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Prepared by the National Institute of Arthritis and Musculoskeletal and Skin Diseases
December 22, 2015

Chapter 1: Etiology and Prevention

Chapter 2: Mechanisms of Disease

Chapter 3: New Treatments and Interventions

Chapter 4: Diagnosis and Clinical Care

Chapter 5: Behavioral, Biopsychosocial and Health Services Research

Chapter 6: Special Populations

Chapter 7: Training and Collaborations

Appendix 1: Overview of the Development Process
Appendix 2: Requests for Information Published in the NIH Guide For Grants and Contracts
Appendix 3: Webinar Participants
Appendix 4: Staff Acknowledgements

Systemic lupus erythematosus (SLE, or lupus) is one of more than 80 known autoimmune diseases. An autoimmune disease is one in which the body's immune system—its normal defense against harmful invaders including viruses and bacteria—turns its attack against the body's own organs, tissues, and cells. In some autoimmune diseases, the target of the attack is limited to a particular part of the body—the blood vessels, moisture-producing glands of the eyes and mouth, or insulin-producing cells of the pancreas, for example. In lupus, the attack is systemic, meaning it affects many organs and organ systems including the skin, joints, heart, lungs, kidneys, and brain. The results can be disabling or even deadly.

Disease activity often waxes and wanes. Periods of relatively mild disease may be followed by flares, or periods of increased disease activity involving one or more organ systems, which can lead to irreversible organ damage. Some flares are evident through clinical symptoms such as a skin rash, increased fatigue, joint inflammation, oral or nasal ulcers, or seizures. In other cases, the only evidence of a flare is a laboratory test showing a low white blood cell or platelet count or protein in the urine, for example.

By the most conservative estimates, there are at least 322,000 Americans with definite or probable lupus.1 Recent independent surveys have suggested a prevalence as high as 1.5 million.1 Women with the disease outnumber men nine to one. Lupus often strikes women in their early working and childbearing years, interfering with the ability to work, have or raise a family, or in some cases, even care for themselves.

1 CDC Arthritis Lupus

The most heterogeneous of the autoimmune diseases, lupus is also one of the most difficult to understand and treat. Sixty years ago, about 50 percent of those with lupus died within five years of their diagnosis. Today, thanks to advances brought about by research, 97 percent of lupus patients are living five years after diagnosis, and 90 percent continue to survive after 10 years. The transformation of lupus from a disease with a high mortality rate to one that is chronic has led to an increased need for better therapies that can manage long-term symptoms. Ongoing research is likely to lead to new therapies with fewer side effects.

The past two decades of research have yielded a wealth of new information and extraordinary growth in improving our understanding of lupus. As a result, opportunities now exist to identify potential genetic, epigenetic, environmental, and infectious causes of lupus, and to develop novel approaches for lupus treatment and prevention. To achieve these goals, the National Institutes of Health (NIH) places a high priority on cross-disciplinary research and the participation of other government agencies and private organizations in these efforts.

To facilitate collaboration among the NIH Institutes, other federal agencies, voluntary and professional organizations, and industry groups that have an interest in lupus, the NIH established the Lupus Federal Working Group (LFWG) in 2003 at the request of Congress. The LFWG is led by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and includes representatives from all relevant Department of Health and Human Services (HHS) agencies and other federal departments having an interest in lupus. This includes the National Institute of Allergy and Infectious Diseases; the National Institute of Neurological Disorders and Stroke; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Heart, Lung, and Blood Institute; the NIH Office of Research on Women's Health; and other agencies of the federal government, including the HHS Office on Women’s Health, the U.S. Food and Drug Administration (FDA), and the Centers for Disease Control and Prevention (CDC). Voluntary organizations and representatives from the private sector also attend and participate in the meetings of the LFWG.

In fiscal year 2005, the House Appropriations Committee directed the NIH to develop a plan to guide the nation's investment in lupus research. To identify the opportunities, priorities and needs in lupus research that should be considered for inclusion in the plan, the NIH convened a workshop with scientific experts. The highlights of their conclusions were reported in 2007 in The Future Directions of Lupus Research.

In July 2014, the Congressional Lupus Caucus requested that the NIAMS, as convener of the LFWG, develop a new coordinated action plan for lupus research on behalf of the NIH. Over the next year, the Institute issued two Requests for Information to solicit comments from the public, and held a webinar with external experts and lupus groups to obtain input on research directions that should be included in the coordinated Action Plan. A detailed description of the development of this plan is provided in Appendix 1. This document represents a synthesis of internal and external input on promising future directions for lupus research. It will help to inform priority-setting processes among all lupus-related organizations and serve as a guide for investigators as they develop independent approaches to address the numerous scientific opportunities in lupus.

Through the development process, four key questions emerged.

  • First, is lupus one disease or many? In recent years, new research tools have improved the molecular characterization of lupus, providing support for the view that lupus actually represents a spectrum of related, but distinct, conditions. Many of the suggested research directions described in this plan will help researchers identify and define subgroups in a clinically meaningful way. If lupus represents a collection of related diseases, it will be important to determine whether these diseases have different causes and mechanisms that would require distinct prevention and treatment strategies. It also will have important implications for the grouping of patients participating in observational and interventional clinical trials.
  • Second, how can new and emerging research tools and technologies advance our understanding of disease mechanisms? Many contributors to the plan expressed enthusiasm about the potential for cutting-edge tools (e.g., genetic analysis and gene editing, high-throughput and systems biology approaches, state-of-the-art imaging modalities, and mobile technologies) to move research forward. The research tools developed in recent years will enable scientists to explore disease mechanisms and follow patients clinically in ways that have not been possible previously.
  • Third, how can we facilitate the development of new and emerging treatment paradigms? Since 2007, when the last plan was published, researchers have made tremendous progress in identifying individuals who are at-risk for lupus, as well as molecular markers that appear before the onset of clinical symptoms. Researchers now hope to translate such discoveries into strategies for early intervention or even disease prevention. For individuals with established lupus, researchers are focused on designing new trials that could test emerging candidate drugs in combination or sequentially with existing therapies.
  • Finally, how can various sectors work together to more effectively conduct and support lupus research and research training? Many members of the community have highlighted the need for innovative partnerships between federal agencies, patient and professional groups, and industry. For example, novel partnerships could advance the goal of precision medicine—an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle—for people with lupus.
  • This research plan highlights many opportunities to increase our understanding of lupus at the molecular, individual, and population levels, which should ultimately allow the translation of new knowledge into safer and more effective treatments and, eventually, curative strategies. The report is organized to mirror current understanding of the disease, and to reflect opportunities for advancement. It supplements and enhances ongoing plans and activities of the NIH, such as the NIAMS Long Range Plan (2015-2019), as well as the work of the LFWG and the NIH Autoimmune Diseases Coordinating Committee.

Chapter 1: Etiology and Prevention

Although the cause of lupus remains unknown, there is strong evidence that genetics, epigenetics, environmental, and infectious and non-infectious factors play a role. New ideas, concepts and technologies have improved understanding of the factors that may predispose people to lupus and trigger its development and clinical course. Scientists' perseverance in gathering biospecimens and clinical histories from lupus patients and their relatives has opened new research avenues. Emerging opportunities to study genes and pathways, epigenetics, and gene-environment interactions are expected to improve understanding of lupus initiation and progression, and ultimately lead to development of better tools for diagnosis, prognosis, prevention, and treatment.

NIH-supported research has been key in the discovery of potential factors that influence susceptibility to lupus. Since the publication of the original Future Directions of Lupus Research report in 2007, researchers have made substantial advances related to understanding the etiology of lupus. Genome-wide association studies have identified numerous genetic variants associated with lupus, although the functions of identified variants and their contribution to disease remain largely unknown. In most cases, lupus is thought to be caused by a combination of many genetic variations, each with modest effects, although recent studies have pointed to the existence of rare variations with more substantial effects in certain lupus patient subsets. Research on genetic variants and the mechanisms by which they affect disease initiation and progression can provide new insights into lupus pathogenesis.

