Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction.

BACKGROUND: This study was designed to investigate the tolerability, safety, and effect on left ventricular function of a new long-acting preparation of metoprolol, metoprolol succinate (CR/XL). METHODS AND RESULTS: Sixty patients were randomly assigned with a 2:1 ratio, drug versus placebo, administered with a gradually increasing dose of 12.5 to 150 mg of blinded medication during an 8-week period and continued for 6 months. The average peak dose achieved was 99 mg and 132 mg in the metoprolol succinate and placebo groups, respectively. The drug was well tolerated and there was no significant difference in drug withdrawals, New York Heart Association class, or quality of life assessment. The increase in left ventricular ejection fraction measure at baseline and 6 months measured by radioisotopic ventriculography was greater in the metoprolol succinate group (27. 5% to 36.3%) than in the placebo group (26% to 27.9%) (P <.015). Examination of serial Holter electrocardiographic recordings indicate that metoprolol succinate therapy was associated with a significant (P <.05) decrease in total ventricular ectopy at 8 weeks of therapy and a decrease in ventricular couplets and nonsustained ventricular tachycardia at 8 through 26 weeks of therapy. No changes were observed in plasma norepinephrine during therapy except a transitory significant (P <.05) increase in N terminal proatrial natriuretic factor at 8 weeks in the metoprolol succinate group. CONCLUSIONS: This study indicates that treatment with metoprolol succinate for a 6-month period is safe and well tolerated and is associated with an increase in left ventricular ejection fraction and a decrease in ventricular ectopic beats.

Clinical use of nebulized budesonide inhalation suspension in a child with asthma.

Childhood asthma contributes to significant morbidity among patients and significantly impacts the quality of life and daily routines of their caregivers. The parents or caregivers assume responsibility for tasks that children are too young to perform; this often includes daily administration of controller medications and nightly administration of reliever medications. Most young children do not have the coordination or understanding to effectively use pressurized metered-dose inhalers or inhalation-driven devices; thus nebulizer therapy often is preferred for children younger than 4 years of age. Budesonide inhalation suspension will be the first inhaled corticosteroid available for children younger than 4 years of age and the first inhaled corticosteroid for delivery by nebulization in the United States. This is a case report of a 3-year-old boy who received budesonide inhalation suspension as part of several double-blind and open-label studies evaluating the drug. Before study entry, the boy was experiencing more breakthrough wheezing episodes at night than the parents were used to, resulting in an increase in nighttime awakenings that required nebulizer therapy. These nighttime awakenings had a substantial impact on the quality of life of the entire family and interfered with the parents' ability to function at work. Even though they wanted to have more children, this situation discouraged them from doing so. Budesonide inhalation suspension improved overall asthma control and was well tolerated. The boy had a decrease in nighttime symptoms and an increase in both height and weight percentiles for his age. Importantly, use of budesonide inhalation suspension in this boy eased the management of severe asthma and improved the quality of life of the entire family. The parents subsequently decided to have a second child. Budesonide inhalation suspension represents a major breakthrough for infants and young children by providing a formulation that, on approval, can be delivered reliably by nebulizer for effective maintenance treatment of persistent asthma.

Antihypertensive medication compliance in African-American stroke patients: behavioral epidemiology and interventions.

Hypertension is a major cause of stroke in the African-American community, and lack of control of hypertension appears to be common. Improving compliance to antihypertensive therapy in African-American stroke patients could have a significant impact on recurrent stroke rates. Little is known about factors affecting compliance in this community and which interventions would be effective in improving compliance. Health behavior models which assess the patient's perception of stroke and hypertension, barriers to the desired behavior, perception of ability to perform the behavior, perception of others' acceptance of the behavior and the patient's behavioral stage could be used to tailor interventions to improve compliance. A plan to improve compliance should take into account the target population's baseline rates of compliance, perception of need for intervention and risk factors for noncompliance.

Stroke survival after discharge from an acute-care hospital.

