rupture, hyphaema, corneal oedema and elevated pressure. Rates of these adverse events might potentially be minimized if factors responsible for the observed differences could be identified. Our results point towards the need for further research in this area. In a third paper, 4-month VA outcomes were compared across the four sites. When mean postoperative VA or crude proportions of patients with a visual outcome of <,0.67 were compared across sites, a much poorer outcome was seen in Barcelona. However, higher age, poorer general health status, lower preoperative VA and presence of ocular comorbidity were found to be significant risk factors associated with increased likelihood of poorer postoperative VA. The proportions of patients with these risk factors varied across sites. After controlling for the different distributions of these factors, no significant difference remained across the four sites regarding risk of a poor visual outcome. Once again the importance of controlling for case mix was demonstrated. In the fourth paper, we examined the postoperative VF-14 score as a measure of visual outcomes for cataract surgery in health care settings in four countries. Controlling for case mix was also necessary for this variable. After controlling for patient case mix, the odds for achieving an optimal visual function outcome were similar across the four sites. Age, gender and coexisting ocular pathology were important predictors of visual functional outcome. Despite what seemed to be an optimal surgical outcome, a third of patients still experienced visual disabilities in everyday life. A measure of the VF-14 might help to elucidate this issue, especially in any study evaluating the benefits of cataract surgery in a public health care context. [source] | |||||||||||||