Potential value of electronic health records in capturing data on geriatric frailty for population health.

OBJECTIVES: Despite the availability of many frailty measures to identify older adults at risk, frailty instruments are not routinely used for risk assessment in population health management. Here, we assessed the potential value of electronic health records (EHRs) and administrative claims in providing the necessary data for variables used across various frailty instruments. SETTING AND PARTICIPANTS: The review focused on studies conducted worldwide. Participants included older people aged 50 and older. DESIGN: We identified frailty instruments published between 2011 and 2018. Frailty variables used in each of the frailty instruments were extracted, grouped, and categorized across health determinants and various clinical factors. MEASURES: The availability of the extracted frailty variables across various data sources (e.g., EHRs, administrative claims, and surveys) was evaluated by experts. RESULTS: We identified 135 frailty instruments, which contained 593 unique variables. Clinical determinants of health were the best represented variables across frailty instruments (n = 516; 87 %), unlike social and health services factors (n = 33; ∼5% and n = 32; ∼5%). Most frailty instruments require at least one variable that is not routinely available in EHRs or claims (n = 113; ∼83 %). Only 22 frailty instruments have the potential to completely rely on EHR (structured or free-text data) and/or claims data, and possibly be operationalized on a population-level. CONCLUSIONS AND IMPLICATIONS: Frailty instruments continue to be highly survey-based. More research is therefore needed to develop EHR-based frailty instruments for population health management. This will permit organizations and societies to stratify risk and better allocate resources among different older adult populations.

The Value of Unstructured Electronic Health Record Data in Geriatric Syndrome Case Identification.

OBJECTIVES: To examine the value of unstructured electronic health record (EHR) data (free-text notes) in identifying a set of geriatric syndromes. DESIGN: Retrospective analysis of unstructured EHR notes using a natural language processing (NLP) algorithm. SETTING: Large multispecialty group. PARTICIPANTS: Older adults (N=18,341; average age 75.9, 58.9% female). MEASUREMENTS: We compared the number of geriatric syndrome cases identified using structured claims and structured and unstructured EHR data. We also calculated these rates using a population-level claims database as a reference and identified comparable epidemiological rates in peer-reviewed literature as a benchmark. RESULTS: Using insurance claims data resulted in a geriatric syndrome prevalence ranging from 0.03% for lack of social support to 8.3% for walking difficulty. Using structured EHR data resulted in similar prevalence rates, ranging from 0.03% for malnutrition to 7.85% for walking difficulty. Incorporating unstructured EHR notes, enabled by applying the NLP algorithm, identified considerably higher rates of geriatric syndromes: absence of fecal control (2.1%, 2.3 times as much as structured claims and EHR data combined), decubitus ulcer (1.4%, 1.7 times as much), dementia (6.7%, 1.5 times as much), falls (23.6%, 3.2 times as much), malnutrition (2.5%, 18.0 times as much), lack of social support (29.8%, 455.9 times as much), urinary retention (4.2%, 3.9 times as much), vision impairment (6.2%, 7.4 times as much), weight loss (19.2%, 2.9 as much), and walking difficulty (36.34%, 3.4 as much). The geriatric syndrome rates extracted from structured data were substantially lower than published epidemiological rates, although adding the NLP results considerably closed this gap. CONCLUSION: Claims and structured EHR data give an incomplete picture of burden related to geriatric syndromes. Geriatric syndromes are likely to be missed if unstructured data are not analyzed. Pragmatic NLP algorithms can assist with identifying individuals at high risk of experiencing geriatric syndromes and improving coordination of care for older adults.

Defining and Assessing Geriatric Risk Factors and Associated Health Care Utilization Among Older Adults Using Claims and Electronic Health Records.

