Aspects of truth: statistics, bias, and confounding.
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Biomedical subjects
Publications and source records attributed to S Sheps.
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The possibility that peak inspiratory pressure requirements or the arterial:alveolar oxygen ratio can predict the clinical outcome in infants weighing less than 750 g at birth was explored in a consecutive series. Nine of 10 infants (90%) with a peak inspiratory pressure requirement of more than 18 cm H2O at 48 hours or more than 16 cm H2O at 72 hours from age subsequently died later of respiratory causes (defined as death after 72 hours of pulmonary interstitial emphysema, bronchopulmonary dysplasia, or cor pulmonale). Twenty of 21 remaining infants (95%) survived until discharge. Using these data a 95th centile for peak inspiratory pressure requirement during the first 72 hours of life was constructed. The potential value of this centile in predicting later death of respiratory causes was examined in a separate series. Twelve of 15 infants (80%) whose peak inspiratory pressure requirements remained below the 95th centile, or were not ventilated (n = 6), survived. In contrast, 11 of 12 (92%) infants whose requirements crossed the 95th centile died later of respiratory causes. The infants who died had more radiological changes and higher mean arterial carbon dioxide pressure than survivors suggesting that the severity of the initial lung disease rather than the way that ventilation was managed determined prognosis. Peak inspiratory pressure requirement was more useful than arterial:alveolar oxygen ratio in clearly distinguishing between survivors and infants who died later of respiratory causes.
To determine whether orally administered zinc supplements could correct the abnormal humoral and cell-mediated immunity of Down syndrome, we randomly assigned 64 children with Down syndrome, aged 1 to 19 years and living at home, to receive either zinc gluconate or placebo daily for 6-month periods with crossover from one regimen to another. Control subjects were siblings and age-matched, unrelated children. Serum zinc, copper, and measures of immune system competence were tested at 3- or 6-month intervals. Parents kept daily logs of clinical symptoms such as cough and diarrhea and of physician visits. Mean serum zinc concentrations increased to about 150% of baseline during zinc supplementation, but we found no effect on serum levels of copper, immunoglobulins, or complement; on lymphocyte number or subset distribution; or on in vitro response to mitogens. Children with Down syndrome who were receiving zinc had a trend toward fewer days or episodes of cough and fever but no change in other clinical variables. Long-term, low-dose oral zinc supplementation to improve depressed immune response or to decrease infections in children with Down syndrome cannot be recommended.
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We investigated the effect of an intraoperative desmopressin acetate infusion on blood loss after cardiac operation in 60 children, by using a prospective, randomized, double-blind trial. Thirty patients received a desmopressin dose of 0.3 microgram/kg intravenously over 15 minutes at the conclusion of cardiac bypass, and 30 received a saline placebo. The two groups were comparable with respect to age, sex, cardiac lesion, presence of cyanosis, and prevalence of Down's syndrome. Results showed no significant difference in postoperative blood loss between the two groups (30.5 +/- 37.9 ml/kg in the placebo group versus 40.0 +/- 33.1 ml/kg in the desmopressin group). Postoperative bleeding time, total urine output, postinfusion hemodynamics, and postoperative coagulation studies did not differ significantly between the two groups. We conclude that postbypass desmopressin infusion does not reduce blood loss in children undergoing cardiac operations.
We studied 62 consecutive patients with progressive autonomic failure (PAF) or multiple system atrophy (MSA) (26 PAF; 36 MSA). Patients were well matched in age (67 vs 66 years), duration (39 vs 36 months), and severity of autonomic failure (median values for PAF and MSA). Peripheral somatic neuropathy occurred in 2 patients with PAF and 7 patients with MSA. Postganglionic sudomotor and vasomotor functions were studied using the quantitative sudomotor axon reflex test and supine plasma norepinephrine. The extent and severity of autonomic failure were assessed by the thermoregulatory sweat test, by heart rate responses to deep breathing and the Valsalva maneuver, and by blood pressure recordings. Severe and widespread anhidrosis was found in both PAF and MSA patients. Postganglionic sudomotor failure occurred at the forearm in 50% each of PAF and MSA patients and at the foot in 69% and 66% of PAF and MSA patients, respectively. However, postganglionic sudomotor function was preserved in some patients with anhidrosis on thermoregulatory sweat test, indicating a preganglionic lesion. Vagal abnormalities were found in 77% and 81% of PAF and MSA patients. Supine plasma free norepinephrine values were significantly reduced in PAF (p less than 0.001), but not in MSA, patients. Standing plasma norepinephrine values were reduced in both PAF (p less than 0.001) and MSA (p less than 0.001) patients. We conclude the following: (1) PAF is characterized by combined postganglionic sudomotor and adrenergic failure. (2) MSA is associated with a similar frequency of postganglionic sudomotor failure, but postganglionic adrenergic denervation was uncommon. (3) Preganglionic neuron is also involved in both disorders, but more severely in MSA. (4) Somatic neuropathy may occur.