BACKGROUND AND PURPOSE: Survival after a stroke is likely to be best for patients well enough to be sent home but the relative risk of dying if patients do not qualify for a home discharge has not been well studied. We investigated the survival prognosis after an initial stroke depending on the facility to which the patient was discharged after an acute initial stroke. METHODS: All patients were enrolled between July 1, 1987, and August 1, 1989, and were followed up to 4 years (mean of 24 months) until death, second stroke, or the end of the study. RESULTS: Among 662 patients who were discharged alive after hospitalization with an initial stroke, 128 (19%) went to a nursing home, 17(3%) to a short-term hospital, 140 (21%) to a rehabilitation facility, and 375 (57%) went home (discharge destination unknown for 2 patients). Compared to patients sent home after taking age, sex, selected baseline comorbidities, length of hospital stay, and neurological deficits into consideration, results from Cox proportional hazards model indicated that patients sent to a nursing home had 2.6 times greater risk of dying (95% CI = 1.81-4. 15) while those who were discharged to a rehabilitation facility had a death hazards ratio of 1.1. CONCLUSIONS: Mortality was greatest in the early months after discharge and decreased thereafter. Since the analysis was adjusted for age, sex, comorbidity, length of hospital stay, and number of neurological deficits, quality of care in a nursing home setting may account for the mortality difference but other factors such as social support network and living will instructions also need to be investigated.

Disposition after acute stroke: who is not sent home from hospital?

BACKGROUND: Known demographic and clinical characteristics of stroke survivors that affect selection of the facility to which they are discharged after hospitalization for an acute stroke are, for the most part, not population based and therefore may be unrepresentative. We present an analysis of such characteristics using the Lehigh Valley stroke cohort which is population based. METHOD: We enrolled patients within 1 month of onset of their initial acute stroke who were hospitalized between 1987 and 1989 at one of the eight hospitals in the Lehigh Valley, and 662 patients were discharged alive. The facility to which they were discharged was known for 660. Data on age, sex, presence of five selected comorbidities (hypertension, myocardial infarction, cardiac arrhythmia, diabetes mellitus and transient ischemic attacks), length of hospitalization and neurologic deficits from the stroke were systematically collected on standardized forms. Polytomous logistic regression was used to determine the factors associated with not being discharged home. Relative risk (RR) associated with discharge to a nursing or rehabilitation facility for each independent predictor was calculated using as the referent, those who went home. RESULTS: Older age was a statistically significant predictor of not being sent home (RR = 1.2 for nursing home placement), but gender and living with a spouse were not. Having a selected comorbidity did not increase the RR of not being sent home regardless of the type, nor did risk of not being sent home increase with more than one illness. Considering neurologic deficits from the stroke, patients with lower extremity weakness had a 2.6- and 3.5-fold risk of being sent to a nursing or a rehabilitation facility, respectively, compared to those without such weakness while for those with upper extremity weakness, the RR was 1.5 and 4.9, respectively. Language deficit imposed a RR of 3.1 and 2.3 of going to a nursing or rehabilitation facility, respectively. Right facial weakness also emerged as a significant risk factor for not being discharged home, perhaps because of its association with language deficit. The longer a patient was hospitalized after a stroke, the less likely it was that such a patient would go home (RR = 1.1/hospitalization day). CONCLUSION: Using population-based data on stroke survivors, our study showed the characteristics of patients who are less likely to be discharged home and, instead, are discharged to a nursing or a rehabilitation facility. Data like ours which were population based may be useful in discharge planning for stroke patients by policy makers and health care providers.

The clomethiazole acute stroke study in ischemic, hemorrhagic, and t-PA treated stroke: Design of a phase III trial in the united states and canada.

Clomethiazole is a drug with sedative properties effective in laboratory studies of brain ischemia. A large European multicenter trial of clomethiazole in acute stroke patients showed no benefit overall, but subgroup analysis indicated that patients with large infarctions may have benefited from treatment. To confirm this preliminary finding, we have designed CLASS-IHT, the Clomethiazole for Acute Stroke Study in Ischemic, Hemorrhagic and TPA Treated Patients, to be conducted in North America. Patients who suffer large cerebral infarctions and present within 12 hours of symptom onset are eligible. Patients will be randomized to receive clomethiazole 68 mg/kg over 24 hours or vehicle, using a dosing scheme based on the pharmacokinetics measured in the first trial. Outcome assessments include stroke scales, the Barthel Index, and lesion volume. An additional study of health economic outcomes is planned. The primary endpoint for CLASS-I will be the Barthel Index 90 days after stroke. A total of 1,200 patients will be randomized to CLASS-I, and in safety-only trials, 200 patients with cerebral hemorrhage will be randomized into CLASS-H and another 100 to 200 patients will be randomized into CLASS-T. The details of the protocols for all three studies are presented.