BACKGROUND: Using electronic health records (EHRs), in addition to claims, to systematically identify patients with factors associated with adverse outcomes (geriatric risk) among older adults can prove beneficial for population health management and clinical service delivery. OBJECTIVE: To define and compare geriatric risk factors derivable from claims, structured EHRs, and unstructured EHRs, and estimate the relationship between geriatric risk factors and health care utilization. RESEARCH DESIGN: We performed a retrospective cohort study of patients enrolled in a Medicare Advantage plan from 2011 to 2013 using both administrative claims and EHRs. We defined 10 individual geriatric risk factors and a summary geriatric risk index based on diagnosed conditions and pattern matching techniques applied to EHR free text. The prevalence of geriatric risk factors was estimated using claims, structured EHRs, and structured and unstructured EHRs combined. The association of geriatric risk index with any occurrence of hospitalizations, emergency department visits, and nursing home visits were estimated using logistic regression adjusted for demographic and comorbidity covariates. RESULTS: The prevalence of geriatric risk factors increased after adding unstructured EHR data to structured EHRs, compared with those derived from structured EHRs alone and claims alone. On the basis of claims, structured EHRs, and structured and unstructured EHRs combined, 12.9%, 15.0%, and 24.6% of the patients had 1 geriatric risk factor, respectively; 3.9%, 4.2%, and 15.8% had ≥2 geriatric risk factors, respectively. Statistically significant association between geriatric risk index and health care utilization was found independent of demographic and comorbidity covariates. For example, based on claims, estimated odds ratios for having 1 and ≥2 geriatric risk factors in year 1 were 1.49 (P<0.001) and 2.62 (P<0.001) in predicting any occurrence of hospitalizations in year 1, and 1.32 (P<0.001) and 1.34 (P=0.003) in predicting any occurrence of hospitalizations in year 2. CONCLUSIONS: The results demonstrate the feasibility and potential of using EHRs and claims for collecting new types of geriatric risk information that could augment the more commonly collected disease information to identify and move upstream the management of high-risk cases among older patients.

Antibody-Mediated Extreme Insulin Resistance: A Report of Three Cases.

BACKGROUND: Type 2 diabetes mellitus is characterized by relative insulin deficiency and insulin resistance. Features suggesting severe insulin resistance include acanthosis nigricans, hyperandrogenism, weight loss, and recurrent hospital admissions for diabetic ketoacidosis. In rare circumstances, hyperglycemia persists despite administration of massive doses of insulin. In these cases, it is important to consider autoimmune etiologies for insulin resistance, such as type B insulin resistance and insulin antibody-mediated extreme insulin resistance, which carry high morbidity and mortality if untreated. Encouragingly, immunomodulatory regimens have recently been published that induce remission at high rates. METHODS/RESULTS: We describe 3 cases of extreme insulin resistance mediated by anti-insulin receptor autoantibodies or insulin autoantibodies. All cases were effectively treated with an immunomodulatory regimen. CONCLUSION: Although cases of extreme insulin resistance are rare, it is important to be aware of autoimmune causes, recognize suggestive signs and symptoms, and pursue appropriate diagnostic evaluation. Prompt treatment with immunomodulators is key to restoring euglycemia in patients with autoimmune etiologies of insulin resistance.

Comparing clinician descriptions of frailty and geriatric syndromes using electronic health records: a retrospective cohort study.

BACKGROUND: Geriatric syndromes, including frailty, are common in older adults and associated with adverse outcomes. We compared patients described in clinical notes as "frail" to other older adults with respect to geriatric syndrome burden and healthcare utilization. METHODS: We conducted a retrospective cohort study on 18,341 Medicare Advantage enrollees aged 65+ (members of a large nonprofit medical group in Massachusetts), analyzing up to three years of administrative claims and structured and unstructured electronic health record (EHR) data. We determined the presence of ten geriatric syndromes (falls, malnutrition, dementia, severe urinary control issues, absence of fecal control, visual impairment, walking difficulty, pressure ulcers, lack of social support, and weight loss) from claims and EHR data, and the presence of frailty descriptions in clinical notes with a pattern-matching natural language processing (NLP) algorithm. RESULTS: Of the 18,341 patients, we found that 2202 (12%) were described as "frail" in clinical notes. "Frail" patients were older (82.3 ± 6.8 vs 75.9 ± 5.9, p < .001) and had higher rates of healthcare utilization, including number of inpatient hospitalizations and emergency department visits, than the rest of the population (p < .001). "Frail" patients had on average 4.85 ± 1.72 of the ten geriatric syndromes studied, while non-frail patients had 2.35 ± 1.71 (p = .013). Falls, walking difficulty, malnutrition, weight loss, lack of social support and dementia were more highly correlated with frailty descriptions. The most common geriatric syndrome pattern among "frail" patients was a combination of walking difficulty, lack of social support, falls, and weight loss. CONCLUSIONS: Patients identified as "frail" by providers in clinical notes have higher rates of healthcare utilization and more geriatric syndromes than other patients. Certain geriatric syndromes were more highly correlated with descriptions of frailty than others.