While genetics may play a crucial role in the development of lupus, researchers agree that environmental factors contribute to disease initiation and progression in genetically susceptible individuals. Recent data suggest that environmental factors may directly influence disease risk by interacting with the genome to alter gene expression. Analyses of gene-environment interactions are expected to provide information about the role of epigenetic alterations (e.g., DNA methylation patterns in T cells), chromatin remodeling, RNA transcripts and their encoded proteins, and microRNAs in lupus. Research on genes or variants that interact with certain environmental factors (e.g., gut microbes, dietary components, infectious agents) to trigger disease may provide important insights into lupus development, progression, and severity.

Research Objectives

Broad areas of potential research directions include:

Genetics and Genomics

  • Investigate the genetic architecture that influences susceptibility to autoimmune diseases.
  • Investigate the potential role of epistatic interactions between multiple lupus susceptibility genes in a single individual.
  • Use bioinformatics tools to identify new genetic variants and target pathways in lupus.
  • Identify and determine the function of causal variants within lupus-associated genetic elements.
  • Use in vivo models to determine the effects of identified risk variants and their relative contributions to autoimmunity and disease.
  • Use induced pluripotent stem cell (iPSC) or genomic editing technologies to improve our understanding of lupus risk and its preclinical stages.
  • Characterize epigenomic events in specific cell types and subtypes from individuals with and without defined risk genotypes to understand the effects of epigenetic alterations within the context of known genomic variants.
  • Conduct studies in well-defined longitudinal patient cohorts so that changes in -omics readouts can be linked to phenotypic alterations.
  • Conduct whole exome or genome sequencing to define extreme human phenotypes of lupus, and to identify somatic mutations in critical cell populations in humans and in animal models of lupus.
  • Use molecular phenotyping to facilitate studies of etiology and disease mechanisms by identifying molecular signatures that can be used to stratify heterogeneous groups of patients into more homogeneous populations.

  • Investigate the contribution of environmental factors (e.g., diet, lifestyle, human microbiome) to risk of developing lupus or developing flares in individuals with established lupus.
  • Understand the mechanisms by which exposure to sunlight may trigger lupus symptoms.
  • Investigate factors that may be associated with lupus flares, such as ultraviolet (UV) light, stress, medications, physical activity, sleep deprivation, and infections (viral or other).
  • Investigate maternal (pre-conception or gestational) and early-childhood exposures that may alter the risk of development of lupus in children.
  • Use detailed epidemiologic studies and proteomic analyses to clearly identify signatures of prior microbial or other environmental exposures.
  • Foster collaboration between environmental experts and clinical investigators to better assess and measure relevant exposures using emerging new tools such as wearable biosensors.
  • Link potential environmental exposures to molecular disease mechanisms (e.g., epigenetic changes, Toll-like receptor triggering, NETosis, other pathways).
  • Understand the interplay between genetics and environment in the development of lupus.
    • Understand how environmental factors may cause epigenetic changes in critical cell types (e.g., T cell DNA methylation).
    • Study the impact of environmental factors that cause oxidative stress.
  • Differentiate disease-causing genetic and environmental factors from those that affect disease propagation and events in later-stage disease, such as chronic tissue damage.

  • Conduct longitudinal studies of patients as they develop lupus, including collecting biological specimens and clinical data, in order to understand disease initiation and identify exposures related to the development of lupus.
  • Investigate time windows of increased vulnerability or susceptibility to the development of lupus (e.g., in utero, early childhood, adolescence, or adulthood).
  • Understand the molecular factors that influence age of onset of lupus.
  • Leverage the expansion of insurance coverage and electronic medical record data availability to enhance epidemiological studies, potentially including geographic exposure, medication, and healthcare utilization data.
  • Leverage the availability of data from social networking and biometric wearables to enhance epidemiological studies to include environmental factors and the patient voice and experience.
  • Study changes in lupus prevalence and incidence over time across the age-spectrum of disease.

Chapter 2: Mechanisms of Disease

To lay the groundwork for future therapies, researchers are studying the altered biological processes that lead to the wide array of immune system abnormalities that characterize lupus. Recent findings suggest that both arms of the immune system—the innate and adaptive immune systems—are involved in the disease, and various interplays between the two systems may result in the initiation and propagation of autoimmunity. Over the past few years, researchers have learned more about the role of Toll-like receptors (TLRs) and other innate immune system receptors in lupus pathogenesis. They also have improved understanding of immune cell subsets (e.g., T cell subsets, B cell subsets, dendritic cells) and their signaling pathways. Other work has shed light on the role of neutrophils, an abundant, yet short-lived white blood cell involved in the innate immune response, in lupus. For example, recent studies have indicated that neutrophil death by a mechanism called NETosis likely provides cellular material that may elicit an autoimmune response.

Although immune dysregulation plays a major role in lupus, structural and functional properties of target organs (kidneys, heart, lungs, blood vessels and brain) may contribute significantly to the development of tissue damage and clinical manifestations. Recent advances indicate that target organ processes may be related to the induction and maintenance of damage, including expression of proteins related to organ function. Researchers have begun to increase their focus on autoantigens in target tissues, local immune responses in target organ tissue, and the role of molecular pathways within resident tissue cells in organ damage. This is particularly relevant in lupus nephritis, which is at least as severe in males as it is in females, suggesting that the molecular pathways involved in renal damage must be aggressive in both sexes. In the past few years, researchers have gained a better understanding of the mechanisms of accelerated atherosclerosis in lupus and have learned more about how interferon-alpha damages blood vessels. By better understanding mechanisms of organ damage in lupus, researchers can test approaches to modify these processes, and perhaps minimize or prevent some of the most serious complications of the disease.

Research Objectives

Broad areas of potential research directions include:

Immune and Inflammatory Mechanisms

  • Understand the contribution of dysregulated cellular processes (e.g., cell death, defective clearance of dead cells, autophagy, oxidative stress) in development and progression of lupus.
  • Elucidate the role of viruses, hormones, systemic inflammation and other factors as disease initiators or triggers of disease flares.
  • Understand the biological basis for sex differences in immune and inflammatory systems that contribute to the sex differences in lupus.
  • Understand the relative roles of membrane bound and cytosolic innate immune sensors and their signaling pathways and triggers on the initiation and pathogenesis of lupus; identify critical steps that can be targeted for therapy.
  • Explore the role of gene-regulatory elements, such as transcription factors, enhancers/super-enhancers, and microRNAs on the regulation of cellular functions related to lupus.
  • Study the innate and adaptive immune responses to endogenous retroelements (i.e., viral nucleic acids embedded in the genome), in both animal models and humans.
  • Characterize immune cell tolerance defects in lupus, including regulatory cells (e.g., Treg cells, Breg cells) and other immune-dampening systems that may be altered in lupus.
  • Investigate methods to induce tolerance, potentially through peptide vaccination.
  • Elucidate the role of the major histocompatibility complex locus and its related functions in lupus susceptibility and initiation.
  • Define the factors and mechanisms that cause autoantibody specificity (e.g., why do some patients develop antibodies to anti-DNA leading to glomerulonephritis, while others develop antibodies to red blood cells leading to autoimmune hemolytic anemia?).
  • Understand the regulation and contribution of different B cell populations to lupus pathogenesis, and develop models to track the generation and progression of autoreactive B cells.
  • Explore new methods to target autoreactive B cells and plasma cells (e.g., therapeutic targeting of nuclear export proteins) in lupus.
  • Continue to use emerging technologies (e.g., CRISPR) to create new animal models with lupus genotype alleles; replicate these studies in human cell lines.
  • Understand the role of the microbiome in autoimmune disease initiation and progression, and how manipulation of the microbiome may alter disease course, in both humans and lupus animal models.
  • Identify markers and pathogenic pathways activated in patients with early/pre-clinical disease versus those with established disease and those in remission.
  • Understand disease-triggering immunological mechanisms in people who have a high risk for lupus or in patients with non-specific early symptoms of potential lupus.
  • Understand specific elements of the interferon-alpha signature that associate with disease severity, poor prognosis, or response to therapy.
  • Differentiate distinct molecular pathways that might separate what we now define as lupus on clinical grounds into distinct biological diseases that can be studied individually.
  • Understand the mechanisms that link complement deficiencies to the development of lupus.
  • Investigate the role of glycans in blood and vascular systems leading to immune dysregulation in lupus.

