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Biomedical subjects

V Farewell

Publications and source records attributed to V Farewell.

At least 19 recordsLinked to original sources
PubMed2000

Randomized trials versus observational studies in adolescent pregnancy prevention.

The objective of this study is to compare the results of randomized trials and observational studies of interventions to prevent adolescent pregnancy. We identified published and unpublished reports through computerized searches of CATLINE, CINAHL, CONFERENCE PAPERS INDEX, DISSERTATION ABSTRACTS ONLINE, EMBASE, ERIC, MEDLINE, NTIS, POPLINE, PsycINFO, and SOCIOLOGICAL ABSTRACTS; manual searches of eight relevant journals; reference lists from primary articles; and contact with content experts. We included randomized trials and observational studies that evaluated the impact of primary prevention interventions including sex education classes, school-based clinics, free-standing clinics, physician/nurse practitioner practice-based service, improved access, and community-based programs on four outcomes: sexual intercourse, birth control use, responsible sexual behavior, or pregnancy in adolescents. One investigator abstracted the data and a second conducted a detailed review of the abstraction. We identified 13 randomized trials and 17 observational studies. We generated estimates of the impact of the interventions separately for males and females for all four outcomes for both observational studies and randomized trials. For six of the eight outcomes the summary odds ratios for the observational studies showed a significant intervention benefit (P<0.05) while the randomized trials did not show a benefit for any outcome in either females or males. The difference between the results of the observational studies and randomized trials was statistically significant in two of the eight outcomes (P<0.05 for initiation of intercourse and pregnancy in females). Observational studies yield systematically greater estimates of treatment effects than randomized trials of adolescent pregnancy prevention interventions. Public policy or individual patient treatment decisions should be based on observational studies only when randomized trials are unavailable and only with careful consideration of possible biases.

Adolescent↗
PubMed2000

Methodological issues in randomized controlled trials.

There is increasing emphasis on the need to practise evidence-based medicine and the strongest evidence comes from well designed and well-conducted randomized controlled trials. Every component is important for the success of a clinical trial; if the design or sample size is inappropriate, then the results of the study will be unreliable, however well the study is conducted. Conversely a well-designed study may founder because of poor outcome measurement or unacceptably high subject loss. The advantages of a well-designed trial apply equally to studies with short term outcomes and to those requiring long-term follow up. This paper therefore focuses on general methodological issues with a discussion, where appropriate, of the special considerations associated with long-term follow-up. This emphasis is motivated by the belief that a trial with methodological weaknesses is both a waste of resources and unethical. Anyone planning to undertake a randomized controlled trial should consult a more comprehensive text [1-4]. Here, some selected issues are highlighted with the choice of topics reflecting the experience and interests of the authors.

Humans↗
PubMed1999

The association of socio-economic status, race, psychosocial factors and outcome in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the relationship between socio-economic status, race, psychosocial factors and outcome in patients with systemic lupus erythematosus (SLE). METHODS: One hundred and ninety-five patients with SLE were studied at two centres in the UK (London and Birmingham). Information about sociodemographics, income, employment status, social support and satisfaction with care was obtained. Outcomes were assessed by end-organ damage, disease activity and employment status. RESULTS: Non-Caucasian race, longer disease duration, higher disease activity and lower level of education were associated with more organ damage in SLE. More satisfaction with access to care and interpersonal aspects of care, but less satisfaction with time spent with doctors, were also associated with more damage. Very long disease duration was associated with higher disease activity. Patients with higher disease activity, lower level of education and from the Birmingham centre were more likely not to be working due to their lupus. CONCLUSION: Race and socio-economic status, as well as clinical and psychosocial factors, determine outcome in SLE.

Adult↗
PubMed1998

Correlation of 9G4 idiotope with disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: To compare the levels of the 9G4 idiotope (9G4 Id) in systemic lupus erythematosus (SLE) patients with a detailed disease activity index, the British Isles Lupus Assessment Group (BILAG) index, and serological parameters of disease activity by ds DNA antibody levels and serum C3 concentrations. METHODS: In a cross sectional analysis serum samples from 190 patients with SLE were studied and a further 55 serial bleeds from 14 patients. An enzyme linked immunosorbent assay was used to measure the 9G4 Id, and anti dsDNA and antimyeloperoxidase (MPO) antibodies. The C3 levels were measured by laser nephelometer. RESULTS: Seventy six of 190 (40%) of the patients tested had raised 9G4 Id levels. In the cross sectional study 9G4 Id levels were found to correlate with disease activity in the BILAG cardiovascular/respiratory renal, and haematological systems and with global BILAG score (p < 0.01). In the serial bleeds 9G4 Id levels correlated with anti-dsDNA antibody and C3 levels, but not with anti-MPO antibodies. No correlations were found with treatment. In six cases the 9G4 Id levels correlated well with global BILAG scores and dsDNA antibody levels. In four cases the BILAG global and 9G4 Id levels alone correlated well. CONCLUSIONS: Raised levels of the 9G4 Id are present in a substantial proportion of serum samples from patients with lupus, correlate with various aspects of disease activity in SLE. The Id is detectable on anti-dsDNA antibodies, though it must also be present on other immunoglobulins whose specificities remain unknown.

Antibodies, Antinuclear↗
PubMed1997

Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss.

BACKGROUND: Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss. METHODS: We screened 773 nonpregnant women who had the unexplained loss of at least two fetuses for antinuclear, anti-DNA, antilymphocyte, and anticardiolipin antibodies and for the lupus anticoagulant. Of 385 women with at least one autoantibody, 202 who later became pregnant were randomