Avorn J. The effect of cranberry juice on the presence of bacteria and white blood cells in the urine of elderly women. What is the role of bacterial adhesion? Advances in Experimental Medicine & Biology. 1996;408:185-6, .
Boyle P. Maisonneuve P. Bueno de Mesquita B. Ghadirian P. Howe GR. Zatonski W. Baghurst P. Moerman CJ. Simard A. Miller AB. Przewoniak K. McMichael AJ. Hsieh CC. Walker AM. Cigarette smoking and pancreas cancer: a case control study of the search programme of the IARC. International Journal of Cancer. 1996;67(1):63-71.
Boyle P. Walker AM. Alexander FE. Methods for investigating localized clustering of disease. Historical aspects of leukaemia clusters. IARC Scientific Publications. 1996;(135):1-20.
Gurwitz JH. Everitt DE. Monane M. Glynn RJ. Choodnovskiy I. Beaudet MP. Avorn J. The impact of ibuprofen on the efficacy of antihypertensive treatment with hydrochlorothiazide in elderly persons. Journals of Gerontology. Series A, 1996;51(2):M74-9.
Harari D. Gurwitz JH. Avorn J. Bohn R. Minaker KL. Bowel habit in relation to age and gender. Findings from the National Health Interview Survey and clinical implications. Archives of Internal Medicine. 1996,156(3):315-20.
Hayashi K. Walker AM. Japanese and American reports of randomized trials: differences in the reporting of adverse effects. Controlled Clinical Trials 1996;7(2):99-110.
Lanes SF. Sulsky S. Walker AM. Isen J. Grier CE 3rd. Lewis BE. Dreyer NA. A cost density analysis of benign prostatic hyperplasia. Clinical Therapeutics 1996;18(5):993-1004.
Monane M. Avorn J. Medications and falls. Causation, correlation, and prevention.Clinics in Geriatric Medicine. 1996;12(4):847-58.
Monane M. Bohn RL. Gurwitz JH. Glynn RJ. Levin R. Avorn. Compliance with antihypertensive therapy among elderly Medicaid enrollees: the roles of age, gender, and race. American Journal of Public Health. 1996;86(12):1805-8.
Monane M. Glynn RJ. Avorn J. The impact of sedative-hypnotic use on sleep symptoms in elderly nursing home residents. Clinical Pharmacology & Therapeutics. 1996;59(1):83-92.
Monane M. Kanter DS. Glynn RJ. Avorn J. Variability in length of hospitalization for stroke. The role of managed care in an elderly population. Archives of Neurology. 1996;53(9):875-80.
Oliveria SA. Felson DT. Klein RA. Reed JI. Walker AM. Estrogen replacement therapy and the development of osteoarthritis. Epidemiology 1996;7(4):415-9.
Rayon P, Serrano-Castro MA, Del Barrio H, Alvarez C, Montero D, Madurga M, Palop R, De Abajo FJ.: Hypnotic drug use in spain: A cross-sectional study based on a network of community pharmcies. Ann Pharmacother 1996;30:1092-1100.
Walker AM. Confounding by indication [editorial]. Epidemiology 1996;7(4):335-6.
Walker AM. Johnson ES. Bias in case-control studies of calcium antagonists [letter]. American Journal of Cardiology. 1996;78(3):380.
Walker AM. Stampfer MJ. Observational studies of drug safety. Lancet
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Abstract
We sought to identify differences in the description of adverse drug
experiences in reports of randomized clinical trials (RCTs) from the United
States and Japan, using diclofenac and simvastatin as test drugs. Reports
were identified in Medline (Index Medicus 1966-1990), EMBASE (Excerpta
Medica 1974-1990), JAPICDOC (1979-1990), and JOIS-III (JMEDICINE 1980-1990).