Target Organ Damage

  • Study the biological basis for sex differences in target organs and tissues that contribute to the sex differences in lupus.
  • Understand physiological mechanisms and risk factors of renal damage.
    • Elucidate mechanisms of renal injury, progression, and recovery.
    • Understand the role of autoantibodies and immune complexes in the pathogenesis of kidney injury.
  • Determine whether animal models can be developed for membranous lupus nephritis.
  • Apply brain imaging techniques and clinical assessment tools (e.g., NIH Toolbox) to explore central nervous system lupus
  • Investigate the contribution of cytokines and autoantibodies to the various presentations of neuropsychiatric lupus, including cognitive dysfunction.
  • Investigate the effects of interactions between components of the immune system on metabolism in lupus, as well as on traditional cardiovascular risk factors, such as premature atherosclerosis.
  • Understand the connection between cardiovascular disease in lupus and immune dysregulation.
  • Elucidate the mechanisms and pathways of lupus skin involvement and factors leading to skin damage.
  • Investigate organ-specific differences in RNA expression and the possible effects of those differences on disease and end-organ damage.

Chapter 3: New Treatments and Interventions

The goals of treatments for lupus typically have focused on decreasing inflammation and pain while preventing tissue damage and complications. However, no effective targeted therapies exist for the most severe manifestations of the disease (e.g., lupus nephritis, cardiac involvement, and neuropsychiatric lupus). Many of the existing medications have serious side effects, and no medications have been approved for the treatment of lupus in children. In 2011, the FDA approved Benlysta® (belimumab) for the treatment of lupus in adults, making it the first drug in 56 years to be approved for the condition. Despite this significant milestone, developing new drugs for lupus remains challenging. Some of the most important work in lupus in the coming years will focus on improving the ability to diagnose and treat the disease and its complications. Improvements in these areas will depend largely on further developments in four key areas: preclinical and translational research, the identification and validation of biomarkers and surrogate endpoints for use in clinical trials, therapeutic development activities, and well-designed interventional studies.

In the past few years, several advances related to the development of new therapies have occurred. New efforts have begun to explore the value of "repurposing" drugs approved for other conditions to treat lupus. Progress has been made on identifying new biomarkers (e.g., interferon-alpha signature) and exploring potential new therapeutics, including epigenetic modulators, and agents that target the type I interferon pathway. Researchers also are increasingly incorporating into clinical trials measures of outcomes that are most important to patients, such as improved symptom and quality of life assessments, increased tolerability of drug regimens, and more effective management of co-morbid conditions. There also is interest in increasing the number of studies that compare the effectiveness of various interventions.

Research Objectives

Broad areas of potential research directions include:

Biomarker Development and Validation

  • Characterize longitudinal samples to identify molecular signals or other biomarker signatures that could be predictors of a flare.
  • Develop and validate biomarkers for specific outcomes (e.g., end-stage renal disease, cardiovascular disease).
  • Relate various biomarkers to clinical subtypes, disease activity, and genetic predisposition to improve disease stratification.
  • Advance proteomics and integrate with other –omics approaches to identify novel biomarkers.
  • Analyze biomarker and/or pharmacogenomic data from studies in well-defined cohorts to identify predictors of response, as well as toxicity to specific therapies.

Drug Development

  • Develop organ specific therapies, such as for kidney disease.
  • Design early-stage clinical trials to assess candidate therapeutics.
  • Conduct dose finding studies for therapeutics to improve efficacy and decrease side effects.
  • Develop methods for targeted delivery of drugs to the immune system, tissue resident cells, or organs (e.g., monoclonal antibody-toxin conjugates to target and directly kill specific cells).
  • Establish therapeutic target-based drug levels to ensure current and future therapeutics are being titrated effectively in individual patients.
  • Develop new therapeutics, or improved formulations of existing therapeutics, that can be used as more effective long-term treatments for lupus with improved safety compared to therapies currently in clinical use.

Clinical Trials

  • Study and develop new experimental immunotherapies and improve existing immunotherapies.
  • Improve disease management by determining optimal dosing of steroids to maximize effectiveness and minimize toxicity.
  • Design clinical trials to determine whether treat-to-target approaches minimize damage to organs such as the kidney, joints, or brain, and improve patient outcomes.
  • Study novel combinations of existing and emerging therapies guided by mechanism-based models with agents that target these mechanisms.
  • Develop evidence-based criteria for if or when maintenance therapy can be discontinued or whether drug holidays are feasible.
  • Repurpose existing drugs to treat lupus-related disease.
  • Study the comparative effectiveness of existing medications for specific lupus indications.
  • Improve study designs to maintain statistical and clinical rigor in the short-term and generalizability in the long-term.
    • Develop new adaptive or other alternative clinical trial designs.
    • Match endpoints to other key aspects of trial design, such as inclusion/exclusion cutoffs.
    • Include concrete endpoints, biomarkers, and relevant patient-reported outcomes (PROs) for all phases of clinical trials.
    • Incorporate results of basic studies of disease mechanisms into clinical trials.
    • Collect correlative data and specimens in clinical trials to facilitate linking –omics patterns to phenotypes.
    • Conduct long-term follow-up of participants in clinical research to optimize interpretation and generalizability of results.

Patient-Centered Research Opportunities

  • Identify individuals at highest risk of developing lupus and develop targeted preventive interventions for those groups.
  • Improve assessment of pain, fatigue, physical function, and other symptoms by employing validated PROs (e.g., PROMIS®—the Patient Reported Outcomes Measurement Information System®) in lupus; understand how outcomes change over time, how they are affected by interventions and treatment, and how lupus patients compare to patients with other diseases.
  • Clinically validate adult and pediatric PROs as response criteria for clinical trials.
  • Investigate the effects of sociodemographic differences in patient populations on clinical responses to different medications.
  • Develop approaches to enable precision medicine in lupus.
  • Identify social determinants of health among patients with lupus.
  • Bring patients in as “field researchers” to contribute data through social media and biometric devices to facilitate patient-centered approaches to autoimmune disease research.

Chapter 4: Diagnosis and Clinical Care

As with any disease, early diagnosis of lupus often leads to the most successful treatment. In its early stages, lupus can resemble a number of diseases, many of which require different courses of treatment. Moreover, the disease manifestations can develop at different times and often are not all present at once. Therefore, the accumulation of enough signs and symptoms to fulfill the diagnostic criteria for lupus takes time. The lack of a specific diagnostic test for lupus results not only in delayed diagnosis and treatment, but also more severe disease manifestations, and worse patient outcomes.

Treating lupus can be difficult, as well. The features of lupus vary widely among individuals, as do optimal treatment plans, which are tailored to the individual’s needs and may change over time. Some goals of treatment are to prevent flares, to treat them when they do occur, and to minimize organ damage and complications. In light of the potentially harmful side effects of many of the existing therapies (e.g., corticosteroids), researchers are working to develop ways to limit or offset the use of such medications. Researchers also are looking for ways to improve diagnosis and clinical care through the use of biomarkers and new approaches for clinical monitoring and treatment.

