Cohort Profile: The Precipitating Events Project (PEP Study).

The Precipitating Events Project (PEP Study) is an ongoing longitudinal study of 754 nondisabled community-living persons age 70 years or older who were members of a large health plan in greater New Haven, Connecticut, USA. The study was established to rigorously evaluate the epidemiology of disability in older persons and to elucidate the role of intervening illnesses and injuries on the disabling process. Of the eligible members, 75.2% agreed to participate and were enrolled between March 1998 and October 1999. Participants have completed comprehensive home-based assessments at 18-month intervals and have been interviewed monthly over the phone with a completion rate of 99%. Detailed participant-level data on health care utilization are obtained annually through linkages with Medicare claims. Through June 2019, 702 (93.1%) participants have died after a median of 109 months, while 43 (5.7%) have dropped out of the study after a median of 27 months. Death certificates are available for all decedents. To date, 117 original reports have been published using data from the PEP Study, including many focusing on other high priority areas such as end of life, frailty, depressive symptoms, aging stereotypes, pain, sleep, and methodologic research. The PEP Study welcomes proposals to access data for meritorious analyses from qualified investigators.

Bayesian hierarchical modeling for a non-randomized, longitudinal fall prevention trial with spatially correlated observations.

Because randomization of participants is often not feasible in community-based health interventions, non-randomized designs are commonly employed. Non-randomized designs may have experimental units that are spatial in nature, such as zip codes that are characterized by aggregate statistics from sources like the U.S. census and the Centers for Medicare and Medicaid Services. A perennial concern with non-randomized designs is that even after careful balancing of influential covariates, bias may arise from unmeasured factors. In addition to facilitating the analysis of interventional designs based on spatial units, Bayesian hierarchical modeling can quantify unmeasured variability with spatially correlated residual terms. Graphical analysis of these spatial residuals demonstrates whether variability from unmeasured covariates is likely to bias the estimates of interventional effect. The Connecticut Collaboration for Fall Prevention is the first large-scale longitudinal trial of a community-wide healthcare intervention designed to prevent injurious falls in older adults. Over a two-year evaluation phase, this trial demonstrated a rate of fall-related utilization at hospitals and emergency departments by persons 70 years and older in the intervention area that was 11 per cent less than that of the usual care area, and a 9 per cent lower rate of utilization from serious injuries. We describe the Bayesian hierarchical analysis of this non-randomized intervention with emphasis on its spatial and longitudinal characteristics. We also compare several models, using posterior predictive simulations and maps of spatial residuals.

Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients.

BACKGROUND: Diphenhydramine hydrochloride is a commonly prescribed medicine in hospitalized patients, but its adverse effects on older patients remain unclear. METHODS: We enrolled 426 hospitalized medical patients aged 70 years or older in a prospective cohort study in a university hospital. Measurements included baseline and daily assessments including Mini-Mental State Examination scores, Confusion Assessment Method ratings, direct observations for medical devices (urinary catheter or physical restraints), and blinded medical record extractions for diphenhydramine use. RESULTS: Of the 426 patients, 114 (27%) received diphenhydramine during hospitalization and shared similar baseline characteristics including age, sex, delirium risk, and Mini-Mental State Examination scores compared with nonexposed patients. The diphenhydramine-exposed group was at an increased risk for any delirium symptoms (relative risk [RR], 1.7; 95% confidence interval [CI], 1.3-2.3) and for individual delirium symptoms, including inattention (RR, 3.0; 95% CI, 1.5-5.9), disorganized speech (RR, 5.5; 95% CI, 1.0-29.8), and altered consciousness (RR, 3.1; 95% CI, 1.6-6.1). Exposed patients also had increased risk for urinary catheter placement (RR, 2.5; 95% CI, 1.0-6.0) and longer median length of stay (7 vs 6 days; P =.009). A dose-response relationship was demonstrated for most adverse outcomes. Overall, 24% of diphenhydramine doses were administered inappropriately. CONCLUSIONS: Diphenhydramine administration in older hospitalized patients is associated with an increased risk of cognitive decline and other adverse effects with a dose-response relationship. Careful review of its use is necessary in this vulnerable population.

Multicomponent targeted intervention to prevent delirium in hospitalized older patients: what is the economic value?

