Single Disease Process Research Articles

Alexander disease: The story behind an eponym

ABSTRACT In 1949, William Stewart Alexander (1919–2013), a young pathologist from New Zealand working in London, reported the neuropathological findings in a 15-month-old boy who had developed normally until the age of seven months, but thereafter had progressive enlargement of his head and severe developmental delay. The most striking neuropathological abnormality was the presence of numerous Rosenthal fibers in the brain. The distribution of these fibers suggested to Alexander that the primary pathological change involved astrocytes. In the next 15 years, five similar patients were reported, and in 1964 Friede recognized these cases reflected a single disease process and coined the eponym “Alexander’s disease” to describe the disorder. In the 1960s, electron microscopy confirmed that Rosenthal fibers were localized to astrocytes. In 2001, it was shown that Alexander disease is caused by mutations in the gene encoding glial fibrillary acidic protein, the major intermediate filament protein in astrocytes. Although the clinical, imaging, and pathological manifestations of Alexander disease are now well known, few people are familiar with Alexander’s career. Although he did not make a further contribution to the literature on Alexander disease, his observations and accurate interpretation of the neuropathology have justified the continued use of the eponym “Alexander disease.”

Clinical presentation and disease prevalence of captive central bearded dragons (Pogona vitticeps) at veterinary clinics in Australia

Central bearded dragons (Pogona vitticeps) are one of the most popular reptile pets in Australia and around the world. Diseases, including metabolic bone disease, periodontal disease, and gastrointestinal endoparasites commonly affect captive animals. To determine the common reasons these lizards were presented to the veterinarian and to establish the prevalence of disease seen in captive P. vitticeps in Australia, this retrospective study evaluated the clinical records of three exotic pet veterinary hospitals. Records from 724 P. vitticeps were analysed, with 70 reasons for presentation and 88 diseases identified across 1000 visits to the veterinarian. Lethargy was the most reported reason for presentation (n=181). The gastrointestinal tract (18.25%) and skin (18.25%) were the equally most commonly affected organ systems, followed by the musculoskeletal system (15.17%). Endoparasites were the most common single disease process (n=103), followed by metabolic bone disease (n=65), skin wounds (n=59) and periodontal disease (n=48). Of the patients that presented for routine preventive health examinations (n=159), 45.30% received some form of intervention to treat or prevent disease. Many of the conditions that were identified by the veterinarians in this study are traditionally correlated with suboptimal husbandry and may be easily prevented. This study identified the common reasons for presentation to the veterinarian and the prevalence of disease in captive P. vitticeps in Australia, providing the first extensive retrospective analysis of objective reference literature for central bearded dragon owners and aspiring reptile veterinarians.

Proteomic profile of extracellular vesicles in maternal plasma of women with fetal death

Objectives Fetal death is a complication of pregnancy caused by multiple etiologies rather than being the end-result of a single disease process. Many soluble analytes in the maternal circulation, such as hormones and cytokines, have been implicated in its pathophysiology. However, changes in the protein content of extracellular vesicles (EVs), which could provide additional insight into the disease pathways of this obstetrical syndrome, have not been examined. This study aimed to characterize the proteomic profile of EVs in the plasma of pregnant women who experienced fetal death and to evaluate whether such a profile reflected the pathophysiological mechanisms of this obstetrical complication. Moreover, the proteomic results were compared to and integrated with those obtained from the soluble fraction of maternal plasma. Methods This retrospective case-control study included 47 women who experienced fetal death and 94 matched, healthy, pregnant controls. Proteomic analysis of 82 proteins in the EVs and the soluble fractions of maternal plasma samples was conducted by using a bead-based, multiplexed immunoassay platform. Quantile regression analysis and random forest models were implemented to assess differences in the concentration of proteins in the EV and soluble fractions and to evaluate their combined discriminatory power between clinical groups. Hierarchical cluster analysis was applied to identify subgroups of fetal death cases with similar proteomic profiles. A p-value of <.05 was used to infer significance, unless multiple testing was involved, with the false discovery rate controlled at the 10% level (q < 0.1). All statistical analyses were performed by using the R statistical language and environment-and specialized packages. Results Nineteen proteins (placental growth factor, macrophage migration inhibitory factor, endoglin, regulated upon activation normal T cell expressed and presumably secreted (RANTES), interleukin (IL)-6, macrophage inflammatory protein 1-alpha, urokinase plasminogen activator surface receptor, tissue factor pathway inhibitor, IL-8, E-Selectin, vascular endothelial growth factor receptor 2, pentraxin 3, IL-16, galectin-1, monocyte chemotactic protein 1, disintegrin and metalloproteinase domain-containing protein 12, insulin-like growth factor-binding protein 1, matrix metalloproteinase-1(MMP1), and CD163) were found to have different plasma concentrations (of an EV or a soluble fraction) in women with fetal death compared to controls. There was a similar pattern of change for the dysregulated proteins in the EV and soluble fractions and a positive correlation between the log2-fold changes of proteins significant in either the EV or the soluble fraction (ρ = 0.89, p < .001). The combination of EV and soluble fraction proteins resulted in a good discriminatory model (area under the ROC curve, 82%; sensitivity, 57.5% at a 10% false-positive rate). Unsupervised clustering based on the proteins differentially expressed in either the EV or the soluble fraction of patients with fetal death relative to controls revealed three major clusters of patients. Conclusion Pregnant women with fetal death have different concentrations of 19 proteins in the EV and soluble fractions compared to controls, and the direction of changes in concentration was similar between fractions. The combination of EV and soluble protein concentrations revealed three different clusters of fetal death cases with distinct clinical and placental histopathological characteristics.

