Paul Y. Takahashi

A Randomized Controlled Trial of Telemonitoring in Older Adults With Multiple Health Issues to Prevent Hospitalizations and Emergency Department Visits

BACKGROUND Efficiently caring for frail older adults will become an increasingly important part of health care reform;telemonitoring within homes may be an answer to improve outcomes. This study sought to assess differences in hospitalizations and emergency department (ED) visits among older adults using telemonitoring vs usual care. METHODS A randomized controlled trial was performed among adults older than 60 years at high risk for rehospitalization. Participants were randomized to telemonitoring (with daily input) or to patient-driven usual care. Telemonitoring was accomplished by daily biometrics,symptom reporting, and videoconference. The primary outcome was a composite end point of hospitalizations and ED visits in the 12 months following enrollment. Secondary end points included hospitalizations,ED visits, and total hospital days. Intent-to-treat analysis was performed. RESULTS Two hundred five participants were enrolled,with a mean age of 80.3 years. The primary outcome of hospitalizations and ED visits did not differ between the telemonitoring group (63.7%) and the usual care group(57.3%) (P=.35). No differences were observed in secondary end points, including hospitalizations, ED visits,and total hospital days. No significant group differences in hospitalizations and ED visits were found between the pre-enrollment period vs the post-enrollment period. Mortality was higher in the telemonitoring group (14.7%)than in the usual care group (3.9%) (P=.008). CONCLUSIONS Among older patients, telemonitoring did not result in fewer hospitalizations or ED visits. Secondary outcomes demonstrated no significant differences between the telemonitoring group and the usual care group.The cause of greater mortality in the telemonitoring group is unknown.

Inappropriate Medications for Elderly Patients

The use of medications is common in elderly persons, and this population has the highest risk of medication-related problems. Elderly persons are more susceptible to the effects of various medications for a number of reasons. It is well known that polypharmacy is one of the most serious problems in caring for elderly persons; however, many of these patients continue to receive medications that have an increased risk of causing harm. In 1991, an important article was published about inappropriate medication use in the elderly population. This article raised awareness of the problem and presented explicit criteria for determining which medications were inappropriate for elderly patients residing in long-term care facilities. This list of drugs is still used for evaluating medications taken by elderly persons and for determining whether satisfactory prescribing practices are being used. We reviewed the medications described as inappropriate for elderly persons and searched the scientific literature to determine whether evidence exists to defend or refute the labeling of particular drugs. At times, evidence was difficult to find, and many of the original studies were dated. For most medications listed as inappropriate, we found evidence to support these designations.

Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time-using genomic data to individualize treatment protocol.

OBJECTIVE To report the design and implementation of the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment protocol that was developed to test the concept that prescribers can deliver genome-guided therapy at the point of care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated into the electronic medical record (EMR). PATIENTS AND METHODS We used a multivariate prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR. RESULTS The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for International Classification of Diseases, Ninth Revision codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance. CONCLUSION This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice.

The Mayo Clinic Biobank: A Building Block for Individualized Medicine

OBJECTIVE To report the design and implementation of the first 3 years of enrollment of the Mayo Clinic Biobank. PATIENTS AND METHODS Preparations for this biobank began with a 4-day Deliberative Community Engagement with local residents to obtain community input into the design and governance of the biobank. Recruitment, which began in April 2009, is ongoing, with a target goal of 50,000. Any Mayo Clinic patient who is 18 years or older, able to consent, and a US resident is eligible to participate. Each participant completes a health history questionnaire, provides a blood sample, and allows access to existing tissue specimens and all data from their Mayo Clinic electronic medical record. A community advisory board provides ongoing advice and guidance on complex decisions. RESULTS After 3 years of recruitment, 21,736 individuals have enrolled. Fifty-eight percent (12,498) of participants are female and 95% (20,541) of European ancestry. Median participant age is 62 years. Seventy-four percent (16,171) live in Minnesota, with 42% (9157) from Olmsted County, where the Mayo Clinic in Rochester, Minnesota, is located. The 5 most commonly self-reported conditions are hyperlipidemia (8979, 41%), hypertension (8174, 38%), osteoarthritis (6448, 30%), any cancer (6224, 29%), and gastroesophageal reflux disease (5669, 26%). Among patients with self-reported cancer, the 5 most common types are nonmelanoma skin cancer (2950, 14%), prostate cancer (1107, 12% in men), breast cancer (941, 4%), melanoma (692, 3%), and cervical cancer (240, 2% in women). Fifty-six percent (12,115) of participants have at least 15 years of electronic medical record history. To date, more than 60 projects and more than 69,000 samples have been approved for use. CONCLUSION The Mayo Clinic Biobank has quickly been established as a valuable resource for researchers.

