Michael Grace

Hazard ratio in clinical trials

Time-to-event curves analyzed by Cox proportional hazards regression are commonly used to describe the outcome of drug studies. This methodology has the advantage of using all available information, including patients who fail to complete the trial, such as in cancer chemotherapy or human immunodeficiency virus antiviral treatment studies. The goal of treatment in such studies may be to prevent the development of a complication, for example, Pneumocystis carinii pneumonia, and to describe the likelihood of this complications developing in the treatment group compared to the control group. The hazard ratio describes the relative risk of the complication based on comparison of event rates.

Spine Trauma and Associated Injuries

A longitudinal, prospectively gathered data base of spine trauma has been developed. A review of 508 consecutive hospital admissions identified the presence of associated injuries in 240 (47%) individuals, most frequently involving head (26%), chest (24%), or long bones (23%). Twenty-two per cent had one associated injury, 15% had two, and 10% had three or more. Most spine fractures involved the lower cervical (29%) or thoracolumbar junction (21%). Comparisons of presence or absence of associated injuries and spine fracture level showed significant differences (p less than 0.001). Eighty-two per cent of thoracic fractures and 72% of lumbar fractures had associated injuries compared to 28% of lower cervical spine fractures. While there was no significant relationship between type of associated injury and spine fracture level, those with associated injuries were less likely to have a neural deficit (p less than 0.05). After hospital admission, there were seven deaths. Early assessment and transport of spine trauma victims must be carried out with appropriate management of associated injuries. Conversely, multiple trauma victims must be handled with due regard for a possible spine fracture. The value of spinal units with specially trained personnel is emphasized.

Quality of life measures before and one year after admission to an intensive care unit.

OBJECTIVE To assess outcome of patients admitted to an intensive care unit (ICU), using a prospective 1-yr follow-up, with special emphasis on various quality of life measures before and after admission to the ICU. DESIGN Prospective comparison of quality of life before and 1 yr after admission to the ICU. SETTING Eleven-bed adult medical/surgical ICU. PATIENTS All patients admitted to the ICU over a 1-yr period were eligible for inclusion in this study. Repeat admissions were enrolled only on first admission. Patients < 17 yrs of age and those patients who died within 24 hrs of admission were excluded. INTERVENTIONS Quality of life measures were collected before and 6 and 12 months after ICU admission. MEASUREMENTS AND MAIN RESULTS The following data were collected: duration of ICU and hospital stay; ICU, hospital, 6- and 12-month mortality; quality of life (level of activity, activities of daily living, perceived health, support, and outlook on life) and place of residence at baseline and 12 months after ICU admission. There were 504 patients who met the study criteria; age 55 +/- 20 yrs (median 59), 229 female and 275 male. Mean ICU length of stay was 4.3 +/- 7.4 days. Hospital length of stay was 31 +/- 41 days. Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 14 +/- 7. Cumulative mortality: ICU 5.4%, hospital 13.5%, 6 month 20.6%, and 12 month 25%. One year quality of life questionnaires were completed for 293 patients. Relative to baseline, there was a decrease in the level of activity and activities of daily living at 12 months (p < .01). Perceived health status increased over the year for patients > or = 75 yrs of age (p < .01). There was no difference in the level of support from family or friends, or outlook on life, at 12 months. At 1 yr, 262 (89%) patients were living at home. CONCLUSION Patients admitted to intensive care tend to have a decrease in the level of activity and activities of daily living 1 yr after their ICU stay, although in the very elderly, perceived health status increases. As well, the majority (89%) of patients return home.

