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Tips from Other Journals
Different Fat-Restricted Diets and Effect on Lipid Levels
Since dietary modification is an initial step in the management of hypercholesterolemia, it seems logical to assume that greater fat restriction may lead to larger decreases in low-density lipoprotein (LDL) cholesterol levels. Knopp and colleagues conducted a randomized comparison trial of four different low-fat diets to determine the effects of varying degrees of fat restriction on lipid levels.
A total of 444 men were recruited from an industrial firm for the one-year study. Each participant had two LDL determinations greater than the 75th percentile (for age). Subjects with triglyceride levels below the 75th age-specific percentile were classified as having hypercholesterolemia and those with triglyceride levels above the 75th age-specific percentile were classified as having combined hyperlipidemia. Men were excluded from the study if they had medical conditions that might cause hyperlipidemia, such as diabetes mellitus, nephrotic syndrome or hypothyroidism, or if they were receiving medications that might affect lipid levels, such as beta-adrenergic blockers, thiazide diuretics and lipid-lowering drugs.
Four fat-restricted diets were studied: 30 percent fat and 300 mg per day of cholesterol; 26 percent fat and 200 mg per day of cholesterol; 22 percent fat and 100 mg per day of cholesterol; and 18 percent fat and 100 mg per day of cholesterol. Men with combined hyperlipidemia were not assigned to the diet containing 18 percent fat. Study subjects received training on following the fat-restricted diets. A four-day food diary was collected at baseline and at five other times during the study. The average baseline fat intake was 34 to 36 percent. Lipoprotein analysis was performed at one, three, six, nine and 12 months.
The men on the lowest-fat diets did not lose significantly more weight than those on the less-restrictive diets. Men in the 30 percent fat intake group actually ingested a diet containing only 27 to 28 percent fat. The group adhering to the 26 percent fat diet met their goal intake. The men assigned to diets containing 22 and 18 percent fat did not meet their goals, ingesting 25 and 22 percent fat, respectively.
LDL levels were reduced significantly in all of the study groups. In the hypercholesterolemic men, LDL levels fell by 5.3, 13.4, 8.4 and 13.0 percent on the 30, 26, 22 and 18 percent fat diets, respectively. However, high-density lipoprotein (HDL) cholesterol levels decreased 2.8 percent and 3.2 percent in the hypercholesterolemic men consuming the two most restrictive diets. Plasma triglyceride levels increased by 22 percent and 39 percent in the hypercholesterolemic men on the two most fat-restrictive diets.
In the combined hyperlipidemia group, the decrease in LDL levels was not as great as that in the hypercholesterolemic group. LDL levels dropped 7.0, 2.8 and 4.6 percent with the three different diets these men followed. Triglyceride levels did not increase in the men with combined hyperlipidemia who were assigned to the most restrictive diet.
The authors conclude that long-term moderate restriction of fat intake (both total and saturated fat) is effective in reducing LDL levels. More aggressive fat restriction offers little further advantage and may have undesirable effects in patients with hypercholesterolemia.
GRACE BROOK HUFFMAN, M.D.
Knopp RH, et al. Long-term cholesterol-lowering effects of 4 fat-restricted diets in hypercholesterolemic and combined hyperlipidemic men: the dietary alternatives study. JAMA 1997 November;278:1509-15.
Outcomes of Infants Born at 24 to 26 Weeks of Gestation
Data on morbidity and mortality of very premature infants are largely based on studies conducted before the extensive use of steroids and surfactant, and other innovations that have significantly improved the prognosis of these infants. Kilpatrick and colleagues reviewed data on infants born at 24 to 26 weeks of gestation to assess rates of mortality and morbidity in these infants.
The authors identified 138 infants born between 1990 and 1994 from obstetric records and used early examination or ultrasonic estimation as measures of gestational age. Patients who underwent termination of pregnancy or had intrauterine fetal demise were excluded from the study. Infants with severe congenital anomalies were also excluded from the estimations of mortality and morbidity. During the study period, antenatal steroids were used routinely, and surfactant was given to all infants born before 27 weeks of gestation.
Spontaneous preterm labor was the cause of delivery in 54 of the 138 infants (39 percent). In the remaining cases, premature birth was attributed to premature rupture of membranes, preeclampsia, abruption or placenta previa. Seven infants were stillborn and three of those born at 24 weeks of gestation were not resuscitated. Eighteen of the infants born at 24 weeks (43 percent), 31 of those born at 25 weeks (74 percent) and 45 infants born at 26 weeks (83 percent) survived.
One third of the infants born at 24 weeks of gestation had severe retinopathy or chronic lung disease, but this incidence decreased by about one half for every additional week gained in utero. Only two of the infants born at 26 weeks of gestation had severe retinopathy, and three had chronic lung disease. The mean duration of hospital stay for infants born at 24 weeks of gestation was 4.0 months, compared with 2.9 months for the infants born at 25 weeks of gestation and 2.7 months for infants born at 26 weeks of gestation. The cost per survivor was calculated to be $294,749 for infants born at 24 weeks of gestation, $181,062 for those born at 25 weeks and $166,215 for those born at 26 weeks.
In a related article, Piecuch and colleagues report on the one-year follow-up of 86 infants born at 24, 25 or 26 weeks of gestation. The incidence of cerebral palsy was similar in all three groups: two of 18 infants born at 24 weeks of gestation (11 percent), six of 30 infants who were born at 25 weeks (20 percent) and four of 38 infants who were born at 26 weeks (11 percent).
Cognitive development was strongly related to gestational age. Five of the infants born at 24 weeks of gestation (28 percent) had normal cognitive development. Fourteen of the infants born at 25 weeks (47 percent) and 27 of the infants born at 26 weeks (71 percent) had normal cognitive development. Cognitive outcome showed a significant relationship with four risk factors: chronic lung disease, intracranial hemorrhage or periventricular leukomalacia, substance abuse and high social risk.