Use of an electronic administrative database to identify older community dwelling adults at high-risk for hospitalization or emergency department visits: The elders risk assessment index

BackgroundThe prevention of recurrent hospitalizations in the frail elderly requires the implementation of high-intensity interventions such as case management. In order to be practically and financially sustainable, these programs require a method of identifying those patients most at risk for hospitalization, and therefore most likely to benefit from an intervention. The goal of this study is to demonstrate the use of an electronic medical record to create an administrative index which is able to risk-stratify this heterogeneous population.MethodsWe conducted a retrospective cohort study at a single tertiary care facility in Rochester, Minnesota. Patients included all 12,650 community-dwelling adults age 60 and older assigned to a primary care internal medicine provider on January 1, 2005. Patient risk factors over the previous two years, including demographic characteristics, comorbid diseases, and hospitalizations, were evaluated for significance in a logistic regression model. The primary outcome was the total number of emergency room visits and hospitalizations in the subsequent two years. Risk factors were assigned a score based on their regression coefficient estimate and a total risk score created. This score was evaluated for sensitivity and specificity.ResultsThe final model had an AUC of 0.678 for the primary outcome. Patients in the highest 10% of the risk group had a relative risk of 9.5 for either hospitalization or emergency room visits, and a relative risk of 13.3 for hospitalization in the subsequent two year period.ConclusionsIt is possible to create a screening tool which identifies an elderly population at high risk for hospital and emergency room admission using clinical and administrative data readily available within an electronic medical record.

The aging male hypothalamic–pituitary–gonadal axis: Pulsatility and feedback

Aging results in insidious decremental changes in hypothalamic, pituitary and gonadal function. The foregoing three main anatomic loci of control are regulated by intermittent time-delayed signal exchange, principally via gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and testosterone/estradiol (Te/E(2)). A mathematical framework is required to embody these dynamics. The present review highlights integrative adaptations in the aging male hypothalamic-pituitary-gonadal axis, as assessed by recent objective ensemble models of the axis as a whole.

Biobanks and personalized medicine

We provide a mini‐review of how biobanks can support clinical genetics in the era of personalized medicine. We discuss types of biobanks, including disease specific and general biobanks not focused on one disease. We present considerations in setting up a biobank, including consenting and governance, biospecimens, risk factor and related data, informatics, and linkage to electronic health records for phenotyping. We also discuss the uses of biobanks and ongoing considerations, including genotype‐driven recruitment, investigations of gene–environment associations, and the re‐use of data generated from studies. Finally, we present a brief discussion of some of the unresolved issues, such as return of research results and sustaining biobanks over time. In summary, carefully designed biobanks can provide critical research and infrastructure support for clinical genetics in the era of personalized medicine.

