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Annual Review of Medicine - Volume 65, 2014
Volume 65, 2014
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Adult Genetic Risk Screening
Vol. 65 (2014), pp. 1–17More LessRecent advances in genetic analysis especially DNA sequencing technology open a new strategy for adult disease prevention by genetic screening. Physicians presently treat disease pathology with less emphasis on disease risk prevention/reduction. Genetic screening has reduced the incidence of untreatable childhood genetic diseases and improved the care of newborns. The opportunity exists to expand screening programs and reduce the incidence of adult onset diseases via genetic risk identification and disease intervention. This article outlines the approach, challenges, and benefits of such screening for adult genetic disease risks.
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Identification of Genes for Childhood Heritable Diseases
Vol. 65 (2014), pp. 19–31More LessGenes causing rare heritable childhood diseases are being discovered at an accelerating pace driven by the decreasing cost and increasing accessibility of next-generation DNA sequencing combined with the maturation of strategies for successful gene identification. The findings are shedding light on the biological mechanisms of childhood disease and broadening the phenotypic spectrum of many clinical syndromes. Still, thousands of childhood disease genes remain to be identified, and given their increasing rarity, this will require large-scale collaboration that includes mechanisms for sharing phenotypic and genotypic data sets. Nonetheless, genomic technologies are poised for widespread translation to clinical practice for the benefit of children and families living with these rare diseases.
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Genomic Sequencing for Cancer Diagnosis and Therapy
Vol. 65 (2014), pp. 33–48More LessFor a decade, the technologies behind DNA sequencing have improved rapidly in cost reduction and speed. Sequencing in large populations of cancer patients is leading to dramatic advances in our understanding of the cancer genome. The wide variety of cancer types sequenced and analyzed using these technologies has revealed many novel fundamental genetic mechanisms driving cancer initiation, progression, and maintenance. We have deepened our understanding of the signaling pathways, demonstrating disruption in epigenetic regulation and destabilization of the splicing machinery. The molecular mechanisms of resistance to targeted therapies are being elucidated for the first time. The translation of genome-scale variation into clinically actionable information is still in its infancy; nevertheless, insights from sequencing studies have led to the discovery of a variety of novel diagnostic biomarkers and therapeutic targets. Here, we review recent advances in cancer genomics and discuss what the new findings have taught us about cancer biology and, more importantly, how these new findings guide more effective diagnostic and treatment strategies.
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Pathogenesis of Abdominal Aortic Aneurysms: MicroRNAs, Proteases, Genetic Associations
Vol. 65 (2014), pp. 49–62More LessAbdominal aortic aneurysm (AAA) disease is a common, morbid, and highly lethal pathology. Extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of AAAs. Although surgery is highly effective in preventing death by rupture for larger AAAs, no guidance or preventive therapy is currently available for the >90% of patients whose aneurysms are below the surgical threshold. Predictive animal models of AAA as well as human pathological samples have revealed a complex circuit of AAA formation and progression. The proteolytic destruction of matrix components of the aorta by different proteases has been extensively studied over many years. Recently, a novel class of small noncoding RNAs, called microRNAs, was identified as “fine-tuners” of the translational output of target genes; they act by promoting mRNA degradation. Their therapeutic potential in limiting AAA development appears very intriguing. Further, current studies assessing genetic and heritable associations for AAA disease have provided great insight into its pathogenesis, potentially enabling us to better clinically manage affected patients.
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DNA Sequencing of Cancer: What Have We Learned?
Vol. 65 (2014), pp. 63–79More LessDNA sequencing has taught us much about the structure of cancer genomes and enabled the discovery of novel genes that drive and maintain tumorigenesis. With the advent and application of next-generation massively parallel sequencing technologies, one can rapidly generate and analyze data from the cellular “-omes”: genomes, exomes, and transcriptomes. This review highlights recent genomic discoveries in signal transduction, metabolism, epigenetic modifications, cell cycle and genome maintenance, RNA processing, and transcription. Additionally, genomic sequencing has revealed the complexity of the cancer genome and has enabled the discovery of functional rearrangements with therapeutic and diagnostic potentials.