The percentage of infants who were neurologically normal also was related to gestational age. Twelve of the infants born at 24 weeks (67 percent) demonstrated normal neurologic outcome, compared with 22 of the infants born at 25 weeks (73 percent) and 34 of the infants born at 26 weeks (89 percent). Poor neurologic outcome correlated with grade 3 or grade 4 intracranial hemorrhage or periventricular leukomalacia. It did not correlate with chronic lung disease, sex of the infant, substance abuse or high social risk.
The authors calculate that the chances of an infant having normal or borderline-normal cognitive outcome is 26 percent in those born at 24 weeks of gestation, 52 percent at 25 weeks and 74 percent at 26 weeks.
ANNE D. WALLING, M.D.
Kilpatrick SJ, et al. Outcome of infants born at 24-26 weeks' gestation: I. survival and cost. Obstet Gynecol 1997;90:803-8. Piecuch RE, et al. Outcome of infants born at 24-26 weeks' gestation: II. neurodevelopmental outcome. Obstet Gynecol 1997 November;90:809-14.
Effects of Diphenhydramine and Loratadine on Sedation
First-generation histamine receptor antagonists such as diphenhydramine are known to cause central nervous system depressant effects. Decrements in cognitive and psychomotor performance after administration of antihistamines are generally attributed to increased sedative effects. Second-generation histamine-receptor antagonists such as loratadine are considered less sedating. Kay and associates conducted a study to assess drug effects on sedation, mood, cognition and psychomotor functioning.
Ninety-eight healthy patients were randomly assigned to receive loratadine (in a single dose of 10 mg), diphenhydramine (in a single dose of 50 mg, followed by two doses of 25 mg and one placebo tablet on day one, and then four daily doses of 25 mg), or one placebo tablet four times daily. Patients were tested before treatment, on day one after administration of medication or placebo, and on days three and five of the study. After the initial dose of diphenhydramine, patients demonstrated poorer cognitive performance than those taking loratadine or placebo on measures of divided attention, working memory and vigilance. Patients taking diphenhydramine reported more sleepiness and fatigue than patients taking loratadine. Following administration of diphenhydramine, patients also demonstrated lower levels of motivation and rated the quality of test performance as lower than did those receiving loratadine. On days three and five of the study, patients who received diphenhydramine did not perform as well on a test of tracking errors (reflecting lapses of attention) as those who received placebo. Adverse events were minor in all study groups and did not preclude completion of the study. Results of this study demonstrated differences in psychomotor performance, mood and sedation between groups taking diphenhydramine and groups taking loratadine. Drug effects were principally limited to initial dosing; however, on day three, after the dosage of diphenhydramine had been lowered, patients continued to report central nervous system depressant effects on mood and sedation. These patients also continued to make significantly more tracking errors. Results for loratadine were comparable with results for placebo. Loratadine had no more effect on mood or sedation than placebo. Cognitive and psychomotor test findings demonstrated no differences when loratadine or placebo was administered.
The authors conclude that decrements in performance associated with diphenhydramine therapy extend beyond the well-established hazards associated with driving and operating heavy machinery. The tasks selected for this study were chosen specifically to mimic the demands of the modern workplace. The findings demonstrate that sedating antihistamines may increase the risk of error, particularly when psychomotor tasks are performed under divided attention. Furthermore, the decrease in motivation and quality of performance may translate into decreased productivity for workers and students.
BARBARA APGAR, M.D.
Kay GG, et al. Initial and steady-state effects of diphenhydramine and loratadine on sedation, cognition, mood, and psychomotor performance. Arch Intern Med 1997 November 10;157:2350-6.
Alcohol Use and Mortality Rates from Various Causes
Compared with persons who abstain from drinking alcohol, persons who use alcohol regularly have higher death rates from suicide, certain cancers and cirrhosis. However, data also show that people who drink alcohol have lower rates of death from thrombotic stroke and ischemic heart disease. The reasons for this latter association are not clear. Thun and associates, as part of the Cancer Prevention Study II of the American Cancer Society, assessed the relationship between death rates from various causes and alcohol consumption in American adults.
Data were compiled for approximately 490,000 persons aged 30 years and older (mean age: 56 years). The study subjects were among the 1.2 million participants in the Cancer Prevention Study II, a prospective study that began in 1982. A four-page questionnaire was used to obtain information about alcohol and tobacco use, diet and other factors that may have a bearing on mortality. Alcohol consumption was quantified into five categories ranging from none to more than four drinks a day. The majority of participants were married, college graduates, middle-class and white.
An increase in the percentage of people who smoked paralleled an increase in alcohol consumption. Only 22 percent of the study subjects who had less than one drink per day were smokers, compared with 37 percent of those who had four or more drinks a day.
By 1991, a total of 46,000 deaths had occurred among the 490,000 participants. Alcohol consumption was associated with increased rates of death from cirrhosis, alcoholism and cancers of the mouth, esophagus, pharynx, larynx and liver combined. The rates of death were three to seven times higher among people who reported consuming four or more drinks a day. The mortality rate from external causes, such as suicide and accidents, was increased in men who consumed four or more drinks a day. The mortality rate from breast cancer was 30 percent higher in women who had at least one drink a day compared with women who did not drink alcohol.
With respect to death from cardiovascular disease, alcohol consumption was associated with a decreased mortality rate. Compared with abstainers, men and women who reported consuming at least one drink a day had a 30 to 40 percent lower mortality rate from all cardiovascular diseases combined. The rates of death from all causes were lowest among men and women who reported ingesting one alcoholic drink daily and were about 20 percent below those of nondrinkers. The risk of death from cardiovascular disease in smokers between 35 and 69 years of age was double that of nonsmokers.