Research Objectives

Broad areas of potential research directions include:

Biomarkers Usage in Clinical Practice

  • Clinically validate existing biomarkers and develop and validate new biomarkers for pediatric and adult cohorts.
  • Standardize methods for assessing and reporting biomarkers and PROs.
  • Investigate risk factors and biomarkers associated with a variety of outcomes to enable more effective, earlier intervention.
  • Utilize both existing and emerging biomarkers with acceptable sensitivity and specificity to personalize treatment for individual patients.
  • Develop methods to improve the information obtained from tissue biopsies (e.g., genetic makeup and molecular profile) so that it can be used to guide the choice of therapeutics or stratification into an appropriate clinical trial.
  • Identify biomarkers of steroid response to ensure adequate dosing.
  • Develop companion biomarkers for available therapies to identify responders early.

Clinical Monitoring and Treatment

  • Incorporate new imaging technologies into patient care.
  • Clinically validate existing lupus quality indicators and develop new quality measures to address important gaps.
  • Develop organ-specific surrogate outcomes measures.
  • Develop steroid-sparing treatments or other treatment regimens to decrease long-term damage by toxic therapies.
  • Develop evidence-based standards for steroid use for lupus treatment.
  • Investigate the basis of the major disease subsets of lupus, such as glomerulonephritis, cutaneous lupus, autoimmune hemolytic anemia, anti-phospholipid syndrome, neonatal lupus, and others.
  • Develop non-invasive tests to predict and monitor lupus activity.
  • Develop simpler ways to assess lupus disease activity (e.g., PRO-wearable devices, downloadable apps).
  • Encourage patients to contribute PRO data through social media and biometric devices to facilitate personalized medicine approaches to autoimmune diseases; include a focus on children due to their ongoing development to gain an understanding of the effect of lupus on children’s health-related quality of life.
  • Use PROs to monitor treatment response and assess the efficacy and safety of interventions.
  • Investigate differential treatment responses that are affected by race, sex, age, and ethnicity, as well as their influence on differential organ involvement.
  • Increase ethnicity-specific risk assessment and monitoring.
  • Investigate factors affecting long-term outcomes in lupus (e.g., renal failure, cardiovascular disease, osteoporosis) in order to define preventive strategies to improve outcomes.

Chapter 5: Behavioral, Biopsychosocial and Health Services Research

While research continues to elucidate the biological underpinnings of lupus occurrence and treatment, it is imperative to continue to improve the patient experience. Behavioral and social science research constitute an important component of treating the whole individual, not just the disease. The use of PROs is critical to capturing the patient’s voice and understanding the impact of lupus on an individual’s functioning and quality of life. The NIH Common Fund’s PROMIS® initiative has aided the development and validation of robust PRO tools to gather information on many health-related concerns, such as pain, fatigue, depression, and physical functioning. PROMIS tools can be utilized to measure changes over time in response to treatment and can be integrated into clinical trials, point-of-care visits, and large-scale surveys.

In addition, outcomes for patients have been associated with the health care systems in which they participate. The ability of lupus patients to access subspecialty providers can have a significant impact on disease progression and complications. Socioeconomic status, location, and insurance status are key components of health services delivery, and have been correlated with outcomes for lupus patients. The widespread adoption of electronic health records provides novel data sources for future exploration of these factors.

Research Objectives

Broad areas of potential research directions include:

Behavioral Research

  • Determine the effect of lupus-related cognitive impairment on disease outcomes; test existing instruments (e.g., the NIH Toolbox) or develop new tools to assess and mitigate the impairment.
  • Understand the relationship between patient preferences and outcomes, and identify methodologies to improve treatment adherence and patient-provider interactions.
  • Define how genetic and epigenetic factors influenced by the environment impact neuro-cognitive function and illness-related behaviors.
  • Examine the effects of exercise, stress, sleep, and fatigue on disease processes (e.g., presentation, symptom flares) and patient functioning (e.g., depression).
  • Develop behavioral interventions to assist patients in managing their disease.
  • Integrate new technologies, such as mobile-health technologies (e.g., smart phone apps), to enhance research on the role of behavioral factors in lupus disease outcomes.

Biopsychosocial Research

  • Develop new, or apply existing methodologies to assess cognitive functioning in lupus patients, and determine the impact of cognitive abilities on disease management and progression.
  • Develop, validate, and implement outcome assessment tools (e.g., PROMIS® measures) as endpoints for lupus clinical trials.
  • Develop and validate biopsychosocial strategies and interventions for the management of lupus to assist patients in coping with their disease.
  • Identify, test, and provide interventions that encourage healthy behaviors at the community level.

Health Services Research

  • Develop models to improve local access to culturally sensitive care.
  • Develop and implement strategies to improve communication between physicians and patients.
  • Develop measures of patient engagement with health care providers and insurers.
  • Leverage emerging data infrastructure tools (e.g., electronic health records, mobile technologies) to standardize and improve the quality and safety of healthcare delivered to individuals with lupus.
  • Use large, systematic population samples that include detailed geographical data, health records, and PROs to identify new factors contributing to observed disparities in individuals with lupus.
  • Examine the effects of socioeconomic status and ethnicity on access to care, and assess their contribution to aggregate disease burden.
  • Develop strategies to improve coordination of care between primary care physicians and specialists, especially for economically disadvantaged patients where care is likely to be fragmented.
  • Understand nationwide variation in lupus care and treatment; identify and test interventions to enhance or standardize care to improve patient outcomes.

Chapter 6: Special Populations

As already stated, lupus is a heterogeneous disease with complex and variable manifestations. Epidemiological studies have identified significant sex, racial, and ethnic disparities in outcomes for lupus patients. Although some lupus manifestations (e.g., lupus nephritis) are not sex-specific, the biological basis of the female predisposition in lupus susceptibility requires further exploration. While the sex disparity is commonly attributed to hormonal effects, other mechanisms, such as defective tolerance and inefficient apoptosis of autoreactive cells, have also been implicated. Detailed and definitive explanations are still needed, and additional research is being pursued.

In addition, racial and ethnic disparities in lupus present interesting challenges for researchers to explore. Compared to Whites, African Americans show a 3-to-5-fold higher prevalence of lupus, and have more severe clinical manifestations and organ damage from the condition, especially to the kidneys. In addition, long-term longitudinal outcome studies, such as the Lupus in Minorities: Nature vs. Nurture (LUMINA) multiethnic cohort, have shown that disease manifestations are as serious in Hispanics as in African Americans.

Lupus often strikes women in their early working and childbearing years, and it can interfere with a woman’s ability to work, raise a family, or, in some cases, even care for themselves. Women with inactive disease who become pregnant generally experience excellent outcomes. However, during active disease, complications are common. In recent years, researchers have identified clinical signals and biomarkers that can indicate poor pregnancy outcomes, allowing earlier interventions. Researchers are now beginning to explore long-term developmental outcomes of children born to women with lupus.

Finally, while rare, childhood-onset lupus patients often experience more severe disease manifestations and higher disease burden as they live longer with the disease. The epidemiology of lupus in children is poorly understood. Further, the effect of the disease on the development and maturation that occurs during childhood and adolescence has not been well-delineated. This is especially true for disease assessment and treatment. Additionally, little is known about the special needs of children with lupus with respect to social and emotional well-being.

In 2001, the scientific community formed the Childhood Arthritis and Rheumatology Research Alliance (CARRA), an organization of pediatric rheumatologists committed to advancing the health and quality of life of children with rheumatic diseases and arthritis. Researchers within the CARRA seek to answer critical research questions to elucidate the causes of rheumatic diseases in children, determine the best treatments, and track long-term outcomes. The CARRAnet registry was established with support from the American Recovery and Reinvestment Act as part of CARRA to create a unified, scalable informatics infrastructure and to engage families, patients, and communities in addressing critical clinical research questions. A number of clinical trials leverage the CARRA infrastructure. For example, the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) study, which tested the use of statins to prevent atherosclerosis in pediatric lupus patients, was conducted as part of the CARRA.