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Applied Pharmacogenomics in Cardiovascular Medicine
Peter Weeke, and Dan M. RodenVol. 65 (2014), pp. 81–94More LessInterindividual heterogeneity in drug response is a central feature of all drug therapies. Studies in individual patients, families, and populations over the past several decades have identified variants in genes encoding drug elimination or drug target pathways that in some cases contribute substantially to variable efficacy and toxicity. Important associations of pharmacogenomics in cardiovascular medicine include clopidogrel and risk for in-stent thrombosis, steady-state warfarin dose, myotoxicity with simvastatin, and certain drug-induced arrhythmias. This review describes methods used to accumulate and validate these findings and points to approaches—now being put in place at some centers—to implementing them in clinical care.
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Molecular Testing in Breast Cancer
Vol. 65 (2014), pp. 95–110More LessTumor biomarker tests are critical to implementation of personalized medicine for patients at risk for or affected by breast cancer. A tumor biomarker test must have high analytical validity and clinical utility to be used to guide clinical care in standard practice. Few tumor biomarkers meet these high standards. These include germline DNA single-nucleotide polymorphisms in the BRCA1 and -2 genes to determine high risk in unaffected women, selected tissue-based markers to determine prognosis and predict benefit from therapy, and circulating MUC1, CEA and perhaps tumor cells to monitor patients with metastatic disease. Efforts to discover biomarkers that predict therapeutic toxicity are promising but not yet successful. Further research is needed to enhance the number of tumor biomarker tests so that patients with breast cancer can get the correct treatment at the appropriate time.
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Chemoprevention of Prostate Cancer
Vol. 65 (2014), pp. 111–123More LessLarge prospective randomized trials, such as the Prostate Cancer Prevention Trial (PCPT), Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, and Selenium and Vitamin E Cancer Prevention Trial (SELECT), have provided practitioners with considerable data regarding methods of treatment and prevention of prostate cancer. The best-studied medications for prevention are 5 alpha-reductase inhibitors. Their efficacy and side effects are well characterized. Other medications, dietary nutrients, and supplements have not been as well studied and generally do not demonstrate efficacy for disease prevention with an acceptable level of evidence.
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Thyroid Cancer
Vol. 65 (2014), pp. 125–137More LessThyroid cancer is rapidly increasing in incidence, but the mortality rate remains flat. Debate has arisen over the need to detect or treat most thyroid cancers early, given their favorable natural history. The appropriate extent of surgery for thyroid cancer is also controversial: some researchers advocate partial and others total thyroidectomy; some advocate prophylactic central cervical lymph node dissection, whereas others only rarely recommend lymphadenectomy. Although radioactive iodine is effective, its appropriate use and dosage remain controversial. In addition, molecular analysis of thyroid cancer is frequently used for diagnostic purposes involving preoperative fine-needle biopsy specimens as well as to define targetable pathways altered in the disease to guide clinical trials of drug therapy for advanced thyroid cancers.
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Targeting Apoptosis Pathways for New Cancer Therapeutics
Vol. 65 (2014), pp. 139–155More LessThe past decade has witnessed tremendous advances in the discovery and development of novel small-molecule inhibitors targeting apoptosis pathways for cancer treatment, with some compounds now in clinical development. Early promising clinical data have been reported with these new classes of anticancer drugs. This review highlights the recent advancements in the development of small-molecule inhibitors targeting three major classes of antiapoptotic proteins: antiapoptotic B cell lymphoma 2 (BCL-2) proteins, inhibitor of apoptosis proteins (IAPs), and murine double-minute 2 (MDM2). Special emphasis is given to those that have been advanced into clinical trials. The challenges and future directions in the further preclinical and clinical development of these new anticancer drugs are also discussed.
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Targeting Metabolic Changes in Cancer: Novel Therapeutic Approaches
Vol. 65 (2014), pp. 157–170More LessTherapeutic strategies designed to target cancer metabolism are an area of intense research. Antimetabolites, first used to treat patients in the early twentieth century, served as an early proof of concept for such therapies. We highlight strategies that attempt to improve on the anti-metabolite approach as well as new metabolic drug targets. Some of these targets have the advantage of a strong genetic anchor to drive patient selection (isocitrate dehydrogenase 1/2, Enolase 2). Additional approaches described here derive from hypothesis-driven and systems biology efforts designed to exploit tumor cell metabolic dependencies (fatty acid oxidation, nicotinamide adenine dinucleotide synthesis, glutamine biology).