The authors draw several conclusions from this study. First, persons who consume one or two drinks daily have a lower overall mortality rate than nondrinkers. Second, balancing the adverse effects of drinking with any beneficial effects on mortality depends on the amount of alcohol consumed as well as the person's age and risk of cardiac disease. Finally, alcohol consumption does not compensate for the significant increase in the risk of cardiovascular disease and death from cigarette smoking.
JEFFREY T. KIRCHNER, D.O.
Thun MJ, et al. Alcohol consumption and mortality among middle-aged and elderly U.S. adults. N Engl J Med December 1997;337:2705-14.
Shunt as an Effective Alternative for Esophageal Varices
Treatment options for acute or recurrent hemorrhage secondary to esophageal varices now include the transjugular intrahepatic portosystemic shunt (TIPS) procedure. TIPS provides physicians with a treatment option other than surgery during acute bleeding episodes. Sahagun and associates observed 100 consecutive patients who had TIPS performed for acute or recurrent esophageal variceal hemorrhage, and who were refractory to medical management and had advanced liver disease.
Patients were studied prospectively after the TIPS procedure to evaluate recurrent hemorrhages, survival rates, indicators for hepatic decompensation, short- and long-term shunt patency and complications.
Study results showed that the procedure did reduce portal pressures. Ten complications, including pulmonary edema, hepatic arterial injury and sepsis, and one death associated with the procedure were reported. The cumulative survival rate was 85 percent at 30 days, 71 percent at one year and 54 percent at two years. Recurrent hemorrhage occurred in 20 percent of patients at one year and in 25 percent at two years. Clinical parameters demonstrated an improvement in the patients with ascites, but hepatic encephalopathy also increased. Forty-seven percent of the patients needed intervention during the study to maintain shunt patency.
The authors conclude that TIPS provides an alternative procedure in patients with acute or recurrent esophageal varices and avoids the risks associated with surgical intervention. If performed appropriately, TIPS can reduce the risk of hemorrhage from varices while having no impact on the patient's eligibility for liver transplant.
KARL MILLER, M.D.
Sahagun G, et al. Outcome of 100 patients after transjugular intrahepatic portosystemic shunt for variceal hemorrhage. Am J Gastroenterol 1997 September;92:1444-52.
Adverse Events and Age at Second MMR Vaccination
Recommendations for the timing of a second dose of measles-mumps-rubella vaccine (MMR2) differ. The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommends that MMR2 be given between four and five years of age (before school entry, an age when access to the children by the physician is presumably greater). In contrast, the American Academy of Pediatrics recommends that the second dose be given between 11 and 12 years of age, when multiple guidance issues should be discussed and other vaccinations may be needed. Davis and associates analyzed data on clinical events following administration of MMR2 in these two age groups to compare any differences in the rate of adverse reactions.
Data were gathered from two health maintenance organizations (HMOs) that were members of the CDC Vaccine Safety Datalink study. MMR2 was routinely administered between four and six years of age at one HMO, and at the other, it was given between 10 and 12 years of age.
To be included in the analysis, children were required to have been enrolled in the HMO for at least three months before and three months after vaccination. Clinical events in the 30-day period after immunization were compared with those in a 30-day period before immunization to account for age-related differences in health care use. Visits to health care professionals within 30 days after vaccination were reviewed and information was collected on potential vaccine-related adverse events such as rash, fever, malaise, injection-site induration, seizures, neurologic and musculoskeletal symptoms, lymphadenopathy, thrombocytopenia, aseptic meningitis and joint pain.
MMR2 was received by 8,514 children between four and six years of age; 523 of these children were seen in the 30 days after immunization. Of these, 31 had symptoms potentially related to vaccination. A total of 18,036 patients received MMR2 between 10 and 12 years of age; 2,907 of these children were seen in the month after immunization. Sixty-eight of these children had symptoms potentially related to vaccination.
Compared with younger children, children who were 10 to 12 years old at the time of MMR2 administration were more likely to have health care visits for rash, seizures and joint pain (odds ratio: 1.78). The younger children had significantly fewer visits after the immunization (odds ratio: 0.52). Older girls were significantly more likely than older boys to develop joint pain and rash after immunization with MMR2 (odds ratio: 1.83 in girls versus 1.23 in boys).
The authors conclude that there are valid reasons for administering MMR2 between four and six years of age or between 10 and 12 years of age. The findings of their study suggest that the risk for adverse reactions is greater in children who receive MMR2 at an older age. As a limitation of their study, they note that it probably underestimated the true rate of clinical events following MMR2 immunization. Many children with mild symptoms following immunization do not seek medical care, and these children would have been missed in the authors' study. They also note that it is possible that the 10- to 12-year-old children may have been more likely than the younger children to seek medical care after MMR2 immunization.
GRACE BROOK HUFFMAN, M.D.
Davis RL, et al. MMR2 immunization at 4 to 5 years and 10 to 12 years of age: a comparison of adverse clinical events after immunization in the Vaccine Safety Datalink Project. Pediatrics 1997 November;100:767-71.
Use of Compression for Venous Leg Ulcers
Venous leg ulcers are common recurrent conditions, but uncertainty regarding the optimal management of the condition remains. Most treatments are based on local compression using bandaging or hosiery. Fletcher and colleagues conducted a research review to evaluate the effectiveness of the most common compression systems for the treatment of venous leg ulcers.
The authors searched 19 databases (including Medline) and also reviewed data contained in reference material, information provided by authors and manufacturers, and other sources for randomized, controlled trials assessing the effectiveness compression for treating venous leg ulcers. The trials identified were reviewed for inclusion in the study using strict criteria. Data from 24 relevant trials were pooled to provide study results.
Only six trials compared compression and noncompression treatments. Each of these trials involved small numbers of patients (from 30 to 69), and significantly increased healing rates using compression were reported in all but one study. The one exception was a study that showed a nonsignificant increase in healing rates with the use of compression. Net results showed a significantly higher proportion of ulcers healed when compression was used. The remaining studies compared different forms of compression. In spite of differences in the systems and methodology used, high-compression systems performed better than low-compression and single-layer systems. No clear differences could be identified in rates of healing using different compression systems such as boots, hosiery and multiple forms of bandaging. Two small studies that examined the effect of adding intermittent pneumatic compression stockings or Unna's boot found a net benefit in the overall odds of healing.