Research Objectives

Broad areas of potential research directions include:

Health Disparities

  • Investigate the various genetic, cognitive, environmental, sociological, and healthcare system factors observed in lupus health disparities, and how these interact and contribute to disparities in incidence/prevalence, age of onset, severity, rate of progression, and long-term outcomes.
  • Develop strategies and interventions to eliminate disparate outcomes and reduce disease in affected populations.
  • Develop culturally competent clinical practice and treatment guidelines.
  • Support research on the role of modifiable risk factors in contributing to disparities in lupus morbidity and mortality (e.g., poverty, employment, stress, access to providers).

Lupus and Pregnancy

  • Define and evaluate clinical biomarkers to predict adverse pregnancy outcomes in women with lupus, and develop clinical monitoring plans to effectively manage risks during pregnancy.
  • Study long-term outcomes in children of mothers with lupus to provide science-based information on pregnancy and breastfeeding.

Childhood-Onset Lupus

  • Identify best practices for multidisciplinary approaches to treatment and transitioning from pediatric/adolescent care to adult care.
  • Determine if and how childhood-onset lupus (particularly onset before puberty) is distinct from adult-onset lupus.
  • Define clinical parameters to determine when research studies should be performed separately in pediatric and adult cohorts, and when joint protocols with both children and adults with lupus are appropriate.
  • Determine clinical targets (e.g., blood pressure, lipid levels) for children with lupus that indicate optimal disease management and better long-term outcomes.

Lupus Across the Lifespan

  • Investigate lupus in elderly populations.
  • Determine the long-term effects of lupus in terms of organ damage, physical function, and comorbidities.

Chapter 7: Training and Collaborations

The future of lupus research will rely on a well-trained workforce, as well as robust collaborations between federal, non-profit, and private organizations. As noted earlier, the NIAMS leads the LFWG, which provides a forum for representatives from all relevant stakeholders to share information and coordinate lupus-related activities.

Currently, several federally supported population-based lupus registries are serving to generate better prevalence and incidence estimates for lupus. In addition, lupus biospecimen repositories, such as the Lupus Family Registry and Repository supported by the NIAMS, are available to the research community.

Many novel partnerships have been developed in recent years. For example, the NIH Accelerating Medicines Partnership (AMP) Rheumatoid Arthritis (RA)/Lupus Network was launched in February 2014, as part of a public-private partnership between the NIH, FDA, ten biopharmaceutical companies, and multiple non-profit organizations. The AMP RA/Lupus Network is a unique program designed to accelerate discoveries and to improve patient care as rapidly as possible. In addition, in 2015, through a grant from the CDC, an initiative to create a National Public Health Agenda for Lupus was launched to address strategies for promoting and prioritizing a public health approach to lupus. The effort will provide a blueprint for all stakeholders to guide action surrounding future policy, planning and advocacy initiatives across four domains: epidemiology and surveillance, environmental strategies, health system strategies, and community-clinical linkages.

Research Objectives

Broad areas of potential research directions include:

  • Enhance primary care physician and pediatric resident training programs to improve diagnosis and management of lupus.
  • Develop training programs for researchers to obtain outstanding clinical research and animal model expertise, ensuring robust experiences in experimental design to improve the rigor and reproducibility of research results.
  • Facilitate cross-disciplinary research through training opportunities in bioinformatics, systems biology, imaging, brain biology, and other disciplines with potential for advances in lupus research and patient care.
  • Develop a growing cadre of young investigators with experience using large-scale databases, including but not limited to Medicare and Medicaid systems and private insurers, to conduct epidemiological and health services research.
  • Promote lupus research opportunities among the scientific community in order to attract the best and brightest researchers to the lupus field.

  • Integrate pediatric subspecialties into existing and new partnerships, networks, and registries.
  • Increase interdisciplinary collaborations between clinicians and basic scientists in areas such as molecular biology and structural biology.
  • Expand partnerships between pharmaceutical companies and federal, academic, and non-profit organizations to enable access to licensed products for conducting pre-clinical studies in animal models, or for development of new products for adults and children aimed at genetically-based drug targets.
  • Identify impediments and develop evidence-based solutions to enhance lupus patient participation in clinical trials and studies, particularly among. minorities
  • Engage and incorporate patient advocates in clinical trial networks as liaisons between researchers and patients to improve clinical trial recruitment.

The lupus community has many avenues available to improve the health and well-being of individuals affected by lupus. The potential research directions presented here have been informed by significant consultation with the research community, patient advocacy groups, and the general public. However, it is not an exhaustive list. This Action Plan for Lupus Research will help to inform priority-setting processes among all lupus-related organizations. It is intended to serve as a guide for investigators as they develop independent approaches to address the numerous scientific opportunities in lupus. Basic, translational, and clinical research discoveries and emerging technologies will present additional opportunities to advance our understanding of lupus and how best to manage and ultimately prevent and cure the condition. The NIH and stakeholders in the academic, non-profit, and private sector will continue to work to support the best science and advance lupus research with the resources available.

Appendix 1: Overview of the Development Process

The structure of the FY 2015 NIH Action Plan for Lupus Research is similar to that of the 2007 report on the Future Directions of Lupus Research, with chapters focusing on etiology, disease mechanisms, development of new treatments, diagnosis and clinical care, special populations, and health services research. In addition, new chapters have been added focusing on behavioral and biopsychosocial research, and research training and collaborations. The NIAMS Long-Range Plan for FY 2015-2019 serves as companion piece to the new Action Plan since many of the needs and opportunities presented in that document are highly relevant to lupus research. The NIAMS will continue to partner with other NIH Institutes, Centers, and Offices, health advocacy and professional organizations, and industry to advance lupus research.

In December 2014, the NIAMS began developing the plan by gathering input from the NIH components that invest in lupus research. Several NIH Institutes, Centers, and Offices provided information on ongoing programs, research advances, and future research directions. To obtain public input on topics to include, the NIAMS also issued a Request for Information (RFI) in December 2014 (Appendix 2). The RFI was posted on the NIAMS website and in the NIH Guide for Grants and Contracts, and it encouraged feedback from researchers, professional and patient advocacy organizations, health care providers, and patients and their families. The comment period spanned 59 days. Respondents were asked to provide input on the most significant advances and publications since 2007, the most important scientific opportunities in lupus research, areas that are ready for progress in the short term, gaps to be addressed in order to advance lupus research, and topics to add or remove from the Broad Goals and Priorities elaborated in the 2007 plan. General comments were also encouraged. NIAMS received 36 responses through the RFI.

The Institute then prepared a draft Action Plan that incorporated the information gathered from the NIH components and the RFI. To obtain focused input on the draft plan, the NIAMS held a webinar with lupus researchers and lupus-related organizations on May 27, 2015 (Appendix 3). The webinar included approximately 60 individuals, comprising lupus researchers with broad expertise, scientific and lay representatives from lupus-related organizations, and programmatic and subject matter experts from several NIH ICs. Participants were encouraged to gather and share the views of the broader research community by consulting a diverse set of colleagues in advance of the webinar. Updates on the progress of the planning process were provided at the February 2015, June 2015, and September 2015 NIAMS Advisory Council meetings, and at the October 2014, April 2015, and October 2015 Lupus Federal Working Group meetings. Copies of the slides prepared for those updates were shared with the staff to the Congressional Lupus Caucus.

In July 2015, the draft Action Plan was posted on the NIAMS website for 51 days, and comments were gathered via an RFI published in the NIH Guide for Grants and Contracts (Appendix 2). Respondents were asked to provide feedback on the draft plan. NIAMS received 10 responses through the RFI. All comments were reviewed carefully by Institute staff and incorporated into the document, as appropriate. The final Action Plan was provided to the Congressional Lupus Caucus, posted on the NIAMS website, and widely disseminated to the community.