Stroke recurrence in diabetics. Does control of blood glucose reduce risk?

BACKGROUND AND PURPOSE: Patients with diabetes are at increased risk of stroke. Risk might be reduced if blood glucose level were controlled. METHODS: In a population-based study, we enrolled 621 patients within a month of an initial ischemic stroke and followed them regularly twice annually; 198 were diabetic. We monitored blood glucose level in 142 (72%) using glycosylated hemoglobin (HbAlc). Recurrent stroke frequency was determined by history, examination, and medical records. Cox proportional hazards models were used to examine the relationship between risk of recurrent stroke and HbAlc level. The models included interaction with time-dependent HbAlc level and history of diabetes, selected medical comorbidities, age, and sex. HbAlc level was analyzed as both a continuous and a dichotomous variable (ie, controlled versus uncontrolled); "controlled" was defined with different cut points. RESULTS: All but 17 patients (12%) whose blood glucose was monitored were well controlled (HbAlc < 8%). HbAlc level was not associated with increased risk of stroke recurrence (hazard ratio [HR], 0.87 per 1% increment in HbAlc; 95% confidence interval [CI], 0.623 to 1.219), nor was there a trend toward increased risk of recurrent stroke as the cut point defining "controlled" increased: with HbAlc at < 6%, the HR for the uncontrolled group was 0.51 (95% CI, 0.176 to 1.503); at < 7%, it was 0.43 (95% CI, 0.089 to 1.923); and at < 8%, it was also 0.43 (95% CI, 0.057 to 3.317). CONCLUSIONS: Among diabetic patients with an initial stroke, no association between HbAlc level over time and risk of stroke recurrence was found. However, most patients in this cohort were well controlled, and any adverse effect of poor control could not be adequately tested.

Profile of children requiring emergency treatment for asthma.

BACKGROUND: Emergency department care for asthma is expensive and continuity of care is often inefficient. Identification of patients-at-risk for emergency treatment is required in order to intervene before visits to the emergency department. OBJECTIVE: To identify the antecedent factors in patients requiring emergency department treatment for wheezing and to determine the level of care before emergency visits. METHODS: A prospective survey of patients treated for wheezing in the emergency department of an academic children's hospital from January 1, 1994 to December 31, 1994. Data were compiled from a data from completed from the information obtained from the medical record, phone calls and letters. RESULTS: During 1994, 1474 patients were treated for asthma and accounted for 1870 visits to the emergency department. Thirty-six percent of the total number of visits were made by 16% of the patients who made repeat visits. Two-thirds of the patients were 5 years of younger. Over 190 patients had been hospitalized for wheezing during the preceding 12-month period. Forty-four percent of the patients were referred to the emergency department by primary care physicians and 6.7% were referred by asthma specialists, either allergists or pulmonologists. The major predisposing factor was a family history of asthma in 70%. Beta agonists were the medications most frequently used prior to the emergency visits. Inhaled corticosteroids were used daily by 16% of the patients and oral corticosteroids were used daily by 7% of the patients. CONCLUSION: Thirty-six percent of the visits were due to 16% of patients who were seen repeatedly in the emergency department for wheezing and a number of patients (192) had been admitted previously for wheezing. These findings suggest that there is a subset of patients who are known to have recurrent wheezing, but lack adequate management to avoid expensive hospital services. Very few of these patients were followed by asthma specialists and there was a marked underuse of anti-inflammatory drugs. This study characterized a subset of patients-at-risk for requiring emergency treatment for wheezing. There is a need to institute aggressive interventions to improve the quality of care and prevent costly emergency department visits.

Transient ischemic attack and risk of stroke recurrence: The Lehigh Valley Recurrent Stroke Study.