The authors conclude that any correctly applied compression system appears to improve the healing of uncomplicated venous ulcers. They also comment on the difficulties in standardizing research in this area, particularly the difficulty regarding staff who apply the same compression systems under different circumstances, resulting in widely differing pressures, making comparison difficult. They advise that physicians focus on ensuring that compression systems are used properly rather than focusing on the selection of the compression system itself. The authors call for more well-designed, large clinical trials to discern differences in efficacy and cost among the various compression systems.
ANNE D. WALLING, M.D.
Fletcher A, et al. A systematic review of compression treatment for venous leg ulcers. BMJ 1997 October; 315:576-80.
Seroprevalence of the Rubeola Antibody in Pregnant Women
Before widespread immunization, rubeola (measles) was the most communicable disease of childhood, and most women of reproductive age had high levels of immunity following natural infection. This resulted in a low incidence of rubeola during pregnancy (from 0.4 to 0.6 cases per 10,000 pregnancies). However, those women who contracted rubeola during pregnancy had high rates of premature labor, spontaneous abortion, maternal complications and even mortality as a result of disease. An increasing number of adult rubeola cases have recently been reported. In 1994, 48.8 percent of the rubeola cases reported occurred in persons from 15 to 39 years of age. Neubert and colleagues conducted a cross-sectional study to measure antibodies to the rubeola virus in women presenting for prenatal care to estimate the need for preventive measures such as postpartum vaccination.
Women included in the study presented for care at urban or suburban medical facilities, either resident-supervised clinics or private practices. Blood samples were collected from 768 women presenting between December 1992 and August 1994. The mean age of the women studied was 26.4 years, and the mean gravidity was 2.6. A seronegative result was defined as a hemagglutination test titer of 1:8 or less (i.e., Measelisa IgG value of 0.13 or less). Using these criteria, 75 women (9.8 percent) were seronegative. Women who were seronegative tended to be younger than those with immunity, but no significant relationship could be demonstrated between seronegativity and gravidity or parity.
The percentage of women who were nonimmune for rubeola was highest in those who described their race as "other" (13 percent), followed by white (12.4 percent) and black (4.3 percent). Women at the suburban sites were significantly more likely to be nonimmune than those who presented at the inner-city sites. The rate of seronegativity in suburban women attending the resident clinic was 20.5 percent, compared with 9.2 percent of the suburban private practice patients, 8.2 percent of inner-city patients seen in private practice settings and 3.2 percent of inner-city patients attending resident-supervised clinics. Many of the women who presented at the suburban resident-managed clinics were Hispanic and may have had decreased access to vaccination because of recent immigration or lack of contact with traditional public health services.
The authors conclude that an appreciable number of women presenting for prenatal care may lack antibodies to the rubeola virus. They attribute the low rates of seronegativity in inner-city women to public health campaigns targeting minority groups. The authors call for greater vigilance in ascertaining the rubeola immune status of women of childbearing age and the identification of patients who should receive the combined measles, mumps and rubella vaccine in the postpartum period.
ANNE D. WALLING, M.D.
Neubert AG, et al. The seroprevalence of the rubeola antibody in a prenatal screening program. Obstet Gynecol 1997 October;90:507-10.
EDITOR'S NOTE: The authors of this study are concerned about complacency deriving from the low incidence of rubeola currently reported in the United States. They found that overall, approximately 10 percent of pregnant women were vulnerable to measles, and in one subgroup, one fifth of all pregnant women were at risk. Measles is one of the most infectious diseases known, and outbreaks have occurred when only 3 to 7 percent of the population was at risk. The number of adults at risk for measles in the United States appears to be steadily increasing because immunization was either missed or was ineffective, and natural infection (which stimulates immunity) has been absent for many years. The measles epidemic scenario has already been played out in West Africa, where a measles epidemic disproportionately affected young adults, particularly pregnant women, with serious and often fatal results for mothers and neonates. Perhaps it is time for pilot studies to measure the prevalence of seronegativity to rubeola in representative U.S. adult populations. This information could contribute to rational strategies to prevent outbreaks of measles. Measles, particularly in adults, is not a benign disease. The stakes for prevention are now higher than they were before the introduction of childhood immunization: it would be tragic if the long-term consequences of immunization were to displace the impact of the disease to the adult and neonatal populations.
--A.D.W.
Evaluation of Patients with Transient Global Amnesia
Transient global amnesia involves the sudden loss of memory of recent events and a transient inability to retain new information. The incidence is higher in people 50 years of age and older, although it remains a rare occurrence. The patient with transient global amnesia may be disoriented, but behavior is otherwise normal. Most attacks resolve within several hours, although the patient remains amnestic to events that occurred during the episode. Brown conducted a literature review and presents criteria for emergency diagnosis of patients with transient global amnesia.
The following criteria should be used in the evaluation of a patient with transient global amnesia: an attack must be witnessed by an observer who can provide additional information; anterograde amnesia (inability to form new memories) must be present; no other cognitive impairment or loss of personal identity may be present; patients with transient global amnesia know their names and have had no recent history of head trauma or seizures in the past two years; focal neurologic signs and epileptic features are absent; and resolution of the attack should occur within 24 hours.
Most cases of transient global amnesia are preceded by an emotional stress, intense pain or cold, or strenuous physical activity. The specific cause is unknown. Patients may feel something is wrong but often have to be urged by a concerned observer to seek medical help. Most patients with transient global amnesia are disoriented to time and place and exhibit repetitive questioning that may last throughout the attack. Although patients are described as confused, they do not exhibit features of a true confusional state, can follow complex commands and do not confabulate.