Abnormalities of humoral and cell-mediated immunity have been described in Down syndrome but reported findings have been inconsistent. Confounding factors have included age, institutional versus home life, hepatitis B antigenemia, and zinc deficiency. To clarify this problem, we studied 64 children with Down syndrome (DS) compared with an age-matched control group. All children had always lived at home. All the DS children were negative for hepatitis B surface antigen. Serum zinc concentration in the DS group was on average 12 micrograms/dl lower than age-matched control children. They also had significantly lower levels of immunoglobulin M, total lymphocyte count, T and B lymphocytes, and T helper and suppressor cells. In vitro lymphocyte response to phytohemagglutinin and concanavalin A was significantly reduced at all ages in the DS group. Lymphocyte response to pokeweed mitogen increased with age in control children but decreased in the DS children. By 18 yr, the mean response for DS was 60000 cpm lower than controls. The DS group had significantly higher concentrations of immunoglobulins A and G than controls and the difference increased with age. Complement fractions C3 and C4 were also higher in the DS group at all ages. The number of HNK-1 positive cells was higher in the DS group than controls at all ages. When hepatitis and institutionalization are excluded as confounding factors, DS children still differ in both humoral and cell-mediated immunity from an age-matched control group.
Pertussis, though uncommon in people older than 9 years, does occur (in girls and women primarily) and should be considered in the differential diagnosis of persistent cough. Earlier this year in British Columbia a 12-year-old girl contracted the disease, even though she had been fully vaccinated against it at the appropriate ages. The source of her infection was unknown. The clinical picture was classic except that the girl experienced intense headaches, lasting up to an hour, after the episodes of paroxysmal coughing. Canadian physicians and public health practitioners should encourage vaccination against pertussis.
This study reports an evaluation of care given at an urban multidisciplinary community family practice clinic. By means of an "indicator-condition" approach, the criteria and rating system developed for the Burlington Randomized Controlled Trial (BRCT) were applied to 103 randomly selected charts demonstrating 124 episodes of care given for seven specific "conditions": otitis media, hypertension, prenatal care, care of the newborn up to the age of 12 months, immunization up to the age of 24 months, depression and urinary tract infection. Overall, 83 (67%) of the episodes of care studied were rated adequate or superior. The proportion of such episodes varied from 33% for hypertension to 81% for care of the newborn. No statistically significant differences were found between these results and those of the BRCT. A total of 48 instances of inadequate care were noted, of which 21 (44%) were omissions in patient management. Inadequate preventive care and care of chronic diseases was more common than inadequate care of acute infectious diseases. The method of primary care assessment used was found to be both practical and inexpensive.
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Three reflectance meters available in Canada for glucose self monitoring were assessed for accuracy and reliability in determining capillary blood glucose compared with venous serum glucose assayed by the laboratory hexokinase method and to capillary whole blood glucose determined by the glucose-oxidase method on a YSI (Yellow Springs Instrument, Yellow Springs, Ohio). The readings with all three meters correlated with serum glucose rather than with whole blood glucose. The Ames Glucometer (Ames Division, Miles Laboratories, Rexdale, Ontario, Canada) was found to have the best predictive value over the full range of serum glucoses from 30 to 399 mg/dl. The Lifescan Glucoscan (Lifescan Inc., Mountainview, California), although reading satisfactorily in the range 30-180 mg/dl, significantly underestimated the capillary glucose at values greater than 180 mg/dl. The Hypoguard Hypocount B (Hypoguard Ltd., Suffolk, England) on the other hand read consistently high in the range 30-99 mg/dl but read satisfactorily over the range 100-399 mg/dl. All three methods, however, had inherent limitations that must be taken into account in their clinical application.
We undertook a pilot study in order to obtain baseline health information on the Hispanic American Community in Vancouver and to evaluate the feasibility of research in this community. We used the Interviewer Administered Questionnaire and the Lifestyle and Your Health Questionnaire from the Canada Health Survey [CHS]. Questionnaires were translated into Spanish and back into English. Descriptive analyses were similar to the CHS and focussed on health services utilization, lifestyle practices and psychological parameters. 43.3% of males and 12% of females did not have any medical consultation in the previous 12 months; 100% of respondents stated that high cost did not allow regular dental care; 23.3% of males and 28.6% of females experienced anxiety and depression; 26.2% of females did not known how to do breast self-examination. Significant potential health problems exist in this community particularly related to stress, lack of preventive behaviour and low utilization rates. Further research in this community is possible, but hampered primarily by a reluctance to participate because of concerns regarding privacy and immigration status.
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