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Retinoblastoma: Saving Life with Vision
Vol. 65 (2014), pp. 171–184More LessRetinoblastoma has gone from >95% mortality to >95% survival in the past 100 years. Once enucleation techniques were perfected, the majority of children survived, but without the eye (or vision in that eye). Over the past 100 years, progressively better techniques have been developed for salvaging vision without sacrificing patient survival. Presently, 99% of children treated at our center survive their cancer, >99% retain at least one eye, and >90% retain normal vision in at least one eye. The introduction of ophthalmic artery chemosurgery has been the most dramatic, non-radiation-based mode to maximally preserve vision.
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Immune Modulation in Cancer with Antibodies
Vol. 65 (2014), pp. 185–202More LessIpilimumab is the prototypical immunomodulatory antibody, approved by the FDA in 2011 for advanced melanoma on the basis of survival benefit. Since that time, we have made significant strides in optimizing this therapy: we have characterized the spectrum of immune-related adverse events and learned how to mitigate them with treatment algorithms, discovered potential biomarkers of activity, and identified the potential synergy between checkpoint modulation and other therapeutic modalities. Recent phase I trials have established the efficacy and safety of next-generation checkpoint agents, including PD-1 and PD-L1 inhibitors, across multiple tumor types. Much work lies ahead in developing these next-generation checkpoint agents, testing them in combination, and determining how to integrate them into the treatment paradigms of various tumor types.
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Depression as a Risk Factor for Cancer: From Pathophysiological Advances to Treatment Implications
Vol. 65 (2014), pp. 203–221More LessInnate immune activation and inflammation have been posited to play a role in the pathophysiology of both depression and neoplastic growth. Cancer patients experience a threefold higher rate of depression than the general population within the first five years of diagnosis. Chronic depression is associated with increased cancer risk and shortened survival. Although the precise cellular and molecular mechanisms of this bidirectional relationship remain unclear, elevated concentrations of circulating plasma proinflammatory cytokines associated with depression may mediate the neuroendocrine, neural, and immune pathways that account for the relationship. Proinflammatory cytokines, in turn, are known to modulate key neurobiological correlates of depression including hypothalamic-pituitary-adrenal (HPA) axis dysregulation, monoamine neurotransmitter metabolism, and limbic system activity. Research is needed to determine whether optimal depression treatment improves cancer survival and to develop antidepressant strategies that target molecular and cellular mechanisms mediating inflammation and the neurobiological pathways influenced by the proinflammatory cytokines.
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IL-1 Blockade in Autoinflammatory Syndromes1
Vol. 65 (2014), pp. 223–244More LessMonogenic autoinflammatory syndromes present with excessive systemic inflammation including fever, rashes, arthritis, and organ-specific inflammation and are caused by defects in single genes encoding proteins that regulate innate inflammatory pathways. Pathogenic variants in two interleukin-1 (IL-1)–regulating genes, NLRP3 and IL1RN, cause two severe and early-onset autoinflammatory syndromes, CAPS (cryopyrin associated periodic syndromes) and DIRA (deficiency of IL-1 receptor antagonist). The discovery of the mutations that cause CAPS and DIRA led to clinical and basic research that uncovered the key role of IL-1 in an extended spectrum of immune dysregulatory conditions. NLRP3 encodes cryopyrin, an intracellular “molecular sensor” that forms a multimolecular platform, the NLRP3 inflammasome, which links “danger recognition” to the activation of the proinflammatory cytokine IL-1β. The success and safety profile of drugs targeting IL -1 in the treatment of CAPS and DIRA have encouraged their wider use in other autoinflammatory syndromes including the classic hereditary periodic fever syndromes (familial Mediterranean fever, TNF receptor–associated periodic syndrome, and hyperimmunoglobulinemia D with periodic fever syndrome) and additional immune dysregulatory conditions that are not genetically well defined, including Still's, Behcet's, and Schnitzler diseases. The fact that the accumulation of metabolic substrates such as monosodium urate, ceramide, cholesterol, and glucose can trigger the NLRP3 inflammasome connects metabolic stress to IL-1β-mediated inflammation and provides a rationale for therapeutically targeting IL-1 in prevalent diseases such as gout, diabetes mellitus, and coronary artery disease.