Multi-modality human phenotyping to examine subjective and objective health afflictions in former professional American-style football players: The In-Person Assessment (IPA) protocol.

BackgroundParticipation in American-style football (ASF), one of the most popular sports worldwide, has been associated with adverse health outcomes. However, prior clinical studies of former ASF players have been limited by reliance on subjective self-reported data, inadequate sample size, or focus on a single disease process in isolation.ObjectiveTo determine the burden of objective multi-system pathology and its relationship with subjective health complaints among former professional ASF players.MethodsThe In-Person Assessment is a case-control, multi-day, deep human phenotyping protocol designed to characterize and quantify pathology among former professional ASF players. Participants, recruited from an on-going large-scale longitudinal cohort study, will include 120 men who report either no health conditions, a single health condition, or multiple health conditions across the key domains of cardiometabolic disease, disordered sleep, chronic pain, and cognitive impairment. Data will be collected from validated questionnaires, structured interviews, physical examinations, multi-modality imaging, and functional assessments over a 3-day study period. A pilot study was conducted to assess feasibility and to obtain participant feedback which was used to shape the final protocol.ResultsThis study provides a comprehensive assessment of objective multi-system pathology and its relationship with subjective health complaints among former professional ASF players.ConclusionThe study will determine whether subjective health complaints among former professional ASF players are explained by objective explanatory pathology and will provide novel opportunities to examine the interrelatedness of co-morbidities. It is anticipated that this protocol will be applicable to other clinical and occupational populations.

JCL Roundtable. Making prevention a priority

Clinical lipidology belongs par excellence to the preventive mode of medical practice. This Roundtable brings two long-time advocates of cardiometabolic prevention and a newly minted preventive cardiologist into a discussion that expands their recent JCL editorial on this topic. Atherosclerosis is a single disease process that leads to approximately 25% of deaths in economically advanced nations and a growing fraction of mortality and morbidity in nations with developing and emerging economies. Our discussants suggest that at least 75% of atherosclerotic cardiovascular disease can be prevented. Diet and lifestyle including physical activity are the cornerstones for this effort. Public and private choices about diet-lifestyle are influenced by economics, education (especially in childhood), inequities, technology, misinformation, and trust. Lipid clinics perform well with pharmacologic treatment of lipid disorders and increasingly give attention to hypertension, obesity, and diabetes as needed. Cardiometabolic prevention in the clinic works best through provider teams. Business considerations and exemplary programs are highlighted.

Engaging Internal Medicine Hospitalists in Antimicrobial Stewardship—a Systematic Review

The purpose of this article is to critically assess the literature on engaging internal medicine hospitalists in antimicrobial stewardship. Few studies exist that describe hospitalist-led antimicrobial stewardship initiatives. Most studies in this review employed quasi-experimental or quality improvement methods. Across the studies included in our analysis, those with interventions that focused on single disease processes (e.g., pneumonia, UTI, SSTI) had a more robust impact on their selected outcomes. In the reviewed literature, engaging internal medicine hospitalists in antimicrobial stewardship efforts resulted in improved antimicrobial appropriateness and decreased broad-spectrum antibiotic usage. Despite being identified as key stakeholders and potential leaders in antimicrobial stewardship efforts, there is a paucity of literature to guide the best incorporation of hospitalists in this work.