When diagnostic criteria are properly applied, transient global amnesia is not difficult to diagnose because it is a unique entity. However, several disorders may be misdiagnosed as transient global amnesia. These include acute confusional states such as toxin-induced memory loss, psychogenic amnesia and transient complex partial seizures that present in the postictal state. Each of these, however, has distinct accompanying symptoms or physical findings.
Detailed work-ups are unproductive in patients who have all of the features of transient global amnesia unless other clinical indications are present. No evidence supports the use of toxicologic evaluations, metabolic and electrolyte testing, spinal tap with spinal fluid analysis, computed tomography of the head or electroencephalography unless the initial examination reveals an appropriate indication, such as focal neurologic deficits. If the diagnosis is in doubt, early neurologic consultation is appropriate. Family members and patients should be reassured that the attack will end within 24 hours. Patients whose attack has not yet ended should be closely followed.
There is no increased incidence of vascular deaths or epilepsy in patients with an episode of transient global amnesia, but a significantly greater proportion of persons with recurrent episodes of transient global amnesia go on to experience epilepsy than do control subjects. Patients with recurrent episodes might best be advised not to drive for 12 months. Stroke morbidity is not increased in patients with transient global amnesia, and the risk of a recurrent attack of transient global amnesia within five years ranges from 3 to 20 percent.
The authors conclude that transient global amnesia is a benign syndrome with a low risk of subsequent neurologic or vascular disease. Evaluations should be extensive only if focal neurologic signs accompany the presenting symptoms.
RICHARD SADOVSKY, M.D.
Brown J. ED evaluation of transient global amnesia. Ann Emerg Med 1997 October;30:522-6.
Prevalence of Depression in Healthy Elderly Persons
The prevalence of major depression in elderly people has been estimated to range from less than 3 percent to more than 12 percent of the population. Recent studies have suggested that there is an increased risk for depression in elderly patients. Roberts and associates investigated the effects of age on the prevalence of depression in patients 50 years of age and older to determine if aging is an independent risk factor for depression.
A total of 2,219 patients (mean age: 64.7 years) were included in the two-year study. Depression was measured using 12 diagnostic symptom criteria for a major depressive episode as outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R and DSM-IV). Basic information concerning both physical and emotional well-being was also collected for each patient. After adjusting for all other variables (i.e., sex, education, marital status, functional impairment, social support, etc.) the results demonstrated no increased incidence of depression with age in the two years studied.
The authors conclude that other age-related events increase the risk of depression in elderly patients, in particular chronic physical health problems and related disabilities. Healthy, normally functioning older adults, however, are at no greater risk for depression than younger adults and even adolescents. The authors stress that intervention strategies aimed at maintaining health and preventing impairment and disability may reduce the prevalence and impact of depression in older adults.
KARL MILLER, M.D.
Roberts RE, et al. Does growing old increase the risk for depression? Am J Psychiatry 1997 October;154:1384-90.
Cervical Score as a Predictor of Successful Labor Induction
Although the Bishop score, or some adaptation of this basic scoring system, is widely used to predict the outcome of induction of labor, it does not perform well clinically, and more accurate prognostic indicators would be useful. Williams and colleagues compared the accuracy of a cervical score based on cervical ripening with the classic Bishop score in predicting successful induction of labor and vaginal delivery.
The 443 women in the study had initial Bishop scores of less than nine at the time that delivery was required for obstetric or fetal indications. For the first six weeks of the study, scores assessed by the residents were confirmed by attending physicians until uniformity was obtained. Cervical dilation and length were estimated in centimeters. Patients in the study were stratified by gestational age, parity and initial Bishop score, and then randomly assigned to receive either hygroscopic cervical dilation or prostaglandin E2 for cervical ripening. The principal outcomes measured were the onset of active labor within 12 hours of placement of the cervical dilators or prostaglandin, and vaginal delivery.
The two groups of patients were similar with respect to Bishop scores and other measures of cervical status. They were also similar in maternal and pregnancy characteristics. After cervical ripening, the two groups did not differ in Bishop score, cervical consistency or cervical position.
Compared with the Bishop score, cervical dilation was a better predictor of successful labor induction, duration of the latent phase of labor, duration of the second stage, oxytocin use and successful vaginal delivery, both before and after cervical ripening. Successful labor induction was associated with lower maternal weight and body mass index, greater gestation and decreased nulliparity. Vaginal delivery was associated with lower maternal weight and body mass index, and with lower infant birth weight. After stepwise logistical regression, successful induction of labor was most closely associated with preripening cervical dilation. Postripening cervical dilation also correlated more closely with successful induction than other measures, including the Bishop score. Similar results were obtained for the outcome of vaginal delivery.
The authors conclude that cervical dilation is a predictor of successful labor induction and vaginal delivery. The study results indicated that the Bishop score and its component cervical measures, and nulliparity were not significantly associated with these outcomes when adjusted for cervical dilation. The authors advocate the use of simpler measures of cervical status in the assessment of patients for induction of labor.
ANNE D. WALLING, M.D.
Williams MC, et al. The value of the cervical score in predicting successful outcome of labor induction. Obstet Gynecol 1997 November;90:784-9.
Strategies for Choosing Antidepressant Medications
All antidepressants are equally effective in treating depression, and all have approximately equivalent rates of onset of action. Pathare and Paton review the combination of factors that affect the choice and effectiveness of antidepressant medications, including clinical and patient characteristics, side-effect profile and experience of the prescribing physician.
Because certain types of depression respond particularly well to specific medications, obtaining a detailed diagnostic history is important. A previous experience of similar episodes of depression and the response of specific agents can be particularly helpful (see the accompanying figure). Patients with mixed anxiety and depression respond well to selective serotonin reuptake inhibitors. Patients with agitated depression may do best with a sedating tricyclic agent such as amitriptyline; the best choice for a patient with atypical depression may be monoamine oxidase inhibitors, and a stimulating agent such as imipramine may help when social withdrawal is a prominent feature of depression. Patients with depression that is accompanied by delusions and psychotic features often have a poor response to antidepressants when used alone, but the addition of an antipsychotic drug greatly improves the outcome.