In each search keywords describing study design were paired with the drugs'
generic names, chemical names, and development numbers. Twenty-seven U.S.
reports (18 for diclofenac and 9 for simvastatin) and 22 Japanese reports
(17 for diclofenac and 5 for simvastatin) identified in these four databases
were selected for review. For each paper we identified the relation of
the article to the data (preliminary, primary, and secondary reports, reviews),
the means of identifying adverse reactions, the principal outcomes of the
trials, and a variety of descriptive measures relating to study design,
authorship, and elements of presentation. With few exceptions, Japanese
reports were not indexed in English-language databases, and studies from
the United States were not carried out in the Japanese databases. The Japanese
literature consisted exclusively of primary reports of clinical trials,
whereas the U.S. literature was dominated by review articles and secondary
reports of data from trials not fully published elsewhere. Japanese reports
contained more detail on adverse experiences but reported principally those
attributed to the drugs by attending clinicians. U.S. reports by contrast
offered little detail but tended to include all adverse experiences, whether
or not clinically attributed to drugs. A preponderance of U.S. articles
reported significant differences between drugs in safety or treatment efficacy,
whereas only one third of the Japanese articles did so for the same agents.
Reports from both countries offered few details of the methods used to
gather information on adverse drug experiences, and as a result the reported
absolute frequencies of such events are difficult to compare between trials
or to generalize to other settings. In conclusion, the reporting of adverse
reactions in clinical trials is inadequate in both the United States and
Japanese literature. The shortcomings are complementary in that reports
of U.S. trials contain insufficient detail and Japanese reports do not
interpret or synthesize experience. Clinical research into drug safety
in both countries could be improved through the adoption of simple standards
of clarity and consistency in the monitoring and reporting of drug adverse
effects.
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Abstract
Recent studies have indicated that estrogen users have a lower than
expected rate of concurrent osteoarthritis. We assessed the association
between estrogen replacement therapy and incident symptomatic osteoarthritis,
using a nested case-control design. We identified all incident cases of
hand, hip, and knee osteoarthritis in women members of the Fallon Community
Health Plan, age 20-89 years, from January 1, 1990, to December 31, 1993.
For each case, we selected a control woman matched by closest date of birth.
We used pharmacy records to classify women as new users, past users, ongoing
users (past and new users), and never-users of estrogen replacement therapy.
There were 60 informative case-control pairs. After controlling for obesity
and health care utilization, we found that new use of estrogen replacement
therapy was a predictor of new osteoarthritis diagnosis. Past use was inversely
associated with risk of osteoarthritis [adjusted odds ratio = 0.7; 95%
confidence interval (CI) = 0.3-1.9]. For ongoing use of estrogen replacement
therapy and osteoarthritis, the adjusted odds ratio was 1.4 (95% CI = 0.6-3.3).
The associations between osteoarthritis and both new use of estrogen replacement
therapy and utilization of services suggest that frequent medical care
increases the likelihood of diagnosis of osteoarthritis.
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Abstract
A multi-centre case-control study of pancreas cancer, designed to be
population-based, to use a random sample of local populations as controls
and to use a common protocol and core questionnaire, was conducted as the
first study of the SEARCH programme of the International Agency for Research
on Cancer. "Ever-smokers" were found to be at increased risk for pancreas
cancer compared with "never-smokers" consistently in all strata of gender,
response status and centre. Risk of pancreas cancer was found to increase
with increasing lifetime consumption of cigarettes, the relative risk rising
to 2.70 (95% C.I. 1.95 to 3.74) in the highest intake category. The overall
trend in risk was highly significant and the association was found consistently
in each stratum of gender, response status and centre. Fifteen years had
to pass from quitting cigarette smoking until the risk fell to a level
compatible with that in never-smokers among the heaviest group of smokers;
among the 2 lowest tertiles this happened within 5 years. Further, reported
smoking habits more than 15 years before diagnosis appeared to have no
influence on pancreas-cancer risk, irrespective of amount smoked. The results
are consistent with a causal role for cigarette smoking in the aetiology
of pancreas cancer and illustrate that ceasing to smoke cigarettes can
lead to reductions in the elevated risk of pancreas cancer produced by
this habit.
