Authigenic iron oxide proxies for marine zinc over geological time and implications for eukaryotic metallome evolution.

Here, we explore enrichments in paleomarine Zn as recorded by authigenic iron oxides including Precambrian iron formations, ironstones, and Phanerozoic hydrothermal exhalites. This compilation of new and literature-based iron formation analyses track dissolved Zn abundances and constrain the magnitude of the marine reservoir over geological time. Overall, the iron formation record is characterized by a fairly static range in Zn/Fe ratios throughout the Precambrian, consistent with the shale record (Scott et al., 2013, Nature Geoscience, 6, 125-128). When hypothetical partitioning scenarios are applied to this record, paleomarine Zn concentrations within about an order of magnitude of modern are indicated. We couple this examination with new chemical speciation models to interpret the iron formation record. We present two scenarios: first, under all but the most sulfidic conditions and with Zn-binding organic ligand concentrations similar to modern oceans, the amount of bioavailable Zn remained relatively unchanged through time. Late proliferation of Zn in eukaryotic metallomes has previously been linked to marine Zn biolimitation, but under this scenario the expansion in eukaryotic Zn metallomes may be better linked to biologically intrinsic evolutionary factors. In this case, zinc's geochemical and biological evolution may be decoupled and viewed as a function of increasing need for genome regulation and diversification of Zn-binding transcription factors. In the second scenario, we consider Archean organic ligand complexation in such excess that it may render Zn bioavailability low. However, this is dependent on Zn-organic ligand complexes not being bioavailable, which remains unclear. In this case, although bioavailability may be low, sphalerite precipitation is prevented, thereby maintaining a constant Zn inventory throughout both ferruginous and euxinic conditions. These results provide new perspectives and constraints on potential couplings between the trajectory of biological and marine geochemical coevolution.

Prevention of iatrogenic illness: adverse drug reactions and nosocomial infections in hospitalized older adults.

Adverse drug reactions and nosocomial infections are two important aspects of iatrogenesis in hospitalized older adults. Adverse drug reactions are related to changes in pharmacodynamics and pharmacokinetics that occur with aging as well as polypharmacy. Strategies for limiting iatrogenesis due to medications are discussed. Nosocomial infections continue to complicate older inpatients' care despite advances in understanding and treating institutional infections. In particular, urinary tract infections, nosocomial pneumonias, and Clostridium difficile-associated diarrhea are potentially preventable.

Behavioral disturbance and impairment of executive functions among the elderly.

Among the elderly, measures of general cognitive ability are not consistently related to the capacity for independent functioning. Some elder patients perform well on global tests of cognition, yet demonstrate behavior that is disruptive to their lives and those of their families. The genesis of these behavior problems is poorly understood, and caregivers, both professional and non-professional, frequently attribute their behavior to wilful misconduct. We propose that there are sufficient data concerning the so-called executive functions of the brain and their impairment in both normal aging and various types of dementia, to support the hypothesis that many behavioral disturbances among demented older adults are a function of different degrees of loss of the capacity to engage in purposeful, goal-directed activity. The executive functions are complex, and include the capacities for planning, organization and active problem solving, and the ability to engage in purposeful, goal-directed behavior. Impaired executive functioning is common in dementia, but also may be present in the context of an age-related decline in the speed and capacity of information processing and varying levels of general cognitive impairment. We review data in support of this model, and discuss a patient whose case illustrates deficits in the independent regulation of behavior, an important executive function mediated primarily by the prefrontal area. In the discussion we address several hypotheses suggested by this perspective.

Incidence of digoxin toxicity in outpatients.

The incidence of digoxin toxicity among patients in hospitals has declined in recent years. To evaluate whether a similar decline has occurred in ambulatory care, we reviewed randomly selected medical records for 183 outpatients receiving ongoing treatment with digoxin at 10 urban and rural Department of Veterans Affairs Medical Centers in the Rocky Mountain region. The prevalence of traditional risk factors for digoxin toxicity--elevated serum digoxin and serum creatinine levels, hypokalemia, and a new prescription of an interacting drug-was established from computerized laboratory and pharmacy records. Of the 183 patients, 50 (27.3%) had one or more risk factors for digoxin toxicity: serum digoxin levels were elevated in 13.6% of patients in whom a level was obtained, with hypokalemia in 14.3%, elevated creatinine levels in 17.9%, and possible drug interactions in 5.5% of patients over a 1-year period. Nevertheless, digoxin toxicity occurred in only 2 persons (1.1% or 1.4 per 100 patient-years of treatment). We conclude that digoxin toxicity was rare in this group of outpatients, even in persons presumed to be at high risk because of metabolic abnormalities, increased digoxin concentrations, or the use of interacting drugs. The low rate of digoxin toxicity in outpatients parallels the decline in the incidence of toxicity observed in hospital-based studies.