We investigated the effect of transient ischemic attack occurring both before and after an initial stroke on risk of recurrent stroke in a population-based study. In the Lehigh Valley Recurrent Stroke Study, patients were enrolled between July 1987 and August 1989 and followed up regularly at about 6-month intervals for up to 4 years (mean, 2 years). In addition to history of transient ischemic attack before and after the initial stroke, information on comorbidities including hypertension, myocardial infarction, cardiac arrhythmia, and diabetes mellitus was collected at the baseline visit and at follow-up visits. The 621 patients with an initial ischemic stroke constituted the cohort analyzed in this report. A history of transient ischemic attack was present at enrollment in 114 (18.4%) patients. During follow-up, 20 patients experienced a transient ischemic attack, and 77 had a recurrent stroke. Using a Cox proportional hazards model taking comorbidities, sex, and age into account, we analyzed the relationship between transient ischemic attack and recurrent stroke in the 503 patients with at least one follow-up visit. History of transient ischemic attack before the initial stroke was associated with a decreased risk of recurrent stroke (Hazards ratio, 0.3; 95% confidence interval, 0.08 to 0.86; P=.03), whereas a new transient ischemic attack after the initial stroke was associated with an increased risk of recurrent stroke (Hazards ratio, 11.7; 95% C.I. confidence interval=3.45 to 39.83; P=.0001).

Prognosis for survival after an initial stroke.

BACKGROUND AND PURPOSE: We studied prognosis for survival after an initial stroke in 662 patients who survived at least 30 days after onset while taking into account age, sex, the number of neurological deficits from the initial stroke, stroke type, and five selected medical conditions: hypertension, myocardial infarction, cardiac arrhythmia, diabetes mellitus, and history of transient ischemic attacks. METHODS: All patients were enrolled between July 1, 1987, and August 1, 1989, and were followed regularly at about 6-month intervals until death or the end of the study (mean of 24 months). RESULTS: At 6 months, 90.8% of the 30-day stroke survivors were still alive. At 1, 2, 3, and 4 years, the cumulative survival rates were 86.9%, 78.7%, 73.2%, and 72.0%, respectively. Older age and the number of neurological deficits at onset of initial stroke increased risk of death. Compared with patients of the same age, sex, number of neurological deficits, and comorbidities, increased risk of death is present among those with myocardial infarction, cardiac arrhythmia, and diabetes mellitus. Hazard ratios were 1.7 (P = .006), 1.5 (P = .023), and 1.4 (P = .059), respectively. Hypertension and transient ischemic attacks were not significantly associated with increased mortality. CONCLUSIONS: This study clarifies prognosis for survival after an initial stroke by taking into account other confounding variables that could also contribute to risk of death.

Hypertension and risk of stroke recurrence.

BACKGROUND AND PURPOSE: Hypertension is a risk factor for initial stroke, but its relation to stroke recurrence is unclear. Therefore, we sought to analyze the effect of hypertension and its control on risk of stroke recurrence. METHODS: Within 1 month of onset, a population-based cohort of 662 patients from the Lehigh Valley with an initial stroke were enrolled. Hypertension was determined at enrollment by history. Blood pressure was also measured at enrollment and at each follow-up at 4- to 6-month intervals for up to 48 months (mean, 24 months). Stroke recurrence was verified by history, examination, and review of medical reports. Various criteria for control of blood pressure were defined. History of hypertension, measured blood pressure, and its control were analyzed in relation to stroke recurrence frequency using Kaplan-Meier and univariate, multivariate, and time-dependent Cox proportional hazards models. RESULTS: At enrollment, 59.4% of the cohort had a history of hypertension and 81 patients had a second stroke. Those with a history of hypertension had a significantly higher stroke recurrence rate than those without such a history (P = .01). Among those with measured diastolic blood pressure at enrollment > or = 95 mm Hg, 43% had a stroke recurrence by the end of the study compared with only 19% below this cutoff (P = .005). Recurrence risk was reduced in a multivariate analysis as quality of diastolic blood pressure control increased (relative risk = 8.4, 3.9, and 2.0 among those with poor, fair, and good control, respectively, compared with nonhypertensive subjects). Systolic blood pressure and its control appeared less or not significantly associated with stroke recurrence. CONCLUSIONS: History of hypertension and elevated measured diastolic pressure after the initial stroke were associated with an increased risk of second stroke. Controlling diastolic pressure substantially reduced this risk.