Appendix 2: Requests for Information Published in the NIH Guide For Grants and Contracts

Request for Information (RFI) on the Future Directions of Lupus Research Notice Number: NOT-AR-15-007.

Request for Information (RFI) on the Action Plan for Lupus Research Notice Number: NOT-AR-15-018.

Appendix 3: Webinar Participants

The Future Directions of Lupus Research

May 27, 2015, 1:00-4:00 P.M.

ARNTSEN, Kathleen A.
Lupus and Allied Diseases Association, Inc.

BRIDGES, S. Louis, Jr., M.D., Ph.D.
University of Alabama Medicine
Representing the American College of Rheumatology

BRUNNER, Hermine I., M.D., M.Sc., M.B.A.
Cincinnati Children’s Hospital Medical Center

CANTOR, Kimberly
Lupus Foundation of America

CHONG, Benjamin, M.D.
University of Texas Southwestern Medical Center

CLARK, Marcus, M.D.
University of Chicago Medical Center

COLLINS, Mary, Ph.D.
Brigham and Women's Hospital Harvard
Representing the S.L.E. Lupus Foundation | Lupus Research Institute

Brigham and Women's Hospital

CRAFT, Joseph, M.D.
Yale School of Medicine

CROW, Mary K., M.D.
Hospital for Special Surgery Weill Cornell Medical College
Representing the Alliance for Lupus Research

DIAMOND, Betty, M.D.
The Feinstein Institute for Medical Research
Representing the Lupus and Allied Diseases Association, Inc.

ELKON, Keith, M.D.
University of Washington

GAFFNEY, Patrick M., M.D.
Oklahoma Medical Research Foundation

Medical University of South Carolina

GROSS, Diane, M.P.H.
S.L.E. Lupus Foundation | Lupus Research Institute

HOLERS, V. Michael, M.D.
University of Colorado Denver

KAMEN, Diane L., M.D., M.S.
Medical University of South Carolina
Representing the Lupus Foundation of America

MCMAHON, Maureen A., M.D.
University of California, Los Angeles School of Medicine

NIEWOLD, Timothy B., M.D.
Mayo Clinic, Rochester
Representing the Rheumatology Research Foundation

PASCUAL, M. Virginia, M.D.
Baylor Institute for Immunology Research

Northwestern University Feinberg School of Medicine

RICHARDSON, Bruce C., M.D., Ph.D.
University of Michigan

ROVIN, Brad H., M.D.
Ohio State University
Representing the American Society for Nephrology

University of Michigan
Representing the Lupus Foundation of America

SIFFEL, Csaba, M.D., Ph.D.
Arthritis Foundation

Texas Children's Hospital & Baylor College of Medicine
Representing the American Society of Pediatric Nephrology

WERTH, Victoria, M.D.
Hospital of the University of Pennsylvania & the Veteran's Administration Medical Center
Representing the Society for Investigative Dermatology

WILLIAMS, Edith M., Ph.D., M.S.
University of South Carolina

WOFSY, David, M.D.
University of California, San Francisco School of Medicine

YELIN, Edward H., Ph.D.
University of California, San Francisco School of Medicine

American College of Rheumatology

ABBOT, Kevin, M.D., M.P.H.
National Institute of Diabetes and Digestive and Kidney Diseases

BEGG, Lisa, Dr.PH, R.N.
Office of Research on Women's Health

BOLLAND, Silvia, Ph.D.
National Institute of Allergy and Infectious Diseases

BUSCHMAN, Justine, M.S.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

BURROWS, Stephanie Y., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

CARTER, Robert H., M.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

CHANDLER, Kelly J., Ph.D.
National Institute of Environmental Health Sciences

CIBOTTI, Ricardo, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

FLESSNER, Michael, M.D., Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Environmental Health Sciences

GOLDMUNTZ, Ellen, M.D., Ph.D.
National Institute of Allergy and Infectious Diseases

HOWCROFT, Kevin, Ph.D.
National Cancer Institute

HUMBLE, Michael, Ph.D.
National Institute of Environmental Health Sciences

JOHNSON, David, Ph.D.
National Institute of Allergy and Infectious Diseases

KAPLAN, Mariana, M.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

KATZ, Stephen I., M.D., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

KESTER, Mary Beth, M.S.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

KIRBY, Ruth, R.N.
National Heart, Lung, and Blood Institute

LINDE, Anita M., M.P.P.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Institute of Allergy and Infectious Diseases

LOWDEN, Mia, Ph.D.
National Institute of Allergy and Infectious Diseases

MANCINI, Marie, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

MARRON, Kathryn, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

MELILLO, Amanda, Ph.D.
National Institute of Dental and Craniofacial Research

REUSS, Andreé (Reaya) E., M.S.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

SARKAR, Rita, Ph.D.
National Heart, Lung, and Blood Institute

National Institute of Environmental Health Sciences

SILVER, Cheryl
National Institute of Allergy and Infectious Diseases

National Institute of Arthritis and Musculoskeletal and Skin Diseases

TONKINS, Wm. Phil, Jr., Dr.PH, M.S.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

WANG, Yan, M.D., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

WARREN, Ronald, Ph.D.
National Heart, Lung, and Blood Institute

WITTER, James, M.D., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases

Appendix 4: Staff Acknowledgements

The following NIAMS Staff from the Division of Skin and Rheumatic Diseases and the Office of Science Policy, Planning and Communications contributed to the development of this report.

Stephanie Y. Burrows, Ph.D.
Mary Beth Kester, M.S.
Anita M. Linde, M.P.P.
Marie Mancini, Ph.D.
Kathryn Marron, Ph.D.
Andreé E. Reuss, M.S.
Susana A. Serrate-Sztein, M.D.
Wm. Phil Tonkins Jr., Dr.PH, M.S.
Yan Wang, M.D., Ph.D.
James Witter, M.D., Ph.D.

Last Updated: July 2020


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Typically materials that are more than 5 years old will be archived

Polymyalgia Rheumatica

What is polymyalgia rheumatica? Polymyalgia rheumatica causes muscle pain and stiffness in the neck, shoulder, and hip. The pain and stiffness usually occur in the morning or when you haven’t been moving for a while. It typically lasts longer than 30 minutes. For most people, the condition develops over time. But for some people it can start quickly – even overnight. In addition to stiffness, you may have a fever, weakness, and weight loss. Polymyalgia rheumatica usually goes away within one year, but it could last several years. People with polymyalgia rheumatica often have giant cell arteritis a disorder associated

What is osteonecrosis? Osteonecrosis is a bone disease. It results from the loss of blood supply to the bone. Without blood, the bone tissue dies. This causes the bone to collapse. It may also cause the joints that surround the bone to collapse. If you have osteonecrosis, you may have pain or be limited in your physical activity. Osteonecrosis can develop in any bone, most often in the: Thigh bone (femur). Upper arm bone (humerus). Knees. Shoulders. Ankles. It is also called: Avascular necrosis. Aseptic necrosis. Ischemic necrosis.

What is vitiligo? Vitiligo is a chronic (long-lasting) disorder that causes areas of skin to lose color. When skin cells that make color are attacked and destroyed, the skin turns a milky-white color. No one knows what causes vitiligo, but it may be an autoimmune disease. In people with autoimmune diseases, the immune cells attack the body’s own healthy tissues by mistake, instead of viruses or bacteria. A person with vitiligo sometimes may have family members who also have the disease. There is no cure for vitiligo, but treatment may help skin tone appear more even.