The risk of suicide in patients with depression is difficult to predict and may be minimized by providing adequate dosages of an appropriate antidepressant and regulating the quantity of the medication provided, particularly if tricyclic antidepressants are used. Selective serotonin reuptake inhibitors are safer if the potential for a patient to overdose exists, but these drugs are significantly more expensive than tricyclic antidepressants.
Too small a dosage of antidepressants given for too short a time is the most common problem with the use of antidepressants. Approximately 70 percent of patients respond to the first agent administered if it is given in therapeutic doses (such as amitriptyline at 150 mg daily or fluoxetine at 20 mg daily) for six to eight weeks. Noncompliance is a frequent cause of the patient's apparent failure to respond to therapy. If the patient does not improve following an adequate trial of therapy given at an optimal dosage, options include increasing the dosage if the patient can tolerate it or changing the antidepressant to an agent of a different chemical class. Up to 15 percent of patients respond to a change in medications at this stage.
The risk of relapse following a single episode of depression is approximately 65 percent within the first year in patients who stop taking medication. As only 15 percent of those who continue to take antidepressant medication relapse, the authors conclude that younger patients should continue medication for at least six months following remission of symptoms. Elderly patients and those with recurrent symptoms should be maintained on antidepressant medication for at least two years after symptoms are controlled.
ANNE D. WALLING, M.D.
Pathare SR, Paton C. ABC of mental health. Psychotropic drug treatment. BMJ 1997 October;315:661-4.
Management of Incidental Pituitary Microadenomas
The incidental finding of a pituitary microadenoma (less than 10 mm in size) is not uncommon. Studies have suggested a 10 percent prevalence of pituitary microadenomas in the general population. Current recommendations for the evaluation of such an incidental finding are controversial. Some experts suggest extensive laboratory evaluation to determine levels of prolactin, growth hormone, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, luteinizing hormone and follicle-stimulating hormone. Serial magnetic resonance images (MRI) may also be recommended to determine whether a change in the lesion has occurred. King and associates studied the cost effectiveness of four management strategies for incidentally discovered pituitary microadenomas.
The authors addressed the following four questions: (1) Does an incidental pituitary microadenoma put the patient at increased risk for an adverse outcome? (2) Can patients with treatable syndromes be accurately identified? (3) Is the treatment of these syndromes more effective in presymptomatic patients? (4) Do the beneficial effects of presymptomatic detection and treatment justify the costs incurred?
The following management strategies were assessed: (1) expectant management, with further testing performed only if endocrinologic or neurologic symptoms such as amenorrhea, galactorrhea or visual field problems develop; (2) prolactin screening, with hyperprolactinemia confirmed by a repeat test and treated with bromocriptine; (3) an endocrinologic screening panel that includes determination of prolactin, somatomedin C (insulin-like growth factor) and cortisol levels after administration of 1 mg of dexamethasone; and (4) follow-up of MRI scans. The model included issues such as the expected natural history of an incidental asymptomatic pituitary microadenoma, test characteristics, outcomes of pharmacologic and surgical interventions, quality of life, and costs of testing and treatment.
Determination of the prolactin level was found to be the most cost-effective management strategy for patients with asymptomatic, incidental pituitary microadenomas. An endocrine screening panel and follow-up MRI provided slightly greater quality-adjusted survival than expectant management, although the cost increased substantially.
The authors conclude that, while this study does not resolve the debate about conservative versus aggressive management of these lesions, it does provide evidence for a reasonable approach to patients with asymptomatic pituitary microadenomas. They note that the low prevalence of other endocrinopathies in patients with incidental pituitary microadenomas suggests that further evaluation of patients with normal prolactin levels confers little benefit and is not cost effective. Follow-up with MRI scanning provides no better clinical results than hormone screening.
JAMES NUOVO, M.D.
King JT Jr, et al. Management of incidental pituitary microadenomas: a cost-effectiveness analysis. J Clin Endocrinol Metab 1997 November;82:3625-32.
Viremia Predicting Response to Interferon Therapy in Hepatitis C
Hepatitis C virus infection often leads to chronic hepatitis, which may progress to cirrhosis and/or hepatocellular carcinoma. Interferon alfa is the only currently known effective therapy, but it requires a minimum of six months of treatment, and only a small percentage of patients receive long-term benefits. Although several factors, including age, absence of cirrhosis, viral genotype and other variables that influence treatment outcome have been identified, a better predictor of response to treatment would be useful. Gavier and associates analyzed viral status after initiation of interferon therapy as a predictor of treatment outcome.
One hundred eighty-one patients with hepatitis C virus infection were followed for a median of 49 months to find the predictive value of eliminating viremia one month into treatment. The study subjects, who had elevated alanine aminotransferase (ALT) levels and histologic evidence of chronic hepatitis, had been treated with a one-year course of interferon alfa therapy and were followed up with measurements of ALT and serum hepatitis C virus RNA concentrations. A sustained response--normal liver function tests--was obtained in 51 of the patients (28 percent). Of 132 patients who had been tested for hepatitis C virus RNA after one month of treatment, hepatitis C virus RNA was cleared from serum in 68. Of these 68 patients, one half had a sustained response, and one half were nonresponders. Among the 64 subjects who remained viremic after one month of therapy, only three (4.7 percent) responded to treatment.
Follow-up demonstrated that variables associated with a higher probability of response to treatment include younger age, lower body mass, higher pretreatment levels of ALT, lower pretreatment levels of gamma-glutamyl transpeptidase, absence of cirrhosis, clearance of hepatitis C virus RNA at the first or third month of treatment, and lower pretreatment viral loads. The only procedure useful in isolated cases appears to be the hepatitis C virus RNA count after one month of treatment. Clearance of hepatitis C virus RNA seemed to have moderate predictive value for sustained response, while persistence of hepatitis C virus RNA in serum at one month of treatment appears to much more accurately predict nonresponse.