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Abstract
We assessed the frequency and cost of care for benign prostatic hyperplasia
(BPH) among approximately 165,000 subscribers to Fallon Community Health
Plan (FCHP), a group model health maintenance organization located in central
Massachusetts. We computed rates of episodes of medical services for BPH
using automated utilization files, and we estimated costs using Medicare
reimbursement schedules and medication average wholesale prices. We identified
3919 men who visited a physician for BPH from January 1, 1991, until December
31, 1994, during which time they contributed 8336 person-years to the analysis.
This population comprises approximately 12% of men at least 40 years old
at FCHP. From 1991 to 1994, 696 (18%) men received terazosin, 219 (6%)
men underwent a prostatectomy, and 41 (1%) men received finasteride. Men
averaged 1.66 office visits per year to a physician for BPH. Most office
visits (61%) were to a primary care physician, with 39% of the visits to
a urologist. Among patients who received terazosin, the frequency of office
visits increased slightly after receiving terazosin, from 2.14 to 2.62
visits per year. Among surgery patients, the frequency of visits declined
after prostatectomy, from 6.31 visits per year to 1.67 visits. The individual
annual cost rate for BPH care ranged from $25.00 to $25,352.00, with an
average of $364.00 per person and a median cost of $126.00. The major components
of the overall costs were hospital admissions (35%),terazosin dispensings
(29%), and physician office visits (19%), with outpatient hospital care
and ambulatory procedures accounting for the remaining 17%. Among men receiving
terazosin, the average cost was $1190.00 per person-year, and among patients
undergoing prostatectomy, the cost was $2630.00 per person-year. The prostatectomy
rate declined by nearly 80% during the study period, while the dispensing
rate for terazosin doubled, resulting in an overall decline in the total
cost of care for BPH from 1991 to 1994.
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Abstract
OBJECTIVES: This study measured compliance and related demographic
factors in a retrospective cohort of 4068 elderly outpatients newly starting
antihypertensive therapy from 1982 through 1988.
METHODS: Logistic regression modeling of data from the New Jersey Medicaid
program was used.
RESULTS: These patients filled antihypertensive prescriptions covering
an average of only 179 days in the 365-day follow-up period (49%) Good
compliance (> or = 80%) was associated with advanced age (odds ratio [OR]
= 2.12, for patients 85 or older) and White race (OR = 0.55 for Blacks).
There was no relationship between compliance and gender.
CONCLUSIONS: Despite the efficacy of antihypertensive therapy in preventing
cardiovascular morbidity, such high rates of noncompliance may contribute
to suboptimal patient outcomes.
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Abstract
Both medication use and fall rates increase with advancing age. The
increased risk of falls conferred by drugs is clearest for psychoactive
agents such as long-acting benzodiazepines. The most frail patients (those
likeliest to fall) also are receiving the largest drug burden, imposing
considerable confounding by indication. Nonetheless, improving the drug
regimen is probably one of the most effective means of reducing fall risk,
especially in the frail elderly.
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Abstract
OBJECTIVES: To measure hospital stay for acute stroke care and to describe
health services and demographic factors associated with longer length of
stay (LOS).
DESIGN: Observational, retrospective consecutive case series.
SETTING: Large tertiary-care teaching hospital in Massachusetts.
PATIENTS: The patient population comprised 745 patients aged 65 years
and older admitted with ischemic stroke from 1982 through 1995.
MAIN OUTCOME MEASURES: Hospital LOS (1-5, 6-10, and >10 days) as well
as total charges and discharge location.
RESULTS: Median LOS was 7 days (range, 1-289 days), and median total
charges were $8740 (range, $522-$135172); LOS explained 62% of the variance
in total charges. Insurance status was a major factor in determining LOS:
after possible confounders were controlled for, patients enrolled in a
health maintenance organization were significantly less likely to have
long hospital stays (odds ratio [OR], 0.45; 95% confidence interval, 0.31-0.66)
than were conventional Medicare enrollees, while the LOS of patients with
other insurance coverage was no different from that of Medicare patients.