Knee Problems

What are knee problems? Knee problems happen when you injure or develop disease in your knee and it can’t do its job. The knees provide stable support for the body. They also allow your legs to bend and straighten. Both flexibility and stability are needed to stand, walk, run, crouch, jump, and turn. Other parts of your body help the knees do their job. These are: Bones. Cartilage. Muscles. Ligaments. Tendons.

Sports Injuries in Youth: A Guide for Parents

What are sports injuries in youth? Although sports injuries can range from scrapes and bruises to serious brain and spinal cord injuries, most fall somewhere between the two extremes. Here are some of the more common types of injuries: Muscle sprains and strains. Injuries of a growth plate, area of tissue at the end of the long bones in growing children and teens. Injuries from overuse of muscles and tendons. Learn more about sports injuries.

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text:
3256 RIVER ROAD Ottawa, ON
$ 599,000
Property Attributes
  • MLS#1210868
  • TypeLand
  • CityOttawa
  • NeighbourhoodOsgoode
  • Postal CodeK4M 1B4
  • Style
  • Price$ 599,000
  • Bedrooms0
  • Full Bathrooms0
  • Half Bathrooms0
Listing Provided Courtesy Of:
Power Marketing Real Estate Inc.
Property Description

Great opportunity! Approx. 4000 SQFT bldg. on a 2 Acre lot includes an active restaurant & 2 BDRM apartment (rented @ 800/month), beside boat launch to the river & skido trails for winter, many uses allowed for this great building. Building, business and all equipment is included in the asking price. Owner is retiring, close to Manotick & Osgoode Village right on busy River Rd! No financial statements given before a conditional accepted offer received. Net operating and gross income is projected.Present owner runs the business too. The property sold including the business without providing any statements. (id:27)

Price History
9/17/2020 Listed $599,000

General Features

Garage no
Listing Type Vacant Land
Neighbourhood Osgoode
Parking no
Property Type Vacant Land
Terms SALE
Wheel Chair Access no
Zoning RR7

Interior Features

Fireplace no

Exterior Features

Lot Frontage 310.0
Pool Y/N no

  • Foreclosure
  • Views
  • Short Sale
  • New Construction
  • Adult
  • Lease To Own
  • No Strata Fees
  • Furnished
  • Master On Main
  • Air Conditioning
  • Seller Finance
  • Green
  • Fixer Upper
  • Horse
  • Golf
  • Fireplace
  • Deck
  • Garage
  • Basement
  • Pool

Property vs Postal Code Average in K4M 1B4

AVG $1.03M
AVG 12

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text:
Water Views
Lot 9 John Wilson Pl Ladysmith, BC
$ 225,000
Property Attributes
  • MLS#832686
  • TypeLand
  • CityLadysmith
  • AreaLadysmith - Town of
  • Postal Code
  • Style
  • Price$ 225,000
  • Bedrooms0
  • Full Bathrooms0
  • Half Bathrooms0
  • Lot Size5,370 SqFt
Listing Provided Courtesy Of:
Century 21 Harbour Realty Ltd.
Property Description

Ocean Views & Spectacular Vistas! Phase 4 in Holland Creek Estates is now offering 20 fully engineered building lots with under ground services to the property line w some lots accommodating suites. Holland Creek Estates is a development w a focus on maintaining & accentuating the natural beauty of the area. With a focus on preserving the natural integrity, 42% of this project lands has been set aside for natural parkland, trails & creeks. Within a few steps you will find a multitude of trail systems including the Holland Creek Trail or for the more adventurous Heart Lake. Within close proximity to the local amenities that the charming Town of Ladysmith has to offer including Transfer Beach, Sports Plex & one can't forget the famous Cinnamon Buns' at the Old Town Bakery. Ladysmith gives you fast access to the Nanaimo Airport and BC Ferries and their connections to the world.All information should be verified if fundamental to purchase. Disclosure Statement available upon request.

Price History
7/29/2020 Listed $225,000

General Features

Garage no
Listing Type Vacant Land
Parking no
Terms SALE
Wheel Chair Access no
Zoning R-1-HCA

Interior Features

Fireplace no

Exterior Features

Lot Features Near Golf Course, Sidewalk, Central Location, Easy Access, Family-Oriented Neighbourhood, Marina Nearby, Quiet Area, Recreation Nearby, Shopping Nearby
Lot Frontage 5370
Lot Size 5370
Pool Y/N no

  • Foreclosure
  • Views
  • Short Sale
  • New Construction
  • Adult
  • Lease To Own
  • No Strata Fees
  • Furnished
  • Master On Main
  • Air Conditioning
  • Seller Finance
  • Green
  • Fixer Upper
  • Horse
  • Golf
  • Fireplace
  • Deck
  • Garage
  • Basement
  • Pool

Property vs Postal Code Average in

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This year we are partnering with The Shoe That Grows. We would like to provide 200 children in the community of Pisto, Haiti with a pair of these shoes. The reality is that children grow and so do their feet. These shoes are intended to grow with the child's foot. The shoe is adjustable in three main places and can grow in five sizes.They are made from durable leather, compressed rubber and are made to last for five years. These shoes allow a child to always have a shoe that fits. They are meant to protect their feet from contaminated soil and diseases. Each shoe costs about $15.00. Will you help us reach our goal of 200 pairs of shoes for HAPPY feet?

© 2010 New Jersey for Haiti 501(c)(3)

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Your guide to the New Jersey election 2020

Here's our resource guide for everything you need to know about voting by mail in the 2020 election including New Jersey mail-in ballots, drop box locations and more.

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Register to Vote

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The USA TODAY Network is working to make sure Americans across the country have the resources they need to make their vote count. Click the link below to check your registration and more.

Register to vote

Key Dates to Remember

Dates to remember if you plan to vote in NJ

There are a few key dates New Jersey voters should be aware of including Nov. 3 (deadline for post office receipt of mail-in ballots) and Nov. 10 (deadline for mailed ballots to be received with a postmark).

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We've created a handy video to walk you through what you will find inside the mail-in ballot and how to prepare it for the upcoming election.

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Avoid these mistakes that could get your NJ ballot rejected reviewed election records from the state's May and July elections to find out the most common reasons ballots were rejected. Make sure you follow these rules to avoid those mistakes.

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What does a "mostly by mail" election mean?

Voters in New Jersey will cast their ballots primarily through mail this fall. If you're a registered voter you should get a ballot mailed to you by the second week in October. Voters will receive a vote-by-mail ballot with prepaid return postage. Registered voters who do not receive a ballot should call their county clerk’s office to get one.

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Here's a breakdown of the actual voting process, there are several ways to submit your ballot: The ballots can be deposited in a secure drop box or turned in at a polling place. If the ballot is mailed, it must be postmarked by Nov. 3. Ballots that are mailed must be received with a postmark by 8 p.m. on Nov. 10 to be valid. Ballots that are mailed but without a postmark “due to postal error” by 8 p.m. on Nov. 5 will be valid. This allows for processing time at the post office.

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You can travel to Philadelphia and Camden from many locations in New Jersey. NJ TRANSIT can take you by train or bus to Center City Philadelphia for your commute to work, a family day trip or a special event. Plan your trip for specific schedule and fare information, and get station information including bike and car parking options, and take advantage of great partner discounts on entertainment and admission to destinations in Philadelphia.

Atlantic City Rail Line

Atlantic City Rail Line trains operate between Atlantic City, NJ and Philadelphia 30th Street Station, with connections to River LINE to Camden and Trenton at Pennsauken Transit Center. Lindenwold Station offers convenient connections between PATCO and the Atlantic City Rail Line.

River LINE

River LINE connects communities between Trenton and Camden, just across the river from Philadelphia, for work and play. Enjoy a picturesque ride along the river for festivals and events, unique dining, and historic destinations along the way. Pennsauken Transit Center offers free parking and connections to Atlantic City and Philadelphia via the Atlantic City Rail Line. River LINE is the easiest way to all the attractions along the Camden Waterfront. Relax and ride along the scenic Delaware River, and make the trip part of the fun!

