What do primary care patients think about generic drugs?

OBJECTIVE: To examine the attitude of patients towards generic drugs and prescriptions containing generic drugs as an alternative to brand-name products, with a special focus on information on patients attitude to generic drugs provided by their general practitioners (GPs). METHODS: A total of 804 patients in 31 general practices were surveyed using a self-questionnaire. The influence of age, sex, education, disease, knowledge of generic drugs, experience with generic substitution and information provided by the GP on patient attitudes towards generic drugs and substitutions were examined. RESULTS: Nearly two thirds of the patients (509/804) stated that they knew of the difference between brand-name drugs and generics; of these, one third were not satisfied with the information given by their GPs and 37% of patients expressed general skepticism towards generic drugs because of their lower price. This attitude was more frequent among those who felt that generic prescribing was "invented" to solve the financial crisis in the German health insurance system at their expense (odds ratio (OR): 6.2; 95% confidence interval: 4.0 - 9.8) and those who had not been confronted personally with a generic substitution (OR: 1.8; 1.3 3.0). Patients who had been skeptical when first confronted with a generic substitution were more frequently among those who considered inexpensive drugs to be inferior (OR: 4.5; 2.0 10.4) and they were frequently not satisfied with the information on substitution provided by their GP (OR: 2.7; 1.2 - 5.9). CONCLUSION: GPs are in an ideal position to inform their patients adequately about the equivalence of brand-name and generic drugs. However, the patient view that inexpensive drugs must be inferior may be difficult to rectify in the short term.

Use of complementary healthcare practices among chiropractors in the United States: a survey.

CONTEXT: Although chiropractic is the most commonly used complementary healthcare practice, chiropractors have not been surveyed in depth about their attitudes toward and practice of complementary and alternative therapies apart from spinal manipulation. OBJECTIVES: To examine attitudes among US chiropractors on the role of their profession in complementary healthcare and to gather data on the types of complementary healthcare practices chiropractors use. DESIGN: Descriptive, cross-sectional study using a mail-in survey. SETTING: United States. PARTICIPANTS: Random sample of US chiropractors stratified by zip code region. RESULTS: A total of 563 surveys were completed, for a response rate of 30%. Respondents were almost equally divided on their responses to the question "Do you feel that chiropractic should at the present time be termed 'complementary'?" Although many respondents (68%) believed that chiropractic was viewed as a therapeutic modality, more (82%) believed that it should be viewed as a complete system. The therapies most commonly used by respondents in their practice were acupressure (72%), massage (72%), mineral supplements (63%), and herbs (56%). CONCLUSION: The disparity between the established view of chiropractic as synonymous with spinal manipulation and the profession's view of chiropractic as a complete system indicates a need for better interprofessional communication.

Measurement of soft tissue strain in response to consecutively increased compressive and distractive loads on a friction-based test bed.

PURPOSE: To abstract the essential elements of chiropractic prone leg checking and subject them to controlled, experimental parametric testing. DESIGN: Controlled, objective, repeated-measure analysis of the dynamic response of leg positions to distractive and compressive loading conditions. SETTING: Research laboratory in a chiropractic college. PARTICIPANTS: Twenty-five compression and 30 distraction subjects, most of whom were male, asymptomatic chiropractic students. INTERVENTION: The subjects were lowered to the prone position on a table optimized to detect dynamic leg positions, with separate sliding segments supporting each leg. A trial consisted of a 2-min control run, followed by two 2-min experimental runs in which compressive or distractive loads were applied incrementally to the table-leg segments. MAIN OUTCOME MEASURE: An optoelectric system measured real-time absolute and relative leg positions. RESULTS: Right legs showed a greater average response than left legs under both distractive and compressive loads, and tended to respond more proportionately to incremental load increases. The average response to compression exceeded the response to distraction. Both legs showed a greater average response in the second half of the trials. Correlation of weights with responses was about four times greater in traction than compression. CONCLUSION: The functional short leg is confirmed as a stable clinical reality, a multitrial mean of unloaded leg positional differences. The prone leg check may be a loading procedure, albeit unmeasured, that detects non-weight-bearing, functional asymmetry in loading responses. These probably reflect differences in left-right muscle tone, joint flexibility and tissue stiffness. The relatively nonmonotonic, nonlinear quality of left leg responses is consistent with asymmetric neurological responses.

Heparin and the risk of intraventricular hemorrhage in premature infants.