The authors conclude that early monitoring of hepatitis C virus RNA during interferon treatment may help the physician make therapeutic decisions in individual patients. When hepatitis C virus RNA remains positive at one month of treatment, the probability of a sustained response to interferon therapy is very low (less than 5 percent). When viremia becomes negative, the probability of sustained response averages 50 percent, varying from 70 percent to 20 percent depending on age. Withdrawal of interferon therapy in patients who have persistent hepatitis C virus RNA counts at one month of treatment should be considered. In selected patients, continuation of therapy in the face of persistent viremia might be appropriate for other treatment benefits such as slowed progression of cirrhosis and decreased risk of hepatocellular carcinoma.
RICHARD SADOVSKY, M.D.
Gavier B, et al. Viremia after one month of interferon therapy predicts treatment outcome in patients with chronic hepatitis C. Gastroenterology 1997 November;113:1647-53.
Decision tree for drug treatment of depression. (SSRIs=selective serotonin reuptake inhibitors)
Pulmonary Function in Cases of Stable Chronic Bronchitis
Chronic bronchitis is characterized by increased sputum production with decreased sputum clearance. Several studies have shown that the amount of bronchial surfactant is decreased in persons with chronic bronchitis. Anzueto and associates conducted a prospective randomized double-blind study to determine whether aerosolized exogenous surfactant could improve pulmonary function by increasing sputum clearance in patients with chronic bronchitis.
Patients were included in the study if they had a diagnosis of chronic bronchitis, had at least a 10-pack-year history of smoking and had a forced expiratory volume in one second (FEV1) of 40 to 70 percent of normal. Patients were excluded if they had asthma, a pulmonary disease other than bronchitis or a recent acute pulmonary infection. Patients received nebulized isotonic saline or synthetic surfactant in a dosage of 202.5 mg per day, 607.5 mg per day or 1,215 mg per day for two weeks. Pulmonary function testing (including FEV1 and forced vital capacity [FVC]) was performed and respiratory symptoms were reviewed during the study. Sputum analysis was performed three times, on day zero, day 14 and day 21.
Sixty-six patients were in the surfactant group and 21 were in the control group. Of these, 79 completed the study. No significant changes in spirometry were reported in patients taking placebo or the 202.5 mg per day of surfactant. The group taking 607.5 mg per day of surfactant showed significant improvement in FEV1 and FVC by days 14 and 21. Similarly, the group taking 1,215 mg per day of surfactant showed an increase of 18 percent in the FEV1 by day 21. Respiratory symptoms (cough frequency, sputum production and global condition) improved in all groups, but not significantly more in the surfactant group than in the placebo group. Sputum analysis showed a dose-dependent increase in mucociliary transportability.
The authors conclude that use of aerosolized surfactant, especially at a dosage of 607.5 mg per day, improved FEV1 and FVC before and after use of the bronchodilator. This improvement lasted for at least one week after treatment. The effect was most likely a result of improved sputum clearance, and larger studies are needed to verify the usefulness of this treatment in patients with chronic bronchitis.
GRACE BROOKE HUFFMAN, M.D.
Anzueto A, et al. Effects of aerosolized surfactant in patients with stable chronic bronchitis. A prospective randomized controlled trial. JAMA 1997 November 5;278: 1426-31.
Withdrawing Elderly Patients From Chronic Diuretic Therapy
Approximately 20 percent of elderly patients use long-term diuretic therapy, mainly for heart failure and hypertension. In addition to cost, prolonged use of these agents is associated with the risk of hypokalemia, hyponatremia, dehydration and cardiac arrest. Walma and colleagues investigated the effect of withdrawal of diuretics in healthy elderly patients with stable blood pressures.
From eight Dutch general practices, the authors recruited 202 healthy elderly patients who had taken diuretics for at least six months and in whom no heart failure or current elevations of blood pressure were present. The patients were assessed at home on two occasions and were then randomly assigned to placebo (withdrawal group) or continuation of diuretic treatment (control group). The randomization was stratified by age and type of diuretic to ensure comparability between the groups. Patients were visited at home by physicians at two days, at one week and at two weeks. Further follow-up was performed at one, three and six months. At each visit, possible symptoms of heart failure were assessed using standardized scoring scales, and blood pressure levels were measured under standardized conditions. Compliance was verified by tablet counts and patient interview at every visit and by assessment of serum diuretic concentrations at the beginning and end of the study.
In the first six months, 25 patients in the withdrawal group and four in the control group developed heart failure symptoms of sufficient severity to merit diuretic therapy. In addition, 25 withdrawal patients and nine control patients met criteria for diuretic therapy for other indications. Mean blood pressure elevations in the withdrawal group were 13.5 mm Hg systolic and 4.6 mm Hg diastolic. The need for diuretic therapy was more marked in women but did not appear to be related to any other patient variable. Most patients developed symptoms within four weeks of withdrawal. No patients suffered serious adverse effects or required hospital admission.
The authors conclude that withdrawing elderly patients from long-term diuretic therapy resulted in symptoms of heart failure and/or increased blood pressure in most cases and that approximately one half of such patients should restart diuretic therapy. The authors caution that any attempt to withdraw established diuretic therapy in the elderly must be done under careful monitoring, especially during the first four weeks, and should be restricted to patients with hypertension and noncardiac edema.
ANNE D. WALLING, M.D.
Walma EP, et al. Withdrawal of long term diuretic medication in elderly patients: a double blind randomised trial. BMJ 1997 November;315:464-8.
