Showing papers by "Paul P. Lee published in 2011"

Molecular Epidemiology of Human Coronavirus OC43 Reveals Evolution of Different Genotypes over Time and Recent Emergence of a Novel Genotype due to Natural Recombination

Abstract: Although human coronavirus OC43-OC43 (HCoV-OC43) is the coronavirus most commonly associated with human infections, little is known about its molecular epidemiology and evolution. We conducted a molecular epidemiology study to investigate different genotypes and potential recombination in HCoV-OC43. Twenty-nine HCoV-OC43 strains from nasopharyngeal aspirates, collected from 2004 to 2011, were subjected to RNA-dependent RNA polymerase (RdRp), spike, and nucleocapsid gene analysis. Phylogenetic analysis showed at least three distinct clusters of HCoV-OC43, although 10 unusual strains displayed incongruent phylogenetic positions between RdRp and spike genes. This suggested the presence of four HCoV-OC43 genotypes (A to D), with genotype D most likely arising from recombination. The complete genome sequencing of two genotype C and D strains and bootscan analysis showed recombination events between genotypes B and C in the generation of genotype D. Of the 29 strains, none belonged to the more ancient genotype A, 5 from 2004 belonged to genotype B, 15 from 2004 to 2006 belonged to genotype C, and 1 from 2004 and all 8 from 2008 to 2011 belonged to the recombinant genotype D. Molecular clock analysis using spike and nucleocapsid genes dated the most recent common ancestor of all genotypes to the 1950s, genotype B and C to the 1980s, genotype B to the 1990s, and genotype C to the late 1990s to early 2000s, while the recombinant genotype D strains were detected as early as 2004. This represents the first study to describe natural recombination in HCoV-OC43 and the evolution of different genotypes over time, leading to the emergence of novel genotype D, which is associated with pneumonia in our elderly population.

Ocular Complications After Anti-vascular Endothelial Growth Factor Therapy In Medicare Patients With Age-related Macular Degeneration

Abstract: Purpose To determine longitudinal rates of ocular complications after anti–vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD) in a nationally representative longitudinal sample. Design Retrospective, longitudinal case-control study. Methods Using the Medicare 5% claims database, diagnoses of neovascular AMD and anti-VEGF injections of ranibizumab, bevacizumab, or pegaptanib were identified from International Classification of Diseases and Current Procedural Terminology procedure codes. Six thousand one hundred fifty-four individuals undergoing anti-VEGF treatment for neovascular AMD (total of 40 903 injections) were compared with 6154 matched controls with neovascular AMD who did not undergo anti-VEGF treatment. Propensity score matching was used to match individuals receiving anti-VEGF injections with controls. Rates of postinjection adverse outcomes (endophthalmitis, rhegmatogenous retinal detachment, retinal tear, uveitis, and vitreous hemorrhage) were analyzed by cumulative incidence and Cox proportional hazards model to control for demographic factors and ocular comorbidities. Results At the 2-year follow-up, the rates of endophthalmitis per injection (0.09%; P P P P Conclusions Rates of endophthalmitis, uveitis, and vitreous hemorrhage were higher in the group treated with anti-VEGF injection than in the control group, although these nevertheless were rare in both groups. The overall risk of severe ocular complications was significantly higher in the anti-VEGF treatment group.

Estimated cases of legal blindness and visual impairment avoided using ranibizumab for choroidal neovascularization: non-Hispanic white population in the United States with age-related macular degeneration.

Abstract: Objective To estimate the number of non-Hispanic white individuals in the United States avoiding legal blindness and visual impairment from neovascular age-related macular degeneration (AMD) with ranibizumab availability. Methods Modeling of visual acuity outcomes from phase 3 ranibizumab trials to incidence rates of neovascular AMD from population-based studies. Results If no treatment were given, of the 103 582 individuals developing neovascular AMD for which ranibizumab would be indicated and available, 16 268 would become legally blind in 2 years. Monthly ranibizumab would reduce the incidence of legal blindness in 2 years by 72% (95% confidence interval [CI], 70% to 74%) to 4484 individuals. If no treatment were given, 34 702 would become visually impaired. Monthly ranibizumab would reduce the incidence of visual impairment in 2 years by 37% (95% CI, 35% to 39%) to 21 919 cases. Conclusions Ranibizumab should have a substantial effect on reducing the magnitude of legal blindness and visual impairment within 2 years after diagnosis of neovascular AMD among non-Hispanic white individuals in the United States. Although racial subgroups other than non-Hispanic whites were not considered (because there is limited information in the literature regarding incidence rates of choroidal neovascularization in other populations) and although these results assume access to and application of monthly ranibizumab for 2 years, the number of individuals developing legal blindness or vision impairment from neovascular AMD should be reduced dramatically if monthly ranibizumab is applied when indicated.

Complete genome analysis of three novel picornaviruses from diverse bat species

Abstract: Although bats are important reservoirs of diverse viruses that can cause human epidemics, little is known about the presence of picornaviruses in these flying mammals. Among 1,108 bats of 18 species studied, three novel picornaviruses (groups 1, 2, and 3) were identified from alimentary specimens of 12 bats from five species and four genera. Two complete genomes, each from the three picornaviruses, were sequenced. Phylogenetic analysis showed that they fell into three distinct clusters in the Picornaviridae family, with low homologies to known picornaviruses, especially in leader and 2A proteins. Moreover, group 1 and 2 viruses are more closely related to each other than to group 3 viruses, which exhibit genome features distinct from those of the former two virus groups. In particular, the group 3 virus genome contains the shortest leader protein within Picornaviridae, a putative type I internal ribosome entry site (IRES) in the 5'-untranslated region instead of the type IV IRES found in group 1 and 2 viruses, one instead of two GXCG motifs in 2A, an L→V substitution in the DDLXQ motif in 2C helicase, and a conserved GXH motif in 3C protease. Group 1 and 2 viruses are unique among picornaviruses in having AMH instead of the GXH motif in 3C(pro). These findings suggest that the three picornaviruses belong to two novel genera in the Picornaviridae family. This report describes the discovery and complete genome analysis of three picornaviruses in bats, and their presence in diverse bat genera/species suggests the ability to cross the species barrier.