NJ TRANSIT Bus Service & Center City Connector

Express and local bus service connects Philadelphia with many New Jersey locations including: Atlantic City, Bridgeton, Camden, Cherry Hill Mall, Cinnaminson, Delran, Glassboro, Blackwood (Gloucester Premium Outlets), Hammonton (Farley Service Plaza on Atlantic City Expressway), Maple Shade, Merchantville, Moorestown, Mt. Holly, Pennsauken Transit Center (Free Parking), Sicklerville (Avandale Park & Ride - Free Parking), and Willingboro Town Center.

Bus Route 551 provides service between Philadelphia and Atlantic City Bus Terminal, with easy connections to many shore destinations in southern New Jersey, including Ventor, Margate, Longport, Brigantine, Ocean City and Sea Isle City.

The Center City Connector offers service from several New Jersey communities to Center City. The 414 bus connects Maple Shade, Merchantville, and Moorestown with Philadelphia, The 417 bus provides service between Philadelphia and Cinnaminson, Delran, Mt. Holly, Pennsauken, and Willingboro. The 555 bus provides express service to Philadelphia from the Avandale Park & Ride in Sicklerille. Atlantic City Rail Line tickets and weekly/monthly passes are accepted on the 417 bus between Philadelphia and Pennsauken Transit Center.

Bus routes 313/315 provide daily year-round service between Philadelphia, Wildwood, and Cape May. Bus route 316 provides seasonal summer service, and includes a stop at 30th Street Station (at JFK Boulevard) in Philadelphia, allowing easy connections with Amtrak and SEPTA services. In addition, the 316 serves the Gloucester Premium Outlets in Blackwood.

Save 25% or more on round-trip excursion tickets:

  • $20 Atlantic City - Philadelphia (Bus route 551)
  • $30 Wildwood - Philadelphia (Bus route 316)
  • $33 Cape May - Philadelphia (Bus route 316)

Excursion tickets must be purchased at Atlantic City Bus Terminal, Philadelphia Greyhound Bus Terminal, Philadelphia 30th Street Station, Wildwood Terminal, or using the NJ TRANSIT Mobile App, and are valid for 10 days from date of sale.

Plan your trip

Plan your trip for schedules and fare options plus connections with other NJ TRANSIT, SEPTA and PATCO services.

Travel tips

  • The NJ TRANSIT Mobile App offers the most convenient way to purchase your ticket or pass. Use the app to buy and display most tickets or passes on your mobile device.
  • If you are taking the bus, purchase tickets from Ticket Vending Machines (TVMs) at major bus terminals or you may pay the fare on the bus. Most local buses require exact change in coins or $1 bills.
  • Traveling by train? Purchase two one-way tickets for your round-trip transportation prior to boarding the train. A $5 surcharge applies to tickets purchased onboard if you board at a station where ticket vending machines or ticket agents are available.


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      Grand Falls-Windsor, Central/Interior
  • $500.00
    Sat, Oct 17, 9:43 AM
    Holyrood, Avalon Peninsula
    Emerson piano and stool in great condition.
  • $850.00obo
    Tue, Sep 29, 5:36 PM
    carbonear, Avalon Peninsula
    Sherlock-Manning piano for sale. Excellent condition. All strings, hammers and tuning keys in excellent shape. Perfect piano for the beginner. Former music teacher piano.
  • $200.00
    Wed, Oct 28, 3:08 PM
    Torbay, Avalon Peninsula
    Quest plus electric piano with weighted keys and foot pedal.
  • $150.00
    Fri, Sep 11, 8:51 AM
    St. John’s, Avalon Peninsula
    Upright piano. Henry Herbert made by Mason & Risch. Needs tuning and has a few minor chips in keys. Otherwise good working condition. Pick up East end.
  • $60.00
    Sun, Oct 25, 11:28 AM
    Cormack, West Coast
    Casio piano with stand & seat
  • $500.00
    Sun, Sep 20, 10:16 AM
    st johns, Avalon Peninsula
    Piano antique & stool Excellent wood design Keys mostly working 500.00
  • $2,000.00
    Wed, Sep 23, 4:27 PM
    Mount Pearl, Avalon Peninsula
    Upright piano and bench. 13 years old. Like new Ritmuller brand original price 6000.00.
  • $850.00
    Sun, Oct 25, 11:08 AM
    St. John’s, Avalon Peninsula
    Yamaha ( Eterna ) Piano. Model ER- 10 polished Ebony
  • $250.00
    Tue, Oct 27, 1:42 PM
    Witless Bay, Avalon Peninsula
    Casio Piano (CDP-220R) In excellent condition, barley used! Comes with stool and foot pedal.
  • $2,800.00obo
    Tue, Sep 22, 3:02 PM
    St.johns, Avalon Peninsula
    1965 Baby Grand piano( Wurlitzer) in good condition. Asking $ 2800. OBO
  • $1,000.00
    Sun, Oct 18, 12:19 PM
    Bay Roberts, Avalon Peninsula
    Mason & Risch piano, very clean and well taken care of. Stool included. $1000 pick up in Bay Roberts
  • $750.00
    Mon, Sep 21, 7:44 PM
    paradise, Avalon Peninsula
    Mason and Risch Piano in great condition well taken care of reason for selling Daughter lost interest. $750 ono
  • $1,200.00
    Thu, Oct 22, 3:00 PM
    Conception Bay South, Avalon Peninsula
    Yamaha DGX 660 digital piano in perfect condition. Comes with very sturdy stand and 3 pedals. Specs can be found here:
  • $600.00
    Sun, Oct 25, 10:27 AM
    Grand Falls-Windsor, Central/Interior
    Williams upright piano and stool for sale. This beautiful, solid wood piano has served us well and now it's time to find it a new home. Great instrument for beginners and amateurs. Also just a lovely piece of furniture. Reason for selling is kids have moved on to digital piano and we need space. Assistance can be provided for transportation. Feel free to text me on 293-4441
  • $500.00neg
    Tue, Oct 20, 9:23 AM
    Grand Falls-Windsor, Central/Interior
    Antique Piano - Excellent condition. Willis & Co. Age: 114 years Manufactured: 1905 - 1906 Tuned regularly - Works Great
  • $2,500.00obo
    Thu, Oct 15, 9:43 AM
    St. John's, Avalon Peninsula
    Young Chang Console 43" Piano, Polished Ebony. Complete with seat and all music books. Excellent shape.
  • $1,200.00obo
    Fri, Oct 23, 12:51 PM
    Grand falls-windsor, Central/Interior
    Like new and in perfect working order as our kids used it for music lessons for about 5 years each. Music teachers would prefer students practice piano lessons on this instead of a keyboard.
  • $850.00
    Thu, Oct 15, 4:18 PM
    Southern Shore, Avalon Peninsula
    Beautiful piano, only used for about half of a year!! • 4 speakers with volume control and 2 headphone plugins • 130 voices • Metronome • Recording capabilities • 114 Styles Located on the Southern Shore, $850 or next offer!!
  • $700.00
    Thu, Sep 17, 3:38 PM
    C.B.S., Avalon Peninsula
    Kimball upright piano.Piano is from 1950s or 1960s but is in good condition.May need tuning. I'm selling this piano for$700.00 but am open to reasonable offers. If interested please call 709-699-7206. Or 709-834-4231.
  • $2,100.00
    Tue, Oct 27, 6:20 PM
    Bishop's Falls, Central/Interior
    Yamaha P250 Digital Stage Piano is a professional quality stage piano. The P250 has weighted keys with graded action, it also has built in speakers. This keyboard has had some light use and is in excellent condition. Travel bag with wheels makes it easy to get around with keyboard.