Routine Pathologic Examination of Excised Tissue Specimens
Family physicians routinely perform minor surgery to remove tissue. The conventional advice that all tissue should be examined pathologically has been challenged on the grounds that this is a wasteful use of resources. Lowy and colleagues studied 257 general practices in England to assess the rate of detection of clinically important lesions and the costs associated with a policy to examine all tissues.
Nineteen regional pathology laboratories in England agreed to take part in the study. For each laboratory, between eight and 18 referring general practices were randomly selected to participate. These practices agreed to send all tissue removed during a six-month period. The volume and histologic significance of these specimens were compared with tissue sent by the same practices during a six-month period in the previous year.
The 257 practices included 914 general practitioners who submitted 10,153 specimens during the study period. This was a 29 percent increase over the number of specimens submitted during the control period. During the study period, 98 premalignant lesions were detected; 91 lesions were detected during the control period. For malignant lesions, 188 were submitted during the study period and 204 were submitted during the control period. These differences were not statistically significant. The number of referrals for viral warts, seborrheic keratoses and ingrown toenails increased significantly during the study period (2,886 compared with 1,729 during the control period); referral of other benign lesions also increased significantly, from 2,409 during the control period to 2,720 during the study period.
The authors conclude that a policy of "send all tissue" resulted in a significantly increased workload for the laboratories, all of which was accounted for by nonserious lesions. No evidence was found of a change in the detection rate of malignant or premalignant lesions. The authors believe that the study validates the premise that family physicians can appropriately biopsy and send malignant lesions for pathologic examination while selectively discarding other material. In particular, the authors discuss concerns of underdiagnosis of melanoma under a policy of "selective" submission of tissue for pathologic diagnosis. In Great Britain, the impact of increased patient education, availability of clinics for pigmented lesions and comprehensive general practitioner coverage of the population is believed to provide effective mechanisms for detection of melanoma. The authors recommend continuing to send selected specimens from general practices to pathology laboratories and estimate the annual savings to be nearly $7 million.
ANNE D. WALLING, M.D.
Lowy A, et al. Is histological examination of tissue removed by general practitioners always necessary? Before and after comparison of detection rates of serious skin lesions. BMJ 1997 November;315:406-8.
Rates of Compliance with Home Nebulizer Therapy
Home nebulizer therapy is frequently recommended for use in patients with chronic obstructive pulmonary disease (COPD) who do not respond adequately to therapy with a metered-dose inhaler. Home programs are established, and patients and family members are educated about using the nebulizer despite the fact that few studies have assessed the compliance of patients with this treatment regimen. Corden and associates evaluated the significance of compliance in patients receiving home nebulizer therapy.
The four-week study included 93 patients who were already established on a home nebulizer program. Home nebulizers were installed that recorded the date, time, duration of treatment and inhalation time without patient knowledge of the recording capabilities. Patients completed a quality-of-life survey specifically designed for COPD patients before the study period and at its conclusion. Compliant patients were defined as patients who took at least 70 percent of the recommended treatments (in those prescribed up to four treatments daily) or at least 60 percent of treatments (in those prescribed five or more treatments daily).
Only 44 percent of the patients were compliant with their regimen. In over one half of the patients, there were times that the nebulizer was turned on but no inhalations were performed. Also, 21 percent of the patients did not use the equipment at all on at least 50 percent of days during the study period. The quality-of-life data showed a direct correlation between higher compliance and higher scores on the survey.
The authors conclude that there was poor compliance with home nebulizer therapy, which had a significant impact on the quality of life in patients with COPD. Poor compliance in COPD patients has been shown to increase rates of morbidity. It is vital that physicians assist their patients to comply with home nebulizer therapy in order to improve their quality of life and decrease the impact of this disease on the patients.
KARL MILLER, M.D.
Corden ZM, et al. Home nebulizer therapy for patients with COPD. Patient compliance with treatment and its relation to quality of life. Chest 1997 November;112: 1278-82.
Order of Sampling as a Factor in the Quality of Pap Smears
Current techniques for obtaining a Papanicolaou smear are reported to have false-negative rates of up to 50 percent. Sampling technique may influence this rate by failing to obtain cells or by yielding samples that contain blood or debris. Eisenberger and colleagues investigated the usefulness of a clinical recommendation that obtaining the ectocervical sample before the endocervical sample improves the quality of the Pap smear.
The study was conducted at a university gynecology clinic. During one phase of the study, residents obtained the endocervical sample before the ectocervical sample. During the other phase, the ectocervical sample was obtained first. An endocervical brush was used to obtain the endocervical sample, and an Ayre spatula was used to obtain the ectocervical sample. The 500 samples obtained by each sequence were reviewed by the same team of cytotechnologists and pathologists, who were blinded as to the order of sampling.
Inadequate samples were defined as those without an endocervical component, smears that were too thick or were obscured by blood or inflammation, and those with air-drying artifact. When the endocervical sample was obtained first, 405 (81 percent) of the smears were adequate. When the ectocervical sample was obtained first, 410 (82 percent) of the samples were adequate.
The two sequences for obtaining cells differed significantly in the proportion of smears obscured by blood. When endocervical samples were obtained first, 22 (4.4 percent) of the samples were obscured by blood. In contrast, this was a problem in only three (0.6 percent) of the samples in which ectocervical cells were obtained first. The difference in the number of low- or high-grade squamous intraepithelial lesions identified by the two techniques was statistically significant. With ectocervical sampling preceding endocervical sampling, 55 (11 percent) of the samples revealed such lesions, compared with 35 (7 percent) of the samples when the endocervical sample was obtained first.
The authors conclude that using the Ayre spatula to obtain the ectocervical sample first, followed by use of the endocervical brush to obtain the endocervical sample, improves the quality of Pap smears, primarily by reducing the number of samples that are obscured by blood.
ANNE D. WALLING, M.D.
Eisenberger D, et al. Order of endocervical and ectocervical cytologic sampling and the quality of the Papanicolaou smear. Obstet Gynecol 1997 November;90:755-8.
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