Acute Rehabilitation of a 27-Year-Old Man With Failure to Thrive

Background and Purpose: Failure to thrive is a complex medical diagnosis that does not describe a single disease process, but rather a variety of symptoms associated with one or more possible underlying diseases or conditions. It is a diagnosis that is not well-documented outside pediatric or geriatric populations. The purpose of this case report is to present the physical therapy examination and treatment of a 27-year-old Hispanic man with a diagnosis of failure to thrive, a history of superior mesenteric artery syndrome, chronic malnutrition, type 1 diabetes mellitus, and osteopenia. Case Description: A 27-year-old Hispanic man, BMI of 12, admitted to the hospital for acute hypothermia, urinary tract infection, generalized weakness, hypotension, and failure to thrive. The complexity of his medical condition required nearly 2 weeks to stabilize general health prior to initiating physical therapy services. Personal and environmental factors contributed to progressive decline in physical activity prior to this hospital admission and led to increased dependence and support. Outcomes: Blood pressure increased by 18 mm Hg systolic and 20 mm Hg diastolic and stabilized within normal range; 5 repetitions in the 30-second sit-to-stand; functional balance composite score of 35 seconds; 20% reduction in subjective Numeric Pain Rating Scale; supervised bed mobility; maximum assistance stand-pivot transfer; and family to support caregiver needs upon return home. The patient was discharged home with recommendation for continued services through home health care referral. Discussion: Evidence-based literature regarding failure to thrive in the young adult or middle-aged adult population is limited. Therefore, the physical therapy plan of care necessitates the application of interventions shown to be effective in addressing the physical structure and function limitation upon examination generally applied to the geriatric and/or pediatric population. Clinical decision-making focused on improving physical activity and participation are imperative across clinical settings. Manual therapy interventions applied in this case may prove beneficial in the acute care setting to maximize muscle activation within available range of motion elicited through patterns of functional movements emphasizing existing abilities.

Obesity as a Disease, Not a Behavior.

The American Heart Association (AHA) defines ideal cardiovascular health in its 2020 Impact Goals for cardiovascular health promotion and disease prevention to include a body mass index (BMI) <25 kg/m2, which they recognize as an ideal health behavior.1 We urge the AHA as it begins setting its 2030 goals to move beyond the concept of BMI as a health behavior. Equating BMI with behavior confuses the now widely accepted association between BMI and the mechanistically complex disease of obesity.2 In our opinion, it makes little sense to establish goals and metrics that ignore a broad evidence base that supports the view of obesity as a complex, multifactorial disease and expect to achieve meaningful success in managing BMI to promote ideal cardiovascular health. Despite the growing recognition of the complexity of obesity, like cancer decades ago, obesity has been treated as a single disease process with universal prevention and treatment strategies, rather than a fundamentally heterogeneous process with numerous underlying mechanisms and etiologies, each requiring unique prevention and treatment modalities. Obesity and related coronary artery disease, stroke, and other sequelae lead to increased health burden and billions of dollars in healthcare costs in the United States. Examining sources of heterogeneity in the etiology of obesity …

Giant cell arteritis, polymyalgia rheumatica, and late-onset rheumatoid arthritis: Can they be components of a single disease process in elderly patients?

To report two patients with giant cell arteritis (GCA) who developed rheumatoid arthritis (RA) and to review the literature in terms of coexistence of RA, GCA, and polymyalgia rheumatica (PMR). We conducted a comprehensive review of the English literature from 1980 to 2015 to analyze data on the coexistence of GCA and RA. The PubMed, Web of Science, Proquest, and Ovid databases were searched for articles using the term RA combined with temporal arteritis, GCA, and PMR. We identified 17 other cases of coexistent GCA and RA reported in the English literature, together with our 2 cases (19 cases). They included 14 females and 5 males, with a mean age of 74.3 years (range: 57-84) at the time of GCA. The mean age at the time of RA diagnosis was 69.6 years (range 24-83). The average time elapsed between the onset of GCA and the development of RA was 6.7 years (range: 3 month-34 years). RA and GCA were reported as the first disease in 10 cases and 4 cases, respectively. The development of these 2 diseases in a narrow period of time appeared in 4 cases (3 months-19 months). PMR was the first disease in 1 case. RA, GCA, and PMR may appear simultaneously or consecutively; therefore, we suggest that physicians should be alert about such a fact so that a proper diagnosis and treatment could be tailored accordingly.