Longer LOS was significantly associated with greater comorbidity (OR, 1.52
for a Charlson comorbidity index >2), institutionalization prior to hospital
admission (OR, 1.83), and unmarried status (OR, 1.37) and was inversely
associated with year of admission (OR, 0.30 in years 1991-1995 vs 1982-1986).
Age, sex, and race were not associated with LOS. Discharge to a nursing
home or inpatient rehabilitation site was not associated with type of insurance
coverage (OR, 1.10; 95% confidence interval, 0.72-1.69 for patients in
a health maintenance organization vs conventional Medicare patients).
CONCLUSIONS: There is marked variability in length of hospital stay
for ischemic stroke among the elderly, even after underlying patient differences
are controlled for. Managed care may result in increased efficiency of
in-hospital care and improved discharge planning for these patients; further
study of the ultimate clinical outcomes of such care is needed.
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Abstract
BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) may alter
blood pressure through their inhibitory effects on prostaglandin biosynthesis.
Such potential hypertensive effects of NSAIDs have not been adequately
examined in the elderly, who are the largest group of NSAID users.
METHODS: We performed a randomized, double-blind, two-period crossover
trial of ibuprofen (1800 mg per day) vs placebo treatment in patients older
than 60 years of age with hypertension controlled with hydrochlorothiazide.
While continuing their usual thiazide dosage, subjects were randomized
to a 4-week treatment period (ibuprofen or placebo) followed by a 2-week
placebo wash-out period and a second 4-week treatment period with the alternative
therapy. Supine and standing systolic and diastolic blood pressures were
measured weekly.
RESULTS: Of 25 randomized subjects, 22 completed the study protocol
(mean age = 73 +/- 6.7 years). Supine systolic blood pressure and standing
systolic blood pressure were increased significantly with ibuprofen treatment,
compared with placebo. Mean supine systolic blood pressures were 143.8
+/- 21.0 and 139.6 +/- 15.9 mmHg on ibuprofen and placebo, respectively
(p = .004). Mean standing systolic blood pressures were 148.1 +/- 19.9
and 143.4 +/- 17.9 mmHg on ibuprofen and placebo, respectively (p = .002).
CONCLUSION: We conclude that 1800 mg per day of ibuprofen does induce
a significant increase in systolic blood pressure in older hypertensive
patients treated with hydrochlorothiazide. NSAID therapy may negatively
impact the control of hypertension in elderly patients.
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Abstract
BACKGROUND: Constipation is widely considered to be a common problem
among the elderly, as evidenced by the high rate of laxative use in this
population. Yet, age-related prevalence studies of constipation generally
do not distinguish between actual alteration in bowel movement frequency
and subjective self-report of constipation.
OBJECTIVE: To determine the relationship between advancing age and
bowel habit.
METHODS: We employed data collected on 42,375 subjects who participated
in the National Health Interview Survey on Digestive Disorders based on
interviews with a random nationwide sample of US households. We examined
the following characteristics reported by this population according to
selected age groupings by decade: constipation, levels of laxative use,
and two bowel movements per week or less.
RESULTS: Contrary to conventional wisdom, there was no age-related
increase in the proportion of subjects reporting infrequent bowel movements.
Nonetheless, the prevalence of self-report of constipation increased with
advancing age, with a greater proportion of women reporting this symptom
than men across all age groups. Laxative use also increased substantially
with aging; while women were more likely to use laxatives than men, this
effect attenuated with advancing age. A U-shaped relationship was observed
between advancing age and bowel habit in men and women; 5.9% of individuals
younger than 40 years reported two bowel movements per week or less compared
with 3.8% of those aged 60 to 69 years and 6.3% of those aged 80 years
or older. This relationship persisted after adjusting for laxative use.
CONCLUSION: These findings suggest that a decline in bowel movement
frequency is not an invariable concomitant of aging. In elderly patients
who report being constipated, it is essential to take a careful physical,
psychological, and bowel history rather than to automatically assume the
need for laxative use.