One-year outcome of elderly and young patients admitted to intensive care units

ObjectiveTo compare the outcome of patients over and under age 65 admitted to two intensive care units (ICUs). DesignProspective, two-center study. Convenience sample of all admissions to two adult ICUs for a 1-yr period, with a 1-yr follow-up. SettingAdult multidisciplinary closed ICUs. PatientsAll patients (n = 1,040) admitted to two ICUs during a 1-yr period were entered into the study, except patients with self-induced poisoning. Of these patients, 145 patients were lost to follow-up. InterventionsAdmission statistics on all patients included demographic, case mix, and severity data. Variables associated with intensive care unit outcomes at discharge (length of stay, mortality) and at 1 yr from admission (mortality, functional capacity, health attitudes) were analyzed. Vital status was confirmed from both Alberta Vital Statistics and Alberta Health. Follow-up interviews were conducted with all available survivors. ResultsThe elderly group (>65yrs) comprised 46% of patients studied. Both age groups (>65 yrs and <65 yrs) had comparable demographics and illness severity measures. Although ICU and 1-yr mortality rates differed between groups (16% of >65 yrs vs. 12.9% of <65 yrs ICU mortality and 49% of ≥65 yrs vs. 31% of <65 yrs 1-yr mortality), age was not a major contributor to the variance in outcome. At 1 yr, 65% of patients admitted to the study were alive. Follow-up interviews were conducted with 75% of survivors. Assessment of activities of daily living showed that the elderly patients were similar to younger patients. The elderly demonstrated more positive health attitudes than younger survivors. Functional capacity was significantly associated with health attitudes of younger patients, but not for older survivors. ConclusionsAge does not have an important impact on outcome from critical illness, which is most strongly predicted by severity of illness, length of stay, prior ICU admission and respiratory failure. Satisfaction with personal health should not be inferred from the functional status of elderly survivors of intensive care. (Crit Care Med 1993; 21:687–691).

Treatment of intraventricular hemorrhage with tissue plasminogen activator.

The patients with intraventricular hemorrhage (IVH) were treated with recombinant tissue plasminogen activator (rt-PA) injected directly into the lateral ventricles, followed by ventricular drainage. All had a decreased level of consciousness before treatment (Glasgow Coma Scale score 10 +/- 3.4). A total dose between 2 and 12 mg of rt-PA (6.4 +/- 3.3) was administered. For eight patients with aneurysmal IVH, treatment with rt-PA began with two patients the same day as the aneurysm clipping, and the day after with six patients. For a patient with an excision of a ruptured arteriovenous malformation and a patient with IVH resulting from a lateral ventricular catheterization during posterior fossa tumor surgery, treatment with rt-PA started 24 hours after surgery. After an injection of rt-PA, the ventricular drain was closed for 1 hour, followed by alternate-hourly drainage and intracranial pressure (ICP) monitoring. Five patients received a second injection of rt-PA on the second postoperative day, and one patient received a third dose on the third day. Among the eight patients given rt-PA the day after surgery, the volume of external cerebrospinal fluid (CSF) drainage for 24 +/- 8 hours before treatment was 61 +/- 57 ml, and the mean ICP was 22 +/- 5 mm Hg during this same time. Younger age and poorer neurological condition correlated with higher ICP before treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-four hour energy expenditure in critically ill patients.

Resting energy expenditure (EE) is often used as the basis of nutritional support for critically ill patients but whether resting EE is representative of total daily EE is not known. EE was measured for 24 h in ten mechanically ventilated, critcally ill patients (average Acute Physiology and Chronic Health Evaluation II score 23) to determine EE, resting EE, and the energy expended during various ICU activities. Although activities, such as weighing the patient on a sling-type bed scale, repositioning, and chest physiotherapy resulted in dramatic EE increases above resting levels (36%, 31%, and 20%, respectively), the actual contribution of these activities to total EE was small (1.1%, 2.1%, and 3.6%, respectively). The mean measured resting EE was 47.3 ± 22.3% above mean predicted EE based on the Harris and Benedict equation, and the mean total 24-h EE was 6.9 ± 2.6(SD)% above the mean measured resting EE. In this group of mechanically ventilated, critically ill patients, an activity factor of no greater than 10% above resting EE is appropriate.

A trial of the 21-aminosteroid U74006F in a primate model of chronic cerebral vasospasm

The efficacy of U74006F in the prophylaxis of chronic cerebral vasospasm (VSP) was evaluated in a randomized, double-blind, placebo-controlled trial. Forty cynomolgus monkeys were divided by restricted randomization into 2 treatment groups of 20. Five animals from each treatment group were randomized into subgroups 1 and 2. The animals of subgroup 1 were studied pathologically. Brain biopsies of the animals in subgroup 2 were performed and studied with high-performance liquid chromatography (HPLC). The remaining 20 animals supplemented the number studied angiographically. Significant VSP (P less than 0.05) was detected in the majority of vessels from the clot site (right) of both treatment groups. Electron microscopy results showed positive correlation with the angiographic data. When comparing the effects of U74006F to those of the placebo at day 7, there was a significant difference (P less than 0.05) in the degree of VSP in the right extradural internal carotid and right middle cerebral arteries. This resulted from a greater degree of VSP in placebo animals. Two animals developed delayed ischemic deficits, one from each group. The infarct of the U74006F animal was smaller than the infarct in the placebo animal. Although overall changes in phosphagen levels did not reach statistical significance, HPLC analysis of the cortical biopsies did show a decrease in the ATP/ADP +/- AMP ratio of 54% in placebo animals and only 7% in animals receiving U74006F. The middle cerebral arteries of 2 animals were also studied with HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)

EFFECT OF BREAST-FEEDING ON IMMUNE RESPONSE TO BCG VACCINATION

The effect on BCG immunisation of feeding either formula or breast milk was assessed in Canadian Cree infants who were vaccinated either at birth or after 1 month of age. The response to BCG was measured in terms of lymphocyte blastogenesis stimulated by purified protein derivative of Mycobacterium tuberculosis. Breast-feeding significantly enhanced cell-mediated immune response to BCG vaccine given at birth, but had no significant effect if vaccine was given after 1 month. These findings were not related to maternal history of tuberculosis or BCG vaccination, and the feeding method did not influence lymphocyte stimulation by candida or streptococcal antigens.

Growth of microorganisms in propofol, thiopental, and a 1:1 mixture of propofol and thiopental.

To assess and compare the growth of four microorganisms in solutions of intravenous anesthetics, known quanta of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were inoculated into propofol, thiopental, a 1:1 mixture of propofol and thiopental, and normal saline. All microorganisms were taken from standard stock cultures and incubated for 24 h (48 h for C. albicans). Growth of microorganisms in each drug was compared by counting the number of colony forming units (CFUs) grown from a subculture of each inoculated anesthetic at 0, 3, 6, 12, and 24 h. The study shows that propofol strongly supports the growth of E. coli and C. albicans but is bacteriostatic toward S. aureus and weakly bactericidal toward P. aeruginosa. In contrast, both thiopental and the 1:1 mixture of propofol and thiopental behaved differently, exhibiting markedly bactericidal properties toward E. coli, S. aureus, and P. aeruginosa and a bacteriostatic effect on C. albicans. This finding supports recommendations that a strict aseptic technique should be used when handling propofol and that the contents of an ampoule should be used within 6 h of aspirating. The measured high pH of both thiopental and the 1:1 mixture of propofol and thiopental compared to propofol alone suggest pH to be a major factor in determining whether a given drug will support microbial growth. (Anesth Analg 1996;82:475-8)

Randomised double-blind placebo-controlled study on adverse effects of rubella immunisation in seronegative women

BACKGROUND The objective of our study was to investigate the association of adverse clinical musculoskeletal and neurological events in healthy postpartum women with live attenuated (RA27/3 strain) rubella-virus vaccine, and to assess the frequency of acute and recurrent arthralgia and arthritis and associations with acute and recurrent muscle pain (myalgia) and neurological manifestations (paraesthesias). METHODS We used a randomised placebo-controlled, double-blind design in a community setting. 636 women were enrolled and, after 90 women dropped out, 546 healthy women aged 18-41 years, who were rubella seronegative on routine screening were immunised parenterally with either monovalent live attenuated (RA27/3 strain) rubella vaccine (n = 270) or saline placebo (n = 276) in the postpartum period. Outcome measures were the occurrence of acute and persistent or recurrent joint manifestations (arthralgia or arthritis) at 1, 3, 6, 9, and 12 months after immunisation. Occurrence of muscle pain (myalgia), and neurological symptoms (paraesthesia) was also assessed at the same times. FINDINGS 543 women completed 1-month follow-up. 456 women completed the 12-month assessment. There were no differences at the time of immunisation between rubella vaccine and placebo groups in distribution of age, ethnic origin, parity, time between delivery and immunisation, breastfeeding history, or histories of earlier rubella vaccination or joint complaints. Results indicated a significantly higher incidence (p = 0.006; odds ratio = 1.73 [95% CI = 1.17-2.57]) of acute joint manifestations in rubella-vaccine recipients (30%) than in placebo recipients (20%). Frequency of chronic (recurrent) arthralgia or arthritis was only marginally significant (p = 0.042; 1.58 [1.01-2.45]). INTERPRETATION RA27/3 rubella vaccine given to seronegative women during the postpartum period was significantly associated with development of acute arthralgia or arthritis. Although the numbers of women assessed and length of follow-up revealed only marginally significant differences in persistent or recurrent joint manifestations between rubella vaccine and placebo recipients, it is possible that susceptible women who are given rubella vaccination may experience this outcome.