A randomized controlled trial of telemonitoring in older adults with multiple chronic conditions: the Tele-ERA study

BackgroundOlder adults with multiple chronic illnesses are at risk for worsening functional and medical status and hospitalization. Home telemonitoring may help slow this decline. This protocol of a randomized controlled trial was designed to help determine the impact of home telemonitoring on hospitalization. The specific aim of the study reads as follows: to determine the effectiveness of home telemonitoring compared with usual care in reducing the combined outcomes of hospitalization and emergency department visits in an at-risk population 60 years of age or older.Methods/DesignTwo-hundred patients with the highest 10% Mayo Clinic Elder Risk Assessment scores will be randomly assigned to one of two interventions. Home telemonitoring involves the use of a computer device, the Intel Health Guide, which records biometric and symptom data from patients in their homes. This information is monitored by midlevel providers associated with a primary care medical practice. Under the usual care scenario, patients make appointments with their providers as problems arise and use ongoing support such as a 24-hour nurse line.Patients will have initial evaluations of gait and quality of life using instruments such as the SF-12 Health Survey, the Kokmen Short Test of Mental Status, and the PHQ-9 health questionnaire. Patients will be followed for 1 year for primary outcomes of hospitalizations and emergency department visits. Secondary analysis will include quality of life, compliance with the device, and attitudes about telemonitoring. Sample size is based on an 80% power to detect a 36% difference between the two groups. The primary analysis will involve Cox proportional time-to-event analysis. Secondary analysis will use t-test comparisons for continuous variables and the chi square test for proportional analysis.DiscussionPatients randomized to home telemonitoring will have daily assessments of their health status using the device. Registered nurse monitoring will assess any change in status followed by videoconferencing by a mid-level provider. We obtained trial registration and Institutional Review Board approval.Trial registrationTrial registration number through http://www.clinicaltrials.gov:%20NCT01056640.

Older men exhibit reduced efficacy of and heightened potency downregulation by intravenous pulses of recombinant human LH: A study in 92 healthy men

Direct sampling of the human spermatic veins has disclosed concomitant LH and testosterone (T) pulses, suggesting pulsatile LH concentration-dependent stimulation of T secretion. However, studies to date have examined this hypothesis using only pharmacological stimulation with hCG. The present study tests the hypothesis that age is marked by decreased T secretory responses to repeated near-physiological iv pulses of recombinant human LH administered in a Clinical Translational Science Center. Participants included 92 healthy men aged 18-75 yr with BMI 18-34 kg/m(2). The contribution of endogenous LH pulses was minimized by combined injection of a selective GnRH receptor antagonist sc and successive pulses of biosynthetic LH iv. A new analytical dose response model was applied to estimate the properties of exogenous LHs drive of T secretion. Regression of LH-T dose response potency estimates on age showed that the efficacy of pulses of biosynthetic LH progressively decreased with age (P = 0.014, r = 0.26). Testis sensitivity to exogenous LH pulses also declined with age (P = 0.011, r = 0.27). Moreover, estimated Leydig cell downregulation by LH pulses rose significantly with age (P = 0.039, r = 0.22). These outcomes were selective, since the recovery potency of infused LH was not affected by age but was reduced by increasing BMI (P = 0.011, r = 0.27). Assuming stable bioactivity of infused recombinant human LH, these novel data indicate that factors associated with age and BMI attenuate LH efficacy and testis sensitivity and augment Leydig cell downregulation in healthy men.

Wound Care for Elderly Patients: Advances and Clinical Applications for Practicing Physicians

Chronic ulcers (wounds) are commonly encountered in medical practice, particularly in elderly patients who have chronic medical conditions. Health care providers must be adept at diagnosing chronic ulcers and optimizing medical treatment. We describe the best medical practice for the 4 common types of chronic ulcers: pressure ulcers, ischemic ulcers, venous ulcers, and neuropathic ulcers. We emphasize the importance of nutrition and proper wound care as a foundation for the management of all chronic ulcers. There is a unique therapeutic goal for each chronic ulcer. Pressure relief should be provided for both pressure ulcers and neuropathic ulcers. Ischemic ulcers require revascularization. Patients with venous ulcers need adequate edema control. We outline advances in each of these areas and discuss the newest developments in wound care, including growth factors, hyperbaric oxygen, and vacuum-assisted devices. Chronic ulcers in elderly patients can heal with proper diagnosis and good medical care.