Menaquinone biosynthesis potentiates haem toxicity in Staphylococcus aureus.

Staphylococcus aureus is a pathogen that infects multiple anatomical sites leading to a diverse array of diseases. Although vertebrates can restrict the growth of invading pathogens by sequestering iron within haem, S. aureus surmounts this challenge by employing high-affinity haem uptake systems. However, the presence of excess haem is highly toxic, necessitating tight regulation of haem levels. To overcome haem stress, S. aureus expresses the detoxification system HrtAB. In this work, a transposon screen was performed in the background of a haem-susceptible, HrtAB-deficient S. aureus strain to identify the substrate transported by this putative pump and the source of haem toxicity. While a recent report indicates that HrtAB exports haem itself, the haem-resistant mutants uncovered by the transposon selection enabled us to elucidate the cellular factors contributing to haem toxicity. All mutants identified in this screen inactivated the menaquinone (MK) biosynthesis pathway. Deletion of the final steps of this pathway revealed that quinone molecules localizing to the cell membrane potentiate haem-associated superoxide production and subsequent oxidative damage. These data suggest a model in which membrane-associated haem and quinone molecules form a redox cycle that continuously generates semiquinones and reduced haem, both of which react with atmospheric oxygen to produce superoxide.

BioWord: a sequence manipulation suite for Microsoft Word.

BACKGROUND: The ability to manipulate, edit and process DNA and protein sequences has rapidly become a necessary skill for practicing biologists across a wide swath of disciplines. In spite of this, most everyday sequence manipulation tools are distributed across several programs and web servers, sometimes requiring installation and typically involving frequent switching between applications. To address this problem, here we have developed BioWord, a macro-enabled self-installing template for Microsoft Word documents that integrates an extensive suite of DNA and protein sequence manipulation tools. RESULTS: BioWord is distributed as a single macro-enabled template that self-installs with a single click. After installation, BioWord will open as a tab in the Office ribbon. Biologists can then easily manipulate DNA and protein sequences using a familiar interface and minimize the need to switch between applications. Beyond simple sequence manipulation, BioWord integrates functionality ranging from dyad search and consensus logos to motif discovery and pair-wise alignment. Written in Visual Basic for Applications (VBA) as an open source, object-oriented project, BioWord allows users with varying programming experience to expand and customize the program to better meet their own needs. CONCLUSIONS: BioWord integrates a powerful set of tools for biological sequence manipulation within a handy, user-friendly tab in a widely used word processing software package. The use of a simple scripting language and an object-oriented scheme facilitates customization by users and provides a very accessible educational platform for introducing students to basic bioinformatics algorithms.

Directed evolution of a pyruvate aldolase to recognize a long chain acyl substrate.

The use of biological catalysts for industrial scale synthetic chemistry is highly attractive, given their cost effectiveness, high specificity that obviates the need for protecting group chemistry, and the environmentally benign nature of enzymatic procedures. Here we evolve the naturally occurring 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolases from Thermatoga maritima and Escherichia coli, into enzymes that recognize a nonfunctionalized electrophilic substrate, 2-keto-4-hydroxyoctonoate (KHO). Using an in vivo selection based on pyruvate auxotrophy, mutations were identified that lower the K(M) value up to 100-fold in E. coli KDPG aldolase, and that enhance the efficiency of retro-aldol cleavage of KHO by increasing the value of k(cat)/K(M) up to 25-fold in T. maritima KDPG aldolase. These data indicate that numerous mutations distal from the active site contribute to enhanced 'uniform binding' of the substrates, which is the first step in the evolution of novel catalytic activity.