A multifactorial analysis of risk factors for recurrence of ischemic stroke.

BACKGROUND AND PURPOSE: Risk factors for stroke recurrence have usually been evaluated as single variables. This study is a multivariate analysis of five risk factors (hypertension, myocardial infarction, cardiac arrhythmia, diabetes mellitus, and transient ischemic attacks) for second stroke after an initial ischemic stroke. METHODS: Six hundred twenty-one patients with an acute ischemic stroke were followed prospectively first at 4 months after onset and then at approximately 6-month intervals until death, recurrence of stroke, or the end of the study. The five risk factors were measured at each visit. A Cox multifactorial regression analysis was conducted using the risk factor status at enrollment and adjusted for age and sex. RESULTS: Follow-up averaged 24 months (range, 1 to 48 months). Men comprised 52% of the cohort and were slightly older; 97% of the cohort was white, and 57% had multiple risk factors. Hypertension occurred in 59%, cardiac arrhythmia in 47% (of which 16% had atrial fibrillation), diabetes mellitus in 30%, myocardial infarction in 25%, and transient ischemic attacks in 18%. Only history of hypertension and atrial fibrillation by electrocardiogram were associated with increased risk of second stroke independently and significantly (P = .01 and P = .04, respectively). CONCLUSIONS: Among the five factors analyzed, control of hypertension and atrial fibrillation appear to offer the greatest chance of reducing risk of stroke recurrence after an ischemic stroke.

Nonfatal systemic allergic reactions induced by skin testing and immunotherapy.

Skin testing and immunotherapy with allergens can induce systemic allergic reactions. In order to identify factors associated with systemic allergic reactions, a prospective study was conducted from 1976-1989 with more than 10,000 patients being tested and a total of 513,368 injections being recorded. Our study showed that the probability of inducing systemic allergic reactions by skin testing was less than 0.02% and the probability of systemic allergic reactions caused by immunotherapy was 2.9%. The female to male ratio was 3 to 2. The highest incidence of systemic allergic reactions was in patients between the ages of 16 to 39 years of age. The majority of systemic allergic reactions occurred when patients were on increasing doses rather than maintenance doses. More than 95% of systemic allergic reactions were associated with pollens and most of them happened between the concentration of 100 and 1000 PNU/mL. There was no increased incidence during grass or ragweed pollination seasons in those patients who received grass or ragweed injections during the respective seasons. Only 50% of systemic allergic reactions developed within 30 minutes after injections. The three most important factors determining the incidence of systemic allergic reactions are the type of allergens, the "rate" of increase of allergen concentrations, and sensitivity of the patients to allergens. The prick test at initial allergy assessment can be used to "rule out," with a high degree of certainty, the likelihood of systemic allergic reactions. The prick test is easy to perform and it is cost-effective. Prick tests and RAST together are helpful in identifying the patients and the allergens at higher risk of systemic allergic reactions.

Compliance with allergen immunotherapy.

Immunotherapy has been used for the treatment of allergic rhinitis since the turn of this century. The purpose of this study was to assess the compliance with immunotherapy in a medical center. The charts of 315 patients aged 5 to 18 years, who were prescribed immunotherapy for treatment of allergic rhinitis for at least 1 year before the study, were selected by computer and reviewed. The first analysis consisted of using a log-linear analysis in order to investigate the relationship between source of payment (private or nonprivate), gender, and race. All main effects and interactions were entered into the model (P < .01). The second analysis consisted of using a log-linear analysis to investigate the relationship between the presence/absence of pollen, mold, mite, and animal IgE antibodies, and compliance (model, P < .05). Two hundred fifty-eight patients were private and 57 were nonprivate. Fifty-nine percent (n = 152) of private patients and 46% (n = 26) of nonprivate patients were compliant. Of the 315 patients with allergic rhinitis, 52 also had asthma and 34 had atopic dermatitis. Sixty-one percent of the asthmatic patients and 47% with atopic dermatitis were compliant. Compliance was not increased by the number of allergens to which a patient was allergic. Males were slightly more compliant than females, caucasians were more often private patients and non-whites were more often nonprivate patients. Private patients were more complaint with immunotherapy than nonprivate patients.