OBJECTIVE: This study was carried out to determine whether the routine use of low-dose heparin in umbilical catheter infusates increases the risk of intraventricular hemorrhage or alters the coagulation profile in premature infants. METHODS: In a randomized, blinded trial, 113 infants born at less than 31 weeks' gestation were assigned to receive, in their umbilical catheter infusate, either 1 unit of heparin per milliliter (n = 55) or no heparin (n = 58). Prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and antithrombin III activity levels were determined at the start and the completion of the study. Cranial ultrasonography was performed during the first week of life. RESULTS: There was no difference in the incidence of intraventricular hemorrhage between the heparin and no heparin groups, 35.8% and 31.5%, respectively (p = 0.6). Similarly, no difference was detected in the incidence of severe intraventricular hemorrhage (grades III/IV). Prothrombin time, activated partial thromboplastin time, and fibrinogen levels were not significantly different between the two groups. However, the use of heparin was associated with a lower antithrombin III activity level. Antenatal indomethacin use was associated with a 2.9 increased risk of intraventricular hemorrhage (95% confidence interval, 1.15 to 7.17). CONCLUSION: A low dose of heparin added to umbilical catheter infusates does not increase the incidence or severity of intraventricular hemorrhage or significantly alter the coagulation profile in premature infants.

A multicenter randomized masked comparison trial of synthetic surfactant versus calf lung surfactant extract in the prevention of neonatal respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co) and a surfactant extract of calf lung lavage (Infasurf, IND #27,169, ONY, Inc) in the prevention of neonatal respiratory distress syndrome (RDS). DESIGN AND SETTING: Ten-center randomized masked comparison trial. PATIENTS: Premature infants (n = 871) <29 weeks gestational age by best obstetric estimate. INTERVENTIONS: Infants were randomly assigned to a course of treatment with Exosurf Neonatal (n = 438) or Infasurf (n = 433) at birth, and if still intubated, at 12 and 24 hours of age. Crossover treatment was allowed within 72 hours of age if severe respiratory failure (defined as two consecutive a/A PO2 ratios

A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS). METHODS: We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratios < or = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (< or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques. RESULTS: The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (< or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p < or = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p < 0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants. CONCLUSION: Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications.

Cardiopulmonary resuscitation of the newborn. An update.

The abrupt transition from intrauterine to extrauterine life represents a series of profound physiologic changes. This process puts the baby at risk for asphyxia. At birth, the newborn is, therefore, more frequently in need of resuscitation than at any other age. This article reviews the rationale for the sequence and process of neonatal resuscitation, emphasizing recent changes in recommendations.

Iatrogenic respiratory distress syndrome following elective repeat cesarean delivery.

OBJECTIVE: To determine the incidence of iatrogenic respiratory distress syndrome (RDS) following elective repeat cesarean delivery and to identify whether it was associated with departures from accepted management guidelines. METHODS: Between January 1986 and March 1991, there were 23,125 deliveries at Northwestern Memorial Hospital, of which 1207 were repeat cesarean births without labor. During this period, 18 neonates of 37 weeks' gestation or greater or 2500 g or greater who were delivered by elective repeat cesarean were admitted to the neonatal intensive care unit (NICU) for respiratory difficulties. RESULTS: Five of the 18 neonates admitted to the NICU with respiratory difficulty following elective repeat cesarean delivery met the criteria for RDS. This represents an incidence of 0.41% (five of 1207), or one case of RDS for every 241 repeat cesarean deliveries without labor. Four of the five neonates required mechanical ventilation for an average of 6.8 days. The average NICU stay was 11.2 days. Complications included pneumothorax (one) and pulmonary hemorrhage (one). Departures from accepted management guidelines included a discrepancy between ultrasound and menstrual dates (two), no confirmation of menstrual dates (one), and delivery before 39 weeks' gestation (two). CONCLUSION: Iatrogenic RDS continues to occur in the setting of elective repeat cesarean delivery and is associated with a failure to adhere to clinical protocols.

Power spectral and microvector frequency analysis of dynamic standing foot force patterns in a normal male subject.