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α7-Nicotinic Acetylcholine Receptor Agonists for Cognitive Enhancement in Schizophrenia
Vol. 65 (2014), pp. 245–261More Lessα7-Nicotinic acetylcholine receptors have emerged as a potential therapeutic target for the treatment of neurocognitive dysfunctions in schizophrenia that are often resistant to existing antipsychotic drugs. Molecular evidence for involvement in schizophrenia of CHRNA7, the gene for the receptor subunit, in the neurobiology of deficits in attention is a critical rationale for the clinical study of α7-nicotinic receptor agonists to improve neurocognition. Initial clinical trials show enhancement of inhibitory neuron function related to sensory gating and increased attention and working memory, as well as improvement in negative symptoms such as anhedonia and alogia. Further development of this therapeutic strategy requires assessment of interactions with patients' heavy cigarette smoking and the relationship of this mechanism to the therapeutic effects of clozapine and olanzapine, both highly effective therapeutics with significant side effects.
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Anti–B Cell Antibody Therapies for Inflammatory Rheumatic Diseases
Vol. 65 (2014), pp. 263–278More LessSeveral monoclonal antibodies targeting B cells have been tested as therapeutics for inflammatory rheumatic diseases. We review important observations from randomized clinical trials regarding the efficacy and safety of anti–B cell antibody-based therapies for rheumatoid arthritis, systemic lupus erythematosus, antineutrophil cytoplasmic antibody-associated vasculitis, polymyositis/dermatomyositis, and primary Sjögren's syndrome. For some anti–B cell agents, clinical benefits have been convincingly demonstrated, while other B cell–targeted therapies failed to improve outcomes when added to standard-of-care treatment or were associated with increased rates of adverse events. Although the risk-benefit balance seems to be acceptable for currently licensed anti–B cell agents, additional studies are required to fully assess the safety of treatment regimens involving prolonged interference with B cell counts and functions in rheumatic disorders. Future studies should also evaluate how to maintain disease control by means of conventional and/or biologic immunosuppressants after remission-induction with anti–B cell antibodies.
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Nuclear Receptor Coactivators: Master Regulators of Human Health and Disease
Vol. 65 (2014), pp. 279–292More LessTranscriptional coregulators (coactivators and corepressors) have emerged as the principal modulators of the functions of nuclear receptors and other transcription factors. During the decade since the discovery of steroid receptor coactivator-1 (SRC-1), the first authentic coregulator, more than 400 coregulators have been identified and characterized, and deciphering their function has contributed significantly to our understanding of their role in human physiology. Deregulated expression of coregulators has been implicated in diverse disease states and related pathologies. The advancement of molecular technologies has enabled us to better characterize the molecular associations of the SRC family of coactivators with other protein complexes in the context of gene regulation. These continuing discoveries not only expand our knowledge of the roles of coactivators in various human diseases but allow us to discover novel coactivator-targeting strategies for therapeutic intervention in these diseases.
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Male Circumcision: A Globally Relevant but Under-Utilized Method for the Prevention of HIV and Other Sexually Transmitted Infections
Vol. 65 (2014), pp. 293–306More LessRandomized trials have demonstrated that male circumcision (MC) reduces heterosexual acquisition of HIV, herpes simplex virus type 2, human papillomavirus (HPV), and genital ulcer disease among men, and it reduces HPV, genital ulcer disease, bacterial vaginosis, and trichomoniasis among female partners. The pathophysiology behind these effects is multifactorial, relying on anatomic and cellular changes. MC is cost effective and potentially cost saving in both the United States and Africa. The World Health Organization and Joint United Nations Program on HIV/AIDS proposed reaching 80% MC coverage in HIV endemic countries, but current rates fall far behind targets. Barriers to scale-up include supply-side and demand-side challenges. In the United States, neonatal MC rates are decreasing, but the American Academy of Pediatrics now recognizes the medical benefits of MC and supports insurance coverage. Although MC is a globally valuable tool to prevent HIV and other sexually transmitted infections, it is underutilized. Further research is needed to address barriers to MC uptake.