INTRODUCTION: Delirium, or acute confusional state, is a common and serious occurrence among hospitalized older persons. Current estimates suggest that delirium complicates hospital stays for more than 2.3 million older persons each year, involving more than 17.5 million hospital days and accounting for more than $4 billion (1994 dollars) of Medicare expenditures. A 40% reduction was recently reported in the risk for delirium among hospitalized older persons receiving a multicomponent targeted risk factor intervention (MTI) strategy to prevent delirium, compared with subjects receiving usual hospital care.1 Before recommending that this preventive strategy be implemented in clinical practice, however, the cost implications must be thoroughly examined as well. METHODS: The present analysis performs net cost evaluations of the MTI for the prevention of delirium among hospitalized patients. Hospital charge and cost-to-charge ratio data are linked to a database of 852 subjects, who were treated with MTI or usual care. Multivariable regression methods were used to help isolate the impact of MTI on hospital costs. These results were then combined with our earlier work on the impact of the MTI on delirium prevention to assess the cost effectiveness of this intervention. RESULTS: The MTI significantly reduced nonintervention costs among subjects at intermediate risk for developing delirium, but not among subjects at high risk. When MTI intervention costs were included, MTI had no significant effect on overall health care costs in the intermediate risk cohort, but raised overall costs in the high risk group. CONCLUSIONS: Because the MTI prevented delirium in the intermediate risk group without raising costs, the conclusion reached is that it is a cost effective treatment option for patients at intermediate risk for developing delirium. In contrast, the results suggest that the MTI is not cost effective for subjects at high risk.

The Hospital Elder Life Program: a model of care to prevent cognitive and functional decline in older hospitalized patients. Hospital Elder Life Program.

OBJECTIVES: To describe the Hospital Elder Life Program, a new model of care designed to prevent functional and cognitive decline of older persons during hospitalization. PROGRAM STRUCTURE AND PROCESS: All patients aged > or =70 years on specified units are screened on admission for six risk factors (cognitive impairment, sleep deprivation, immobility, dehydration, vision or hearing impairment). Targeted interventions for these risk factors are implemented by an interdisciplinary team-including a geriatric nurse specialist, Elder Life Specialists, trained volunteers, and geriatricians--who work closely with primary nurses. Other experts provide consultation at twice-weekly interdisciplinary rounds. INTERVENTION: Adherence is carefully tracked. Quality assurance procedures and performance reviews are an integral part of the program. PROGRAM OUTCOMES: To date, 1,507 patients have been enrolled during 1,716 hospital admissions. The overall intervention adherence rate was 89% for at least partial adherence with all interventions during 37,131 patient-days. Our results indicate that only 8% of admissions involved patients who declined by 2 or more points on MMSE and only 14% involved patients who declined by 2 or more points on ADL score. Comparative results for the control group from the clinical trial were 26% and 33%, and from previous studies 14 to 56% and 34 to 50% for cognitive and functional decline, respectively. Effectiveness of the program for delirium prevention and of the program's nonpharmacologic sleep protocol have been demonstrated previously. CONCLUSIONS: These results suggest that the Hospital Elder Life Program successfully prevents cognitive and functional decline in at-risk older patients. The program is unique in its hospital-wide focus; in providing skilled staff and volunteers to implement interventions; and in targeting practical interventions toward evidence-based risk factors. Future studies are needed to evaluate cost-effectiveness and longterm outcomes of the program as well as its effectiveness in non-hospital settings.

A multicomponent intervention to prevent delirium in hospitalized older patients.

BACKGROUND: Since in hospitalized older patients delirium is associated with poor outcomes, we evaluated the effectiveness of a multicomponent strategy for the prevention of delirium. METHODS: We studied 852 patients 70 years of age or older who had been admitted to the general-medicine service at a teaching hospital. Patients from one intervention unit and two usual-care units were enrolled by means of a prospective matching strategy. The intervention consisted of standardized protocols for the management of six risk factors for delirium: cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration. Delirium, the primary outcome, was assessed daily until discharge. RESULTS: Delirium developed in 9.9 percent of the intervention group as compared with 15.0 percent of the usual-care group, (matched odds ratio, 0.60; 95 percent confidence interval, 0.39 to 0.92). The total number of days with delirium (105 vs. 161, P=0.02) and the total number of episodes (62 vs. 90, P=0.03) were significantly lower in the intervention group. However, the severity of delirium and recurrence rates were not significantly different. The overall rate of adherence to the intervention was 87 percent, and the total number of targeted risk factors per patient was significantly reduced. Intervention was associated with significant improvement in the degree of cognitive impairment among patients with cognitive impairment at admission and a reduction in the rate of use of sleep medications among all patients. Among the other risk factors per patient there were trends toward improvement in immobility, visual impairment, and hearing impairment. CONCLUSIONS: The risk-factor intervention strategy that we studied resulted in significant reductions in the number and duration of episodes of delirium in hospitalized older patients. The intervention had no significant effect on the severity of delirium or on recurrence rates; this finding suggests that primary prevention of delirium is probably the most effective treatment strategy.

Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third National Acute Spinal Cord Injury randomized controlled trial.