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Abstract
OBJECTIVE: To determine the frequency of sleep-related complaints among
institutionalized elderly subjects and to assess the relationship between
perceived sleep quality and the use of sedative-hypnotic agents and other
psychoactive medications.
METHODS: In 12 nursing homes in Massachusetts, we conducted observational,
cross-sectional, and longitudinal studies of 145 institutionalized elderly
subjects (average age, 83.0 years; age range, 65 to 105 years). We recorded
the patients' demographic characteristics and all medication use (both
scheduled and as needed) during a 1-month baseline period. A research assistant
who was blinded to diagnoses and medication use performed detailed neuropsychologic
testing and administered a series of standardized questions concerning
difficulty sleeping, early morning awakening, and time spent awake in bed.
Medication use and patient assessments were repeated after a 6-month interval.
RESULTS: One or more sleep-related complaints were present at baseline
in 94 (65%) of the residents studied. Using logistic regression to adjust
for potential confounding, we found no relationship in the baseline month
between use of sedative-hypnotic agents and the presence or absence of
sleep complaints. After 6 months of follow-up, 27 (19%) of the residents
had decreased their use of sedative-hypnotic agents and 23 (16%) had increased
their use. However, there was no relationship between decreased use of
sedative-hypnotic agents and worsened sleep (p > 0.20) or between their
increased use and improved sleep reports (p > 0.10). Improvement in functional
status was significantly associated with improved sleep at follow-up (p
< 0.005).
CONCLUSIONS: Sleep complaints occur in the majority of institutionalized
elderly persons. Neither cross-sectional nor longitudinal analyses showed
a relationship between patterns of sedative-hypnotic use and the presence,
absence, or change in sleep complaints.
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Abstract
Objective: To investigate how hypnotic drugs are used in Spain, specifically,
(1) to characterize the user population in some simple demographic (e.g.
sex, age) and clinical (e.g. type of insomnia, type of physician who prescribed
the drug) variables; (2) to estimate the proportion of long-term users
(>3 mo); (3) to determine the frequency of different administration schedules;
(4) to determine whether the kind of hypnotic drug prescribed according
to the duration of its effect correlates with the type of sleep disorder
or patient age, and (5) to compare the dosage used by the elderly with
that used by adults.
Design: Cross-sectional pharmacy-based study.
Setting: A network of 318 community pharmacies throughout Spain.
Subjects: Patients (n=5324) requesting a hypnotic drug for insomnia
who agreed to take part in the study.
Main outcome measures: Distribution of the use of hypnotic drugs by
age, sex, type of insomnia, type of physician, specific hypnotic drug,
daily dosage, treatment schedule, and duration of treatment.
Results: Women (67%) and the elderly (58%) constituted the largest
subgroups in the sample. Difficulties in sleep onset and in sleep maintenance
as single disorders were reported by 38% and 37% of users, respectively.
Prescriptions were written by general practitioners in 80% of cases. Daily
use was reported by 88% and long-term use (>3 mo) by 72% of the users.
Long-term treatment was two to threefold more frequent in the elderly than
in the middle-aged subjects. Intermediate-action hypnotic drugs were used
by 59% of subjects, short-action drugs by 24%, and long-action drugs by
17%. The type of hypnotic drug prescribed was not related to the kind of
sleep disorder or the age of patients. Specialists prescribed long-action
hypnotic drugs more often than did general practitioners. No relevant differences
were observed between dosages used by the elderly and those used by adults.
In both groups the dosage taken by most patient, regardless of the drug,
corresponded to the available strength. Substitution drugs for triazolam
belonged to the intermediate-action class in 53% of the cases.
Conclusions: Recommendations on hypnotic drug use are largely not followed
in Spain. Most patients are taking hypnotic drugs daily, over long time
periods, and without an adequate dosage titration according to age. Measures
should be taken to correct this situation.
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