Patterns of Estimated Glomerular Filtration Rate Decline Leading to End-Stage Renal Disease in Type 1 Diabetes.

The patterns of estimated glomerular filtration rate (eGFR) decline to end-stage renal disease (ESRD) in patients with type 1 diabetes has not been conclusively described. Decline could be linearly progressive to ESRD but with a variable rate. Conversely, decline may be linear but interrupted by periods of plateaus or improvements. This observational study included 364 patients with type 1 diabetes attending the Joslin Clinic who developed ESRD between 1991 and 2013. We retrieved serum creatinine measurements from clinic visits or research examinations up to 24 years (median 6.7 years) preceding the onset of ESRD. Using serial measurements of serum creatinine to estimate renal function (eGFR), we used regression-based spline methods and a data smoothing approach to characterize individual trajectories of eGFR over time for the 257 patients with five or more data points. The rate of eGFR decline per year ranged widely, from -72 to -2 mL/min/1.73 m2 (median -8.5). The trajectories, as characterized with linear regression-based spline models, were linear or nearly so for 87% of patients, accelerating for 6%, and decelerating for 7%. Smoothed trajectories evaluated by a Bayesian approach did not significantly depart from a linear fit in 76%. The decline of eGFR in type 1 diabetes is predominantly linear. Deviations from linearity are small, with little effect on the expected time of ESRD. A single disease process most likely underlies renal decline from its initiation and continues with the same intensity to ESRD. Linearity of renal decline suggests using slope reduction as the measure of effectiveness of interventions to postpone ESRD.

Brainstem Glioma in Adults.

Brainstem gliomas are not nearly as common in adults as they are in children. They are likely the final common consequence not of a single disease process but of several. They can be difficult to diagnose, and are challenging to treat. Clinical studies of this diagnosis are few and generally small. Because of these factors, our understanding of the biology of adult brainstem glioma is incomplete. However, the knowledge base is growing and progress is being made. In this article, we review the current state of knowledge for brainstem glioma in adults and identify key areas for which additional information is required.

Renal diseases in adults with cystic fibrosis: a 40 year single centre experience.

There is a sizable literature describing renal disease in patients with cystic fibrosis. Previous studies have focused on single disease processes alone, most commonly renal stone disease or acute kidney injury. In this study we report for the first time on the prevalence of all forms of renal disease in a cystic fibrosis population. A retrospective review of adult patients with cystic fibrosis attending the Adult Cystic Fibrosis Department at the Royal Brompton Hospital was carried out by searching the department's database to identify patients with renal problems and subsequently retrieving clinical information from medical notes. The prevalence of all renal diseases in our population was 5.1 %. The most commonly identified problem was renal stones. At 2.0 % the prevalence of renal stones in adult patients with cystic fibrosis was comparable to the general population. A range of other renal diseases were identified, the next most common being drug-induced acute kidney injury. A range of cystic fibrosis independent and attributable diseases has been identified but no cystic fibrosis specific disease. In contrast to other cystic fibrosis centres no increased prevalence of renal stones was found.

Network Analysis Reveals Distinct Clinical Syndromes Underlying Acute Mountain Sickness

Acute mountain sickness (AMS) is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS), we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25). These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.