OBJECT: A randomized double-blind clinical trial was conducted to compare neurological and functional recovery and morbidity and mortality rates 1 year after acute spinal cord injury in patients who had received a standard 24-hour methylprednisolone regimen (24MP) with those in whom an identical MP regimen had been delivered for 48 hours (48MP) or those who had received a 48-hour tirilazad mesylate (48TM) regimen. METHODS: Patients for whom treatment was initiated within 3 hours of injury showed equal neurological and functional recovery in all three treatment groups. Patients for whom treatment was delayed more than 3 hours experienced diminished motor function recovery in the 24MP group, but those in the 48MP group showed greater 1-year motor recovery (recovery scores of 13.7 and 19, respectively, p=0.053). A greater percentage of patients improving three or more neurological grades was also observed in the 48MP group (p=0.073). In general, patients treated with 48TM recovered equally when compared with those who received 24MP treatments. A corresponding recovery in self care and sphincter control was seen but was not statistically significant. Mortality and morbidity rates at 1 year were similar in all groups. CONCLUSIONS: For patients in whom MP therapy is initiated within 3 hours of injury, 24-hour maintenance is appropriate. Patients starting therapy 3 to 8 hours after injury should be maintained on the regimen for 48 hours unless there are complicating medical factors.

Maternal anthropometric factors and risk of primary cesarean delivery.

OBJECTIVES: This study examined absolute and proportional gestational weight gain and prepregnancy body mass index as predictors of primary cesarean delivery. METHODS: Data were derived from a prospective study of pregnancy outcome risk factors in 2301 women in greater New Haven, Conn, who had singleton deliveries by primary cesarean (n = 312) or vaginal delivery (n = 1989) and for whom height, prepregnancy weight, and weight gain were available. Women were divided into 4 body mass index groups (underweight, low average, high average, and obese) and further subdivided into 8 groups according to median proportional or absolute weight gain. RESULTS: Risk of cesarean delivery increased with increasing body mass index and gestational weight gain greater than the median for one's body mass index. Proportional weight gain was more predictive of cesarean delivery than absolute weight gain. Underweight women gaining more than 27.8% of their prepregnancy weight had a 2-fold adjusted relative risk of cesarean delivery. CONCLUSIONS: Proportional weight gain is an important predictor of cesarean delivery for underweight women; high body mass index is also predictive of increased risk.

Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study.

OBJECTIVE: To compare the efficacy of methylprednisolone administered for 24 hours with methyprednisolone administered for 48 hours or tirilazad mesylate administered for 48 hours in patients with acute spinal cord injury. DESIGN: Double-blind, randomized clinical trial. SETTING: Sixteen acute spinal cord injury centers in North America. PATIENTS: A total of 499 patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury. INTERVENTION: All patients received an intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients in the 24-hour regimen group (n=166) received a methylprednisolone infusion of 5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167) received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of tirilazad mesylate every 6 hours for 48 hours. MAIN OUTCOME MEASURES: Motor function change between initial presentation and at 6 weeks and 6 months after injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks and 6 months. RESULTS: Compared with patients treated with methylprednisolone for 24 hours, those treated with methylprednisolone for 48 hours showed improved motor recovery at 6 weeks (P=.09) and 6 months (P=.07) after injury. The effect of the 48-hour methylprednisolone regimen was significant at 6 weeks (P=.04) and 6 months (P=.01) among patients whose therapy was initiated 3 to 8 hours after injury. Patients who received the 48-hour regimen and who started treatment at 3 to 8 hours were more likely to improve 1 full neurologic grade (P=.03) at 6 months, to show more improvement in 6-month FIM (P=.08), and to have more severe sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group and the tirilazad group, but other complications and mortality (P=.97) were similar. Patients treated with tirilazad for 48 hours showed motor recovery rates equivalent to patients who received methylprednisolone for 24 hours. CONCLUSIONS: Patients with acute spinal cord injury who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone is initiated 3 to 8 hours after injury, patients should be maintained on steroid therapy for 48 hours.

Predictors of mortality and institutionalization after hip fracture: the New Haven EPESE cohort. Established Populations for Epidemiologic Studies of the Elderly.

OBJECTIVES: Hip fractures can have devastating effects on the lives of older individuals. We determined the frequency of occurrence of hip fracture and the baseline factors predicting death and institutionalization at 6 months after hip fracture. METHODS: A representative cohort of 2812 individuals aged 65 years and older was followed prospectively for 6 years. Hip fractures were identified, and the occurrence of death and institutionalization within 6 months of the fracture was determined. Prefracture information on physical and mental function, social support, and demographic features and in-hospital data on comorbid diagnoses, fracture site, and complications were analyzed to determine predictors of death and institutionalization after hip fracture. RESULTS: Of 120 individuals suffering a hip fracture, 22 (18%) died within 6 months and 35 (29%) were institutionalized at 6 months. The predictors of death in multiple logistic regression included fracture site, a high number of comorbid conditions, a high number of complications, and poor baseline mental status. The primary predictor of institutionalization was poor baseline mental status. CONCLUSIONS: The frequency of death, institutionalization, and loss of function after hip fracture should prompt a reevaluation of the current approach to this problem.