Glaucoma medication adherence: room for improvement in both performance and measurement.

Abstract: Glaucoma is the leading cause of irreversible blindness worldwide1,2 and the number of Americans with glaucoma is expected to increase by 50% in the next 15 years.3 Multiple clinical trials have shown that with effective medical treatment, much (but not all) vision loss can be prevented.4–6 Whether measured by pharmacy data,7 self-report,8,9 or medication monitor,10 adherence to glaucoma medication is often poor. Investigators studying medication adherence have identified multiple factors related to poor adherence, including more frequent11 and complex12 dosing and situational factors, such as competing activities12 and forgetfulness,8 as well as patient-centered factors, such as poor disease knowledge,13 poor health literacy,14 and a passive learning style.13 This information is important because the identification of barriers to adherence facilitates a better understanding of the problems and possible interventions to reduce these barriers. However, to critique the success or failure of such interventions, we need to use comprehensive and accurate measurements of adherence. In this editorial, we have attempted to construct a framework for the components of medication adherence and review the metrics available for quantifying adherence.

Can topical ketorolac 0.5% improve the function of Ahmed® glaucoma drainage devices?

Abstract: BACKGROUND AND OBJECTIVE To determine whether postoperative use of topical ketorolac tromethamine 0.5% affects intraocular pressure (IOP) following Ahmed glaucoma drainage device (New World Medical, Inc., Rancho Cucamonga, CA) implantation. PATIENTS AND METHODS Patients undergoing Ahmed implantation at the University of Michigan from January 2002 to June 2008 were reviewed. Fourteen eyes received ketorolac after surgery; 50 eyes did not. Preoperative and postoperative IOP and glaucoma medications were recorded for both groups; the two-sided Student's t test was used to compare these parameters. RESULTS Mean preoperative IOP was similar in the two groups (35.1 ± 11.9 vs 37.0 ± 12.2 mm Hg; P = .60). At postoperative month 6, the ketorolac group had significantly lower IOP compared with the no ketorolac group (13.1 ± 3.7 vs 19.5 ± 9.3 mm Hg, respectively; P = .0003). There was no difference in the number of glaucoma medications postoperatively between the two groups. CONCLUSION Ketorolac may lead to lower postoperative IOP following Ahmed implantation.

Most Claims Settle: Implications for Alternative Dispute Resolution from A Profile of Medical-Malpractice Claims in Florida

Abstract: I INTRODUCTION Past research on the nature and scope of medical-malpractice claims in Florida has found that a very high number of cases are resolved before trial, and, conversely, a very low number of cases are resolved through jury trials A general survey of the process of medical-malpractice claims resolution in Florida between 1990 and 2003 reveals that 45% of claims resulted in payments, 46% of paid claims were closed in three years, and 96% were closed in six years (1) Moreover, 20% of paid claims were settled without a lawsuit ever being filed, and only 23% of paid claims were resolved following a jury trial Out of all awards equal to or exceeding one million dollars, approximately 10% were made without a plaintiff ever filing a formal lawsuit, compared to less than 5% of cases resolved through jury trial (2) Numerous researchers have studied when parties in a legal dispute go to trial and when they settle out of court(3) These investigations--which often use the Pareto notion of equality (4) tested with game-theoretic models--have focused on the strategic decision-making elements of pretrial settlements These studies have found that each party's level of information, as well as the rules of the game, affect the likelihood of settlement(5) The few studies that have used real data to examine settlement rates have found very high pretrial-settlement rates (6) The dynamics behind these resolution rates--whether they are million-dollar cases, lesser awards, or claims without awards--should be considered in the context of the discovery and procedural rules guiding the claiming process A study of closed-claim files of major medical-liability insurers clearly demonstrates the importance of the discovery process in resolving claims (7) Before claims can be settled, both parties need to uncover the facts bearing on the dispute, including both the determination of causality and the presence of legal negligence Today, a patient in a hospital is often treated by multiple specialists, resident physicians, nurses, and technicians At the beginning of a claim, no one may know if, which, and how many of these persons might have been negligent (8) The formal process of discovery can be difficult and time-consuming, and undoubtedly is a primary cause of delay in the settlement of most disputes A study of North Carolina closed-claim files found that the information-gathering process often resulted in changes in the insurers' evaluations of the cases (9) For instance, an initial defense expert might say there was no negligence; but after consulting with other experts, the defense lawyer and liability insurer might decide negligence had occurred Indeed, the variation among experts about the presence of negligence is one of the causes of litigation itself (10) Deposing the plaintiff's experts might change the insurer's evaluation of the claim's merit still again Despite claims about "nuisance settlements," insurers are reluctant to settle cases unless there is substantial evidence of legal negligence on the part of the insured (11) Similarly, the results of the discovery process often cause plaintiffs to abandon claims when they conclude that negligence cannot be proven or, in any event, that the costs of litigation would offset any potential recovery In short, this article contributes to the topic of alternative dispute resolution (ADR) by drawing attention to the frequent and complicated evidentiary problems in medical malpractice claims and the procedural mechanisms provided by statutes, court rules, and case law that are already in place to facilitate claim resolution Other states have procedural mechanisms similar to those in Florida As such, while proposed ADR procedures might well provide better resolutions to medical malpractice claims, they must take into consideration both the unique characteristics of medical malpractice disputes and existing mechanisms for resolving these disputes …