The Lehigh Valley Recurrent Stroke Study: description of design and methods.

A community-based, prospective study was carried out in the Lehigh Valley to determine how 5 selected risk factors and their control affected the frequency of stroke recurrence and death after an initial stroke. The initial stroke was verified clinically and by computerized tomography. Between 1987 and 1989, 662 patients with an initial stroke were enrolled and followed regularly every 4-6 months for up to 7 visits. The average follow-up period was 2 years. The risk factors selected included hypertension, myocardial infarction, cardiac arrhythmia, diabetes mellitus and transient ischemic attacks. Interim death and its cause were noted. Surviving patients were interviewed and examined to determine whether a second stroke has occurred. At enrollment, 51.4% of the cohort was male. The average age of men was 69.6, while women were older, averaging 74.3 years. Stroke types were thrombosis, 14%; embolus, 23%; lacune, 9%; nonspecific infarct, 48%, and intracerebral hemorrhage, 6%. There were 138 deaths (21%) and 81 second strokes (12%) during follow-up. The frequency of risk factors at enrollment was as follows; hypertension, 59%; myocardial infarction, 25%, cardiac arrhythmia, 47% (of which 16% had atrial fibrillation); diabetes mellitus, 29%, and transient ischemic attack, 18%. Of course many patients had multiple risk factors. We analyzed whether the presence of a risk factor at enrollment and its quality of control during follow-up affected stroke recurrence frequency and the mortality rates. These results will be reported in future papers.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum immunoglobulin changes in relation to tonsil and adenoid surgery.

In the course of clinical trials of tonsillectomy, adenoidectomy, and adenotonsillectomy, we measured serum levels of immunoglobulins G, A, and M by rate nephelometry in 268 subjects at baseline and at intervals after receipt or nonreceipt of surgery. Up to 30 months after baseline we observed a consistent pattern of change only in levels of immunoglobulin G, decreases in which tended to occur more commonly and be of greater magnitude in subjects who received tonsillectomy or adenotonsillectomy than in corresponding control subjects. However, in both surgical and control subjects the subsequent incidence of throat infection showed no relationship to either contemporaneous immunoglobulin levels or changes from baseline levels. A decline in serum immunoglobulins following tonsillectomy appears not to be a risk factor for developing throat infection, and may reflect a reduction in antigenic stimulation.

Asthma. A role for IVIG therapy?

Asthma is a multifactorial, reversible, obstructive lung disease that manifests airway inflammation as well as airway hyperreactivity. In addition to IgE-mediated respiratory reactions, the pathophysiology of asthma can be triggered by both viral respiratory and bacterial sinopulmonary infections. Even though most asthma patients do not manifest undue susceptibility to infection, a subset of asthma patients with recurrent sinopulmonary as well as upper-respiratory infections may have an associated immune deficiency syndrome. In a subset of these patients, deficiencies of serum IgG subclasses have also been described in the presence of low-normal or normal serum IgG and also deficient serum IgA. In addition to the usual asthma therapy with beta 2 agonist and theophylline bronchodilators as well as cromolyn and steroids, many of these immunodeficiency patients will benefit from iv gamma-globulin therapy. However, we suggest that an inability to synthesize specific serum antibody to injected vaccines or immunogens be a prerequisite before initiating iv gamma-globulin therapy. The clinician should not rely on serum IgG subclass levels alone as a criterion for initiation of passive immune globulin therapy. There may be another cohort of asthma patients who could benefit from iv gamma-globulin therapy. In a small open-label pilot study severe steroid-dependent asthma patients who were not immunodeficient and did not have undue susceptibility to infection were treated with iv gamma-globulin with a very large dosage protocol of 2000 mg/kg monthly.(ABSTRACT TRUNCATED AT 250 WORDS)