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New Frontiers in Patient-Reported Outcomes: Adverse Event Reporting, Comparative Effectiveness, and Quality Assessment
Vol. 65 (2014), pp. 307–317More LessPatient-reported outcomes (PROs) are data elements directly reported by patients or their surrogates about experiences with care, including symptoms, functional status, or quality of life. PROs have commonly been evaluated in clinical trials for drug and medical device development. Interest is growing in the ability to integrate PROs into additional contexts, particularly product safety evaluation, comparative effectiveness research, and measurement of care quality. This interest reflects a growing focus on patient-centeredness in health care broadly and on provisions of the US Patient Protection and Affordable Care Act of 2010. Multiple initiatives demonstrate the feasibility and value of patient reporting in these areas. Inclusion of PROs in electronic health records and hospital patient portals, as well as longitudinal registries, can facilitate use of these data for multiple analytic purposes as well as enhance delivery of care and patient-provider communication. Challenges include the logistics and cost of implementing PRO programs; missing data, particularly from hard-to-reach and ill patients; and the need for standardization of outcome measures and electronic data representation. These challenges have been surmounted in limited initiatives and now must be translated to larger implementations.
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Evidence-Based Treatment of Post-Traumatic Stress Disorder
Vol. 65 (2014), pp. 319–332More LessThe term translational research is typically used to refer both to “bench to bedside” research, in which preclinical research findings inform the development of novel therapeutics, and to the dissemination of new treatments to the community to encourage the use of the new health practices and treatments. Both definitions are germane to understanding the evidence base for treatment of post-traumatic stress disorder (PTSD) today. This article offers (a) an overview of evidence-based treatments for PTSD, (b) a description of a translational model of PTSD, and (c) a discussion of common barriers to dissemination and implementation of the empirically validated treatments. Recent studies in the field are discussed with a focus on pharmacotherapies, psychotherapies, and combined treatments.
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Chimeric Antigen Receptor Therapy for Cancer
Vol. 65 (2014), pp. 333–347More LessImproved outcomes for patients with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, synthetic biology, and cell-processing technologies has paved the way for clinical applications of chimeric antigen receptor–based therapies. This new form of targeted immunotherapy merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity and long-term persistence provided by cytotoxic T cells. Although this field is still in its infancy, clinical trials have already shown clinically significant antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B cell lymphoma, and trials targeting a variety of other adult and pediatric malignancies are under way. Ongoing work is focused on identifying optimal tumor targets and on elucidating and manipulating both cell- and host-associated factors to support expansion and persistence of the genetically engineered cells in vivo. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of cancer.
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Renal Sympathetic Denervation for the Treatment of Refractory Hypertension
Vol. 65 (2014), pp. 349–365More LessResistant hypertension poses significant health concerns. There are strong demands for new and safe therapies to control resistant hypertension while addressing its common causes, specifically poor compliance to lifelong polypharmacy, lifestyle modifications, and physician inertia. The sympathetic nervous system plays a significant pathophysiological role in hypertension. Surgical sympathectomy for blood pressure reduction is an old but extremely efficacious therapeutic concept, now abandoned with the dawn of a safer contemporary pharmacology era. Recently, clinical studies have revealed promising results for safe and sustained blood pressure reduction with percutaneous renal sympathetic denervation. This is a novel, minimally invasive, device-based therapy, specifically targeting and ablating the renal artery nerves with radiofrequency waves without permanent implantation. There are also reported additional benefits in related comorbidities, such as impaired glucose metabolism, renal impairment, left ventricular hypertrophy, heart failure, and others. This review focuses on how selective renal sympathetic denervation works, its present and potential therapeutic indications, and its future directions.
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Transcatheter Aortic Valve Replacement: Game-Changing Innovation for Patients with Aortic Stenosis
Vol. 65 (2014), pp. 367–383More LessTranscatheter aortic valve replacement (TAVR) is an emerging technology for the management of patients with severe aortic stenosis (AS). First reported in 2002, TAVR has made remarkable progress in the past decade with completion of major randomized clinical trials, multiple observational registries, and evolution of several new devices. This article is a brief introductory overview of the TAVR procedure, devices, trials and registries, and newer developments in the field.