Emotional support and survival after myocardial infarction. A prospective, population-based study of the elderly.

OBJECTIVE: To compare the survival of elderly patients hospitalized for acute myocardial infarction who have emotional support with that of patients who lack such support, while controlling for severity of disease, comorbidity, and functional status. DESIGN: A prospective, community-based cohort study. SETTING: Two hospitals in New Haven, Connecticut. PATIENTS: Men (n = 100) and women (n = 94) 65 years of age or more hospitalized for acute myocardial infarction between 1982 and 1988. MEASUREMENTS: Social support, age, gender, race, education, marital status, living arrangements, presence of depression, smoking history, weight, and physical function were assessed prospectively using questionnaires. The presence of congestive heart failure, pulmonary edema, and cardiogenic shock; the position of infarction; in-hospital complications; and history of myocardial infarction were assessed using medical records. Comorbidity was defined using an index based on the presence of eight conditions. RESULTS: Of 194 patients, 76 (39%) died in the first 6 months after myocardial infarction. In multiple logistic regression analyses, lack of emotional support was significantly associated with 6-month mortality (odds ratio, 2.9; 95% CI, 1.2 to 6.9) after controlling for severity of myocardial infarction, comorbidity, risk factors such as smoking and hypertension, and sociodemographic factors. CONCLUSIONS: When emotional support was assessed before myocardial infarction, it was independently related to risk for death in the subsequent 6 months.

Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study.

The 1-year follow-up data of a multicenter randomized controlled trial of methylprednisolone (30 mg/kg bolus and 5.4 mg/kg/hr for 23 hours) or naloxone (5.4 mg/kg bolus and 4.0 mg/kg/hr for 23 hours) treatment for acute spinal cord injury are reported and compared with placebo results. In patients treated with methylprednisolone within 8 hours of injury, increased recovery of neurological function was seen at 6 weeks and at 6 months and continued to be observed 1 year after injury. For motor function, this difference was statistically significant (p = 0.030), and was found in patients with total sensory and motor loss in the emergency room (p = 0.019) and in those with some preservation of motor and sensory function (p = 0.024). Naloxone-treated patients did not show significantly greater recovery. Patients treated after 8 hours of injury recovered less motor function if receiving methylprednisolone (p = 0.08) or naloxone (p = 0.10) as compared with those given placebo. Complication and mortality rates were similar in either group of treated patients as compared with the placebo group. The authors conclude that treatment with the study dose of methylprednisolone is indicated for acute spinal cord trauma, but only if it can be started within 8 hours of injury.

A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study.

Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain. We evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury. Methylprednisolone was given to 162 patients as a bolus of 30 mg per kilogram of body weight, followed by infusion at 5.4 mg per kilogram per hour for 23 hours. Naloxone was given to 154 patients as a bolus of 5.4 mg per kilogram, followed by infusion at 4.0 mg per kilogram per hour for 23 hours. Placebos were given to 171 patients by bolus and infusion. Motor and sensory functions were assessed by systematic neurological examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eight hours of their injury had significant improvement as compared with those given placebo in motor function (neurologic change scores of 16.0 and 11.2, respectively; P = 0.03) and sensation to pinprick (change scores of 11.4 and 6.6; P = 0.02) and touch (change scores, 8.9 and 4.3; P = 0.03). Benefit from methylprednisolone was seen in patients whose injuries were initially evaluated as neurologically complete, as well as in those believed to have incomplete lesions. The patients treated with naloxone, or with methylprednisolone more than eight hours after their injury, did not differ in their neurologic outcomes from those given placebo. Mortality and major morbidity were similar in all three groups. We conclude that in patients with acute spinal-cord injury, treatment with methylprednisolone in the dose used in this study improves neurologic recovery when the medication is given in the first eight hours. We also conclude that treatment with naloxone in the dose used in this study does not improve neurologic recovery after acute spinal-cord injury.

Association of cocaine use with sperm concentration, motility, and morphology.

Use of cocaine within 2 years of their first semen analysis has been found to be twice as common among men with sperm counts less than 20 X 10(6) mL (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.0, 4.6). Duration of cocaine use for five or more years was more common in men with low sperm motility (OR = 2.0, 95% CI 1.0, 4.1) and in those with low concentrations and a large proportion of abnormal forms. Other major risk factors for these three indicators of male subfertility also have been identified, but the cocaine risk factors remained after adjustment for them. This association, together with the high prevalence of cocaine use in the general male population, suggests cocaine may now be related to male subfertility and that history of use should be ascertained during diagnostic interviews.