Computer assisted histomorphologic comparision and the expression of AgNORs in the central and peripheral giant cell lesions of the oral cavity and giant cell tumor of the long bone

Objective:Computer-assisted image analysis was attempted to ascertain, if any of the previously described histologic features along with argyrophilic nucleolar organizer regions (AgNORs) could be used to determine the aggressiveness of the central giant cell granuloma of the jaws (CGCG), peripheral giant cell granuloma of the oral cavity (PGCG) and giant cell tumor of the long bones (GCT).Study Design:The study consisted of 20 cases of CGCG, 20 cases of PGCG and 5 cases of GCT. The histological features included were number of giant cells, number of nuclei in each giant cell, number of blood vessels, fractional surface area (FSA) and relative size index (RSI) of giant cells. The histologic parameters were measured using Motic image plus analyzer and AgNORs were evaluated using silver stain.Results:The statistical analysis showed significant differences among various histological parameters between CGCG, PGCG and GCT. A statistically significant difference was noted for the mean number of nuclei, FSA and RSI when GCT was compared with CGCG and PGCG. FSA of histologically aggressive central giant cell granuloma (HA-CGCG) was more compared to histologically non-aggressive central giant cell granuloma (HNA-CGCG). No statistical correlation was observed for AgNORs of multinucleated giant cells and mononuclear cells among CGCG, PGCG and GCT.Conclusion:Based on the present study findings, CGCG and GCT are distinct and separate entities and not a continuum of a single disease process. Histological parameters alone have a little implication on predicting clinical behavior of CGCG. AgNORs alone as a proliferative marker has a limited value in assessing the proliferation potential of giant cell lesions.

Development and Significance of the Frailty Concept in the Elderly: A Possible Modern View

Frailty is an evolving concept that is generally defined in biomedical or psychosocial terms. It is not necessarily related to a specific single disease process. Passing by the theories of Selye (1936) on the exhaustion of the General Adaptation Syndrome,until reaching to the studies of Fried (2001) who, firstly, proposed diagnostic criteria for frailty, in this paper are explored different ways to understand this concept, until endeavour to give a possible modern view. The definition of a frailty syndrome characterized by a multi-system reduction in ?reserve capacity? remains widely accepted.

Comparing clinical predictors of deep venous thrombosis versus pulmonary embolus after severe injury

The traditional paradigm is that deep venous thrombosis (DVT) and pulmonary embolus (PE) are different temporal phases of a single disease process, most often labeled as the composite end point venous thromboembolism (VTE). However, we theorize that after severe blunt injury, DVT and PE may represent independent thrombotic entities rather than different stages of a single pathophysiologic process and therefore exhibit different clinical risk factor profiles. We examined a large, multicenter prospective cohort of severely injured blunt trauma patients to compare clinical risk factors for DVT and PE, including indicators of injury severity, shock, resuscitation parameters, comorbidities, and VTE prophylaxis. Independent risk factors for each outcome were determined by cross-validated logistic regression modeling using advanced exhaustive model search procedures. The study cohort consisted of 1,822 severely injured blunt trauma patients (median Injury Severity Score [ISS], 33; median base deficit, -9.5). Incidence of DVT and PE were 5.1% and 3.9%, respectively. Only 9 (5.7%) of 73 patients with a PE were also diagnosed with DVT. Independent risk factors associated with DVT include prophylaxis initiation within 48 hours (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.36-0.90) and thoracic Abbreviated Injury Scale (AIS) score of 3 or greater (OR, 1.82; 95% CI, 1.12-2.95), while independent risk factors for PE were serum lactate of greater than 5 (OR, 2.33; 95% CI, 1.43-3.79) and male sex (OR, 2.12; 95% CI, 1.17-3.84). Both DVT and PE exhibited differing risk factor profiles from the classic composite end point of VTE. DVT and PE exhibit differing risk factor profiles following severe injury. Clinical risk factors for diagnosis of DVT after severe blunt trauma include the inability to initiate prompt pharmacologic prophylaxis and severe thoracic injury, which may represent overall injury burden. In contrast, risk factors for PE are male sex and physiologic evidence of severe shock. We hypothesize that postinjury DVT and PE may represent a broad spectrum of pathologic thrombotic processes as opposed to the current conventional wisdom of peripheral thrombosis and subsequent embolus.

Comparing clinical predictors of deep venous thrombosis versus pulmonary embolus after severe injury: A new paradigm for posttraumatic venous thromboembolism?