Power spectral and microvector frequency analyses of dynamic standing foot force patterns in a normal male subject were performed using a multiple-trial experimental protocol. Power spectral analysis of eight eyes-open vs. eyes-closed 50-sec trials revealed significant power increases in the 0.14 to 0.66 Hz range with eye closure, which were repeatable in trials performed on the same subject 2 wk later. Since power spectral differences are difficult to interpret biomechanically, a (micro)vector analysis of 1/20 sec changes in proportional weight transfer was employed. This methodology was able to reveal that foot force weight transfer exhibited a distinct preferred directionality, and that the eyes-closed condition was characterized by significant increases in both the occurrence and average magnitudes of these preferred microvectors.

Analysis of dynamic standing foot force patterns in a normal male subject by characterization of microvector weight transfer sequences.

Previous foot forceplate analyses in our laboratory have shown that postural sway in a normal male subject induces net weight transfers (microvectors) which have preferred directionalities, and that eye closure is characterized by increases in both the occurrence and magnitudes of these preferred microvectors. The same data generated from 8 x 8 blocks of eyes-open and eyes-closed trials were reanalyzed to examine microvector temporal sequences (i.e., macrovectors). Macrovectors were defined by the number of successive microvectors occurring along the same general direction, (anterior, posterior, right or left). Results suggest that with eye-closure, proprioceptive systems are unable to maintain lateral sway deviations within eyes-open limits. This instability increases lateral macrovector durations while only marginally affecting sagittal macrovector durations.

Normal paraspinal tissue compliance: the reliability of a new clinical and experimental instrument.

Test-retest reliability of a hand-held tissue compliance meter was evaluated in 20 normal subjects at four paraspinal locations to determine possible effects of probe response or other sources of variability on measurements taken 10 min later at exactly the same location. If tissue compliance, as measured by this instrument, is to be used in a pre-post context to evaluate treatment effects, caution is urged, since 26% of the sites were significantly (+/- 1.96 SD) different on 10 min retest though subjects remained supine and without intervention. In addition, since 85% of these normal subjects displayed at least one paraspinal compliance asymmetry large enough to qualify as pathological by Fischer's criteria, revision of these criteria may be appropriate, at least for these paraspinal locations.

Interexaminer concordance in detecting joint-play asymmetries in the cervical spines of otherwise asymptomatic subjects.

Interexaminer concordance for motion-based palpation of the middle and lower cervical spine was investigated. The palpatory task consisted of determining whether end-range joint resistance on lateral flexion was greater on one side of a given cervical segment when compared to that of the contralateral joint. Palpators also were asked to indicate the relative magnitude of the asymmetry, when detected. All experiments were carried out using reasonably healthy, pain-free, chiropractic college students. Three series of experiments involving two pairs of practitioners and a total of 270 subjects were carried out. Interexaminer agreement rates with respect to the side of greatest fixation were not found to be significantly different from those expected by chance alone. Furthermore, this was the case regardless of whether palpators had rated the magnitude of the asymmetry as being slight, moderate or severe. These poor agreement rates did not appear to be due to significant interexaminer differences with respect to the distributions of right vs. left calls, to a preponderance of agreements occurring more on one side over the other, or to differences with respect to the distribution of severity ratings. More importantly, there appeared to be no consistent relationships between the degree of severity indicated by the first examiner and that indicated by the second, nor were there any significant correlations between right vs. left agreement rates obtained for various combinations of severity ratings.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic illusions: the reliability of random chance.

A "Monte Carlo" experiment was performed in order to determine chance concordance rates for multiple test scenarios often encountered in chiropractic diagnosis. The Monte Carlo simulation took into account the following variables: the number of tests involved in the diagnosis; the number of vertebral segments implicated by each test; the proportion of tests in agreement relative to the number of tests performed; and the segmental margin of error accepted. Random data for up to five diagnostic tests performed on 500 "patients" were computer generated and a wide variety of test scenarios analyzed. One typical analysis asked: if four diagnostic tests are performed on each patient, each test implicating on average three vertebral segments, and a plus or minus one segment error margin is accepted, what are the chance odds that any three out of the four tests will implicate the same vertebral segment? The answer, determined by simply counting how often this happened in the 500 "patients," was 89%. Many test scenarios yielded chance levels much higher than might have been expected. High probability situations as well as those test criteria yielding relatively low chance concordance rates are identified.

Concordance between galvanic skin response and spinal palpation findings in pain-free males.