The effect of prescription size on acquisition of maintenance medications.

OBJECTIVE: To determine whether large prescriptions (> or = 90 days' supplies) enhance the acquisition of maintenance medications by patients. DESIGN: Study 1: multisite, retrospective cohort study evaluating outpatient digoxin use. Study 2: single-site, retrospective cohort study to confirm Study 1. SETTING: Study 1: Ten Veterans Affairs Medical Centers in the Rocky Mountain region. Study 2: The only facility from Study 1 (site C) that dispensed large prescriptions of maintenance medications. PATIENTS: Randomly selected outpatients receiving two or more digoxin prescriptions (n = 176 in Study 1, n = 114 in Study 2). INTERVENTION: None. RESULTS: The main outcome measure was the proportion of prescribed doses of maintenance medications obtained. In Study 1, patients who received at least one large digoxin prescription obtained a mean of 137.2% of their prescribed digoxin doses over a mean of nine months, compared with 91.3% for patients who received only small prescriptions of < 90 days' supplies (p = 0.02). Patients receiving large prescriptions were more likely to obtain at least 100% of their prescribed amounts of digoxin (adjusted OR = 11.4, 95% CI = 1.3-96.8, p = 0.03). At site C, patients in Study 1 obtained a mean of 129.0% of all maintenance drugs given in large supplies, compared with 95.2% of drugs prescribed only in small supplies (p = 0.006). In Study 2, acquisition of digoxin increased progressively from 89.7% among individuals who received only small digoxin prescriptions to 113.0% for those who received only large supplies (p = 0.002), over a mean of 14 months. CONCLUSIONS: Large prescriptions facilitate the acquisition of maintenance medications but may lead to oversupplies, while small prescriptions impose a barrier to obtaining these drugs.

Mid-career faculty development awards in geriatrics: does retraining work?

OBJECTIVE: To evaluate the success of a mid-career physicians faculty retraining in geriatric medicine. DESIGN: Written survey of participants in the John Hartford Foundation's Mid-Career Faculty Development Program (1984-1988). SETTING: Four well established geriatric fellowship training programs. PARTICIPANTS: The 29 physicians who received John Hartford Foundation awards. RESULTS: Twenty-one (87%) of 24 respondents felt that the fellowship year had either a "major" or "significant" impact on their careers, and 87% also spend a significant portion of their time training others in geriatrics. CONCLUSION: This 4-year experiment in mid-career faculty retraining in geriatrics suggests that this approach is a viable alternative to traditional 2-year fellowships for helping to reduce the shortage of faculty in geriatric medicine.

Reliabilities, norms and factor structure of the Behavioral Dyscontrol Scale.

This is a report on the statistical properties of a research and clinical measure of cognitive and behavioral functioning, which has so far demonstrated utility among elderly persons. This instrument, the Behavioral Dyscontrol Scale, is adapted from Luria's approach to the assessment of frontal lobe dysfunction. The scale shows high internal consistency and very good interrater reliability. In a clinically stable, elderly population, test-retest reliability is high. Normative data are presented for three different samples: 47 young adults, 141 cognitively normal elderly persons, and our total elderly sample of 229. A principal components analysis yielded 3 factors consistent with Luria's theory.

Prediction of independent functioning and behavior problems in geriatric patients.

Folstein's Mini Mental State Exam, a test assessing the capacity to perform novel and/or repetitive motor tasks (Behavioral Dyscontrol Scale) and a brief measure of working memory were used in a sample of 50 male Veterans Affairs geriatric clinic patients who ranged in age from 63 to 105 (mean, 80.1). The purpose of this study was to attempt to predict the patients' capacity to regulate their behavior independently. We hypothesized that frontal lobe disorders often impair a patient's ability to function autonomously and that the Behavioral Dyscontrol Scale, a measure of frontal lobe impairment, would best predict the capacity for independent regulation of purposeful behavior. Therefore, we examined the relationship of the Behavioral Dyscontrol Scale with spouses' and caregivers' ratings of patients' independent living skills, and with behaviors that interfere with independent functioning. The results of hierarchial regression analyses indicated that the Behavioral Dyscontrol Scale was the only predictor of functional autonomy and was the best predictor of both impulsivity and apathy among geriatric patients. The Behavioral Dyscontrol Scale appears to assess a different functional domain than do the MMSE and similar measures, which rely heavily on the evaluation of orientation and gross cognitive status.

Evaluation of weight loss in the elderly.

Weight loss among elderly patients is a common clinical problem that may herald numerous medical and psychosocial disorders. Up to 50% of patients claiming weight loss will not have their complaint corroborated by medical records or family members. Since modest weight loss may occur as a physiologic change with advancing age, the practicing physician must have a working definition of pathologic weight loss that triggers an appropriate diagnostic evaluation. After a careful initial history, physical exam, and a limited laboratory test battery, physicians will identify most patients with physical causes for weight loss. Like many other geriatric syndromes, weight loss may require the identification and correction of multiple contributing factors.