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Future of Cholesteryl Ester Transfer Protein Inhibitors
Vol. 65 (2014), pp. 385–403More LessThe cholesteryl ester transfer protein (CETP) plays an integral role in the metabolism of plasma lipoproteins. Despite two failures, CETP inhibitors are still in clinical development. We review the genetics of CETP and coronary disease, preclinical data on CETP inhibition and atherosclerosis, and the effects of CETP inhibition on cholesterol efflux and reverse cholesterol transport. We discuss the two failed CETP inhibitors, torcetrapib and dalcetrapib, and attempt to extract lessons learned. Two CETP inhibitors, anacetrapib and evacetrapib, are in phase III development, and we attempt to differentiate them from the failed drugs. Whether pharmacologic CETP inhibition will reduce the risk of cardiovascular disease is one of the most fascinating and important questions in the field of cardiovascular medicine.
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Adaptive Clinical Trial Design
Vol. 65 (2014), pp. 405–415More LessIn recent years, the use of adaptive design methods in clinical trials based on accumulated data at interim has received much attention because of its flexibility and efficiency in pharmaceutical/clinical development. In practice, adaptive design may provide the investigators a second chance to modify or redesign the trial while the study is still ongoing. However, it is a concern that a shift in target patient population may occur after significant adaptations are made. In addition, the overall type I error rate may not be preserved. Moreover, the results may not be reliable and hence are difficult to interpret. As indicated by the US Food and Drug Administration draft guidance on adaptive design clinical trials, the adaptive design has to be a prospectively planned opportunity and should be based on information collected within the study, with or without formal statistical hypothesis testing. This article reviews the relative advantages, limitations, and feasibility of commonly considered adaptive designs in clinical trials. Statistical concerns when implementing adaptive designs are also discussed.
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Reduction of Low-Density Lipoprotein Cholesterol by Monoclonal Antibody Inhibition of PCSK9
Vol. 65 (2014), pp. 417–431More LessPublished phase I and II trials with two fully human monoclonal antibodies to PCSK9 have provided comprehensive evidence that inhibiting PCSK9 is a very effective method to reduce low-density lipoprotein cholesterol (LDL-C). In all populations studied so far, whether on statins or LDL-C-reducing diet alone, with or without a genetic defect in the LDL receptor, and in subjects intolerant to statins, the LDL-C reductions have been large and consistent. Even the most efficacious statin, rosuvastatin, at its highest dose has not achieved such reductions. The clinical trials have established that monoclonal antibody therapy targeted to PCSK9 may be administered subcutaneously every two or four weeks. Current data suggest these drugs will provide an effective therapeutic option for LDL-C reduction and that, if proven safe in phase III trials, they will be as important to LDL-C control, and likely to cardiovascular disease risk reduction, as statins have been over the past three decades.
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The Antithrombotic Effects of Statins
Vol. 65 (2014), pp. 433–445More LessHypercholesterolemia is considered the primary risk factor for cardiovascular disease. An estimated 200 million prescriptions are issued per year for statins to treat hypercholesterolemia. Importantly, statins have additional beneficial effects independent of their effects on lipids. Recent studies have shown that statins reduce thrombosis via multiple pathways, including inhibiting platelet activation and reducing the pathologic expression of the procoagulant protein tissue factor. Many of the antithrombotic effects of statins are attributed to inhibiting prenylation of RhoA and effects on other intracellular signaling molecules such as NF-κB and KLF2. These antithrombotic activities of statins likely contribute to the ability of statins to reduce the incidence of cardiovascular death.
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Delivering Value: Provider Efforts to Improve the Quality and Reduce the Cost of Health Care
Vol. 65 (2014), pp. 447–458More LessGrowing concern regarding costs of care and health outcomes in the United States has led to widespread calls to address the issue of health care spending. Today, providers across the country are working both to improve the quality and to reduce the cost of health care. These activities span multiple care delivery settings and include care standardization and redesign, shared decision making, palliative care, care coordination, readmission reduction, patient engagement, predictive modeling, and direct cost reduction. These efforts differ from those undertaken in the past because of the availability of information technology tools to collect and analyze data, and because of the emphasis on cost reduction in conjunction with quality improvement. Although the available literature reflects only a small fraction of the provider activities currently in progress, there is cause for hope for achieving a sustainable, innovative, and value-driven health care system.