BACKGROUND: The traditional paradigm is that deep venous thrombosis (DVT) and pulmonary embolus (PE) are different temporal phases of a single disease process, most often labeled as the composite end point venous thromboembolism (VTE). However, we theorize that after severe blunt injury, DVT and PE may represent independent thrombotic entities rather than different stages of a single pathophysiologic process and therefore exhibit different clinical risk factor profiles. METHODS: We examined a large, multicenter prospective cohort of severely injured blunt trauma patients to compare clinical risk factors for DVT and PE, including indicators of injury severity, shock, resuscitation parameters, comorbidities, and VTE prophylaxis. Independent risk factors for each outcome were determined by cross-validated logistic regression modeling using advanced exhaustive model search procedures. RESULTS: The study cohort consisted of 1,822 severely injured blunt trauma patients (median Injury Severity Score [ISS], 33; median base deficit, -9.5). Incidence of DVT and PE were 5.1% and 3.9%, respectively. Only 9 (5.7%) of 73 patients with a PE were also diagnosed with DVT. Independent risk factors associated with DVT include prophylaxis initiation within 48 hours (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.36–0.90) and thoracic Abbreviated Injury Scale (AIS) score of 3 or greater (OR, 1.82; 95% CI, 1.12–2.95), while independent risk factors for PE were serum lactate of greater than 5 (OR, 2.33; 95% CI, 1.43–3.79) and male sex (OR, 2.12; 95% CI, 1.17–3.84). Both DVT and PE exhibited differing risk factor profiles from the classic composite end point of VTE. CONCLUSION: DVT and PE exhibit differing risk factor profiles following severe injury. Clinical risk factors for diagnosis of DVT after severe blunt trauma include the inability to initiate prompt pharmacologic prophylaxis and severe thoracic injury, which may represent overall injury burden. In contrast, risk factors for PE are male sex and physiologic evidence of severe shock. We hypothesize that postinjury DVT and PE may represent a broad spectrum of pathologic thrombotic processes as opposed to the current conventional wisdom of peripheral thrombosis and subsequent embolus. LEVEL OF EVIDENCE: Prognostic study, level III.

“Blueberry muffin” rash and large right thigh mass: a unique presentation of Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a clonal proliferation of bone marrow derived antigen-presenting cells that can involve a spectrum of cutaneous findings, with or without internal organ involvement. Neonatal LCH almost always presents with skin findings, usually petechial papules and/or erosions in a seborrheic distribution, with or without extracutaneous involvement. Previously described as varying entities, LCH is now considered a single disease process demonstrating a spectrum of clinical findings. We report a unique case of neonatal LCH presenting with a "blueberry muffin" rash in conjunction with a large soft tissue tumor.

Managing Older Adults With CKD: Individualized Versus Disease-Based Approaches

The last decade has seen the evolution and ongoing refinement of a disease-oriented approach to chronic kidney disease (CKD). Disease-oriented models of care assume a direct causal association between observed signs and symptoms and underlying disease pathophysiologic processes. Treatment plans target underlying disease mechanisms with the goal of improving disease-related outcomes. Because average glomerular filtrate rates tend to decrease with age, CKD becomes increasingly prevalent with advancing age and those who meet criteria for CKD are disproportionately elderly. However, several features of geriatric populations may limit the utility of disease-oriented models of care. In older adults, complex comorbid conditions and geriatric syndromes are common; signs and symptoms often do not reflect a single underlying pathophysiologic process; there can be substantial heterogeneity in life expectancy, functional status, and health priorities; and information about the safety and efficacy of recommended interventions often is lacking. For all these reasons, geriatricians have tended to favor an individualized patient-centered model of care over more traditional disease-based approaches. An individualized approach prioritizes patient preferences and embraces the notion that observed signs and symptoms often do not reflect a single unifying disease process and instead reflect the complex interplay between many different factors. This approach emphasizes modifiable outcomes that matter to the patient. Prognostic information related to these and other outcomes generally is used to shape rather than dictate treatment decisions. We argue that an individualized patient-centered approach to care may have more to offer than a traditional disease-based approach to CKD in many older adults.

Tauopathies: One Disease or Many?

Tauopathies are a group of disorders that have in common abnormal accumulation of tau protein in the brain. Although the different tauopathies have long been considered to be separate diseases, it is now clear that progressive supranuclear palsy, corticobasal degeneration and some forms of tau-positive frontotemporal lobar degeneration share clinical, pathological and genetic features. The important overlap between these disorders suggest they may represent different phenotypes of a single disease process, the clinical result depending on the topography of pathological lesions as well as other unknown factors.