Binding the elderly: a prospective study of the use of mechanical restraints in an acute care hospital.

Little information exists on the use of mechanical restraints among nonpsychiatric inpatients. This prospective study evaluates their use among consecutive medical and surgical admissions to an acute care hospital. Daily direct observation of patients and hospital record review provided data on potential predictors of restraint, reasons for their application, complications, and outcome. Cox regression analysis was used to calculate relative risk of restraint while adjusting for duration of hospitalization as well as other variables. Restraints were applied to 37 (17%) of the 222 study patients. Restrained patients were eight times more likely to die during hospitalization (24% v 3%; P less than 0.01). Abnormal mental status exam, diagnosis of dementia, surgery, and presence of monitoring and support devices (eg, intravenous lines) were statistically significant independent predictors of restraint. Mechanical restraint is a common occurrence among nonpsychiatric inpatients particularly those with impaired mentation, requirement for surgery, or intensive medical intervention. Identification of medical and surgical patients at risk for restraint may reduce the use of these devices by concentrating surveillance and prevention on this group.

Restraining the elderly patient.

The use of chemical and mechanical restraints to control the behavior of cognitively impaired elderly patients is controversial. The issue frequently arises in nonpsychiatric as well as psychiatric hospital and chronic care settings. The lack of specific judicial and legislative mandates has left the decision to use restraints in the hands of hospital and nursing home administrators and medical personnel. Attention to the proven risks and potential benefits of restraints in the elderly patient may help to limit unnecessary application of these devices.

Academic affiliation with a nursing home. Impact on patient outcome.

In a prospective study, 46 patients discharged from a teaching hospital to a "teaching unit" nursing home, where primary medical care was provided by faculty geriatricians, medical students, and medical housestaff, were compared with 78 similar patients discharged to one of five community nursing homes without a teaching affiliation. At the time of hospital discharge, patients were determined to have a terminal, rehabilitative, or long stay prognosis based on a review of hospital discharge summaries using specific criteria. Among 34 study and 55 control patients with a long stay prognosis, ten of the study group compared with seven of the control group returned home (P = .03). Seven of 34 long stay patients in the study group were rehospitalized, while 15 of a matched control group of 34 required hospitalization (P = .04). There was no increase in mortality or emergency service use in the study population. Patients considered to be terminal or rehabilitative showed no difference in ultimate outcome or hospital use. In the study group patients experienced an average reduction in total medications prescribed from 6.2 to 5.3, while patients in the control group had an increase from 5.4 medications prescribed to 7.6 (P less than .001). Of 16 study patients discharged from the teaching unit nursing home, all remained home at least three months after discharge; only 12 of 18 control group patients discharged from the nursing home remained at home at three months (P less than .01). Long-term care by geriatric faculty, students, and housestaff appeared to have favorably influenced patient outcomes.

A mobile internal medicine clinic.

The Denver Veterans Administration Medical Center (DVAMC) established a mobile internal medicine clinic (MediVAn) to provide access to primary care for veterans living more than fifty miles from the center and to study the costs of such an outreach program. A fully equipped van staffed by an internist visited four Colorado cities weekly for scheduled appointments. In the first two years of operation there were 4,655 visits by 766 veterans with a mean age of 56 years, with 3.9 diagnoses, and receiving 3.0 medicines. The cost per MediVAn visit was $68, compared with $67 per outpatient visit at DVAMC. We conclude that a mobile medical clinic is a convenient method of delivering primary care over distances and is comparable in cost to outpatient hospital visits.

Trigeminal neuropathy--new observations.

Five cases of trigeminal neuropathy of the idiopathic variety are reported; one patient had an associated unilateral hypoglossal neuropathy with fasciculations and wasting of the ipsilateral half of the tongue. No demonstrable cause was found with the usual laboratory and neuroradiological examinations. Four of the patients underwent retromastoid craniectomy, and the microsurgical observations of the cerebellopontine angle are noted. The superior cerebellar artery (three cases) or anterior inferior cerebellar artery (one case) was found to be stretching the trigeminal nerve in all four case. Microvascular decompression provided pain relief and sensory recovery or improvement in all patients operated upon. In one case, the hypoglossal nerve was also found to be distorted by an arterial loop of a medullary artery; decompression of the loop resulted in complete recovery of hypoglossal function on the affected side. In cases of persistent idiopathic trigeminal neuropathy with or without intractable pain, retromastoid craniectomy with microvascular decompression of the 5th nerve is a therapeutic alternative. (Neurosurgery, 7: 347-351, 1980).