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New Cost-Effective Treatment Strategies for Acute Emergency Situations
Vol. 65 (2014), pp. 459–469More LessIn an era of ever-increasing healthcare costs, new treatments must not only improve outcomes and quality of care but also be cost-effective. This is most challenging for emergency and critical care. Bigger and better has been the mantra of Western medical care for decades, leading to costlier but not necessarily better care. Recent advances focused on new implementation processes for evidence-based best practices such as checklists and bundles have transformed medical care. We outline recent advances in medical practice that have positively affected both the quality of care and its cost-effectiveness. Future medical care must be smarter and more effective if we are to meet the increasing demands of an aging patient population in the context of ever more limited resources.
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Reducing Hospital Readmission Rates: Current Strategies and Future Directions
Vol. 65 (2014), pp. 471–485More LessNew financial penalties for institutions with high readmission rates have intensified efforts to reduce rehospitalization. Several interventions that involve multiple components (e.g., patient needs assessment, medication reconciliation, patient education, arranging timely outpatient appointments, and providing telephone follow-up) have successfully reduced readmission rates for patients discharged to home. The effect of interventions on readmission rates is related to the number of components implemented; single-component interventions are unlikely to reduce readmissions significantly. For patients discharged to postacute care facilities, multicomponent interventions have reduced readmissions through enhanced communication, medication safety, advanced care planning, and enhanced training to manage medical conditions that commonly precipitate readmission. To help hospitals direct resources and services to patients with greater likelihood of readmission, risk-stratification methods are available. Future work should better define the roles of home-based services, information technology, mental health care, caregiver support, community partnerships, and new transitional care personnel.
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Previous Volumes
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Volume 75 (2024)
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Volume 74 (2023)
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Volume 73 (2022)
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Volume 72 (2021)
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Volume 71 (2020)
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Volume 70 (2019)
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Volume 69 (2018)
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Volume 68 (2017)
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Volume 67 (2016)
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Volume 66 (2015)
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Volume 65 (2014)
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Volume 64 (2013)
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Volume 63 (2012)
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Volume 62 (2011)
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Volume 61 (2010)
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Volume 60 (2009)
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Volume 59 (2008)
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Volume 58 (2007)
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Volume 57 (2006)
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Volume 56 (2005)
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Volume 55 (2004)
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Volume 54 (2003)
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Volume 53 (2002)
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Volume 52 (2001)
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Volume 51 (2000)
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Volume 50 (1999)
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Volume 49 (1998)
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Volume 48 (1997)
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Volume 47 (1996)
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Volume 46 (1995)
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Volume 45 (1994)
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Volume 44 (1993)
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Volume 43 (1992)
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Volume 42 (1991)
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Volume 41 (1990)
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Volume 40 (1989)
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Volume 39 (1988)
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Volume 38 (1987)
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Volume 37 (1986)
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Volume 36 (1985)
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Volume 35 (1984)
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Volume 34 (1983)
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Volume 33 (1982)
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Volume 32 (1981)
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Volume 31 (1980)
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Volume 30 (1979)
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Volume 29 (1978)
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Volume 28 (1977)
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Volume 27 (1976)
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Volume 26 (1975)
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Volume 25 (1974)
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Volume 24 (1973)
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Volume 23 (1972)
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Volume 22 (1971)
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Volume 21 (1970)
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Volume 20 (1969)
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Volume 19 (1968)
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Volume 18 (1967)
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Volume 17 (1966)
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Volume 16 (1965)
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Volume 15 (1964)
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Volume 14 (1963)
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Volume 13 (1962)
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Volume 12 (1961)
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Volume 11 (1960)
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Volume 10 (1959)
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Volume 9 (1958)
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Volume 8 (1957)
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Volume 7 (1956)
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Volume 6 (1955)
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Volume 5 (1954)
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Volume 4 (1953)
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Volume 3 (1952)
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Volume 2 (1951)
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Volume 1 (1950)
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Volume 0 (1932)