The evolution of a superbug: how Staphylococcus aureus overcomes its unique susceptibility to polyamines.

Polyamines are ubiquitous compounds thought to be synthesized by and required for all life. The manuscript published in this issue by Joshi and colleagues upsets this dogma by identifying several bacterial species that do not make polyamines, and in some cases do not require polyamines for growth. One such species is the significant human pathogen Staphylococcus aureus, which is shown to be uniquely sensitive to polyamines. By unravelling the mechanisms of staphylococcal polyamine toxicity and tolerance, Joshi et al. (2011) provide insights into how the most virulent strains of S. aureus have evolved to be more fit during infection.

Overcoming the heme paradox: heme toxicity and tolerance in bacterial pathogens.

Virtually all bacterial pathogens require iron to infect vertebrates. The most abundant source of iron within vertebrates is in the form of heme as a cofactor of hemoproteins. Many bacterial pathogens have elegant systems dedicated to the acquisition of heme from host hemoproteins. Once internalized, heme is either degraded to release free iron or used intact as a cofactor in catalases, cytochromes, and other bacterial hemoproteins. Paradoxically, the high redox potential of heme makes it a liability, as heme is toxic at high concentrations. Although a variety of mechanisms have been proposed to explain heme toxicity, the mechanisms by which heme kills bacteria are not well understood. Nonetheless, bacteria employ various strategies to protect against and eliminate heme toxicity. Factors involved in heme acquisition and detoxification have been found to contribute to virulence, underscoring the physiological relevance of heme stress during pathogenesis. Herein we describe the current understanding of the mechanisms of heme toxicity and how bacterial pathogens overcome the heme paradox during infection.

Dependence of fluorescence quenching of a poly(p-phenyleneethynylene) polyelectrolyte on the electrostatic and hydrophobic properties of the quencher.

This study investigates the fluorescence quenching of a poly(p-phenyleneethynylene) (1) based polyelectrolyte by positively charged and neutral macromolecules. This work shows that the change in the fluorescence yield of 1 depends on a number of factors, including electrostatic, hydrophobic, and energy transfer interactions with the quencher and also changes in the solution conditions such as concentration and ionic strength. The fluorescence quenching is attributed to the formation of aggregates that form upon addition of different quenchers to a solution of 1 and/or the solution conditions. The extent of 1's aggregation is shown to depend on the type of interaction between the polymer and the quencher, the concentration of the polymer, and the ionic strength of the solution.

Age-dependent photoionization thresholds of melanosomes and lipofuscin isolated from human retinal pigment epithelium cells.

Melanosomes and lipofuscin were isolated from 14-, 59-, and 76-year-old, human retinal pigment epithelium specimens and examined. The morphological features of these samples were studied by scanning electron microscopy and atomic force microscopy, and the photoionization properties were examined by photoelectron emission microscopy. Ovoid- and rod-shaped melanosomes were observed. The size of the granules and the distribution between the two shapes show no significant age-dependent change. However, there is a higher occurrence of irregularly shaped aggregates of small round granules in older samples which suggests degradation or damage to melanosomes occurs with age. The melanosomes from the 14-year-old donor eye are well characterized by a single photoionization threshold, 4.1 eV, while the two older melanosomes exhibit two thresholds around 4.4 and 3.6 eV. Lipofuscin from both young and old cells show two thresholds, 4.4 and 3.4 eV. The similarity of the potentials observed for aged melanosomes and lipofuscin suggest that the lower threshold in the melanosome sample reflects lipofuscin deposited the surface of the melanosome. The amount, however, is not sufficient to alter the density of the melanosome, and therefore these granules do not separate in a sucrose gradient at densities characteristic of the typical melanolipofuscin granule. These data suggest that thin deposits of lipofuscin on the surface of retinal pigment epithelium melanosomes are common in the aged eye and that this renders the melanosomes more pro-oxidant.