The concordance between areas of paraspinal low resistance, i.e., galvanic skin response (GSR) and positive palpatory findings in pain-free male subjects was investigated. The concordance between vertebral segments implicated by GSR and by palpation was not found to be significantly different from chance concordance as determined by a t-test comparison of experimental results to randomly generated simulations, and by the application of Cohen's Kappa index of concordance to experimental data. This was true even when the locations of low resistance areas along the dorsal trunk were compared to only those vertebral palpatory findings rated as "severe." When test-retest reliability of GSR was examined, only 27% of vertebral segments implicated by GSR on initial examination were also implicated in the same subjects 4 h later. It was noted that low resistance areas detected by GSR were always punctate in nature and appeared to correspond well to known acupuncture loci. Further investigation revealed that, indeed, the GSR unit was not only effective in locating those acupuncture points that happened to be in a state of lowered resistance at the time but was also able, within about 5 sec, to decrease the resistance of any particular point not already in its lowest state of resistance to a level sufficient to generate a positive and persistent GSR reading where none had been detected previously. It is suggested that GSR may not be a reliable predictor of the location of vertebral pathology, at least as assessed by palpation in pain-free subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

An estimate of the effect of acute exsanguination on catecholamine and glucoregulatory hormone concentrations in the newborn rat.

We have determined the effect of acute exsanguination on plasma concentrations of glucose, insulin, glucagon, dopamine, epinephrine and norepinephrine in neonatal Sprague-Dawley rats. This was done by comparing concentrations of these substances in aliquots of blood obtained within 10 s of the initial bleeding to those in blood obtained over the next 50 s of the blood drawing process. Concentrations of glucose and insulin showed no change between early and late samples. Glucagon concentrations showed variable responses dependent upon the age of the animal. Concentrations were unchanged at birth, but increased 22% and 58% at 1 and 6 h of age respectively. Catecholamine concentrations increased greatly (57 to 215%) between blood aliquots regardless of age at the time of sampling. These findings indicate that hormonal responses occur during the relatively brief period of blood drawing in Sprague-Dawley rats, pointing out further limitations inherent in the use of small animals for acute metabolic and hormonal studies.

Indomethacin therapy on the first day of life in infants with very low birth weight.

To investigate the optimal timing for treatment of small premature infants, we performed a double-blind, controlled trial of indomethacin therapy on the first day of life in 104 infants weighing between 700 and 1300 gm. Infants were given indomethacin or placebo at a mean age of 15 hours. Eleven of the 56 infants given placebo developed large left-to-right shunts through a patent ductus arteriosus. In contrast, only two of the 51 infants given indomethacin developed large shunts (P less than 0.025). There were no significant differences in incidence of surgical ligation, duration of oxygen therapy, duration of endotracheal intubation, days required to regain birth weight, or incidence of complications. However, the power of the tests of significance was low because of the small number of patients. Thus, although the incidence of large left-to-right ductus shunts was decreased in the indomethacin group, morbidity was not otherwise altered for the entire group of patients, possibly because of the relatively low incidence (21%) of large shunts in the placebo group. We conclude that although treatment with indomethacin on the first day of life appears to be safe, there is little advantage to its use in centers where the incidence of large shunts through a patent ductus arteriosus is relatively low.

Effects of asphyxia at birth on postnatal glucose regulation in the rat.

We have characterized the effect of a period of asphyxia at birth, followed by recovery, upon newborn rats. Asphyxiated pups were subjected to 3 to 5% (v/v) inspired oxygen during the first 20 min of life and then maintained in room air for 6 h. Control pups were maintained in room air throughout the 6-h period. Hypoxia produced severe asphyxia as reflected by a pH of 6.76 +/- 0.05, PaCO2 of 87 +/- 3 mm Hg and PaO2 of 15.4 +/- 4 mm Hg, and by a greatly increased blood lactate/pyruvate ratio. Plasma catecholamine concentrations in asphyxiated pups were elevated (epinephrine 13,866 +/- 250 pg/ml, norepinephrine 9611 +/- 1813 pg/ml) compared to control animals (epinephrine 973 +/- 234 pg/ml, norepinephrine 774 +/- 133 pg/ml) at 20 min. Asphyxia initially increased plasma glucose concentration, and then with recovery it fell below controls. Hepatic glycogen stores did not differ between asphyxiated and control pups. Plasma insulin concentrations remained elevated during asphyxia and the usual neonatal surge of plasma glucagon was significantly delayed. Neonatal asphyxia increases catecholamines, causes lactic acidemia, and alters insulin and glucagon levels. The interactions between these variables alters the normal pattern of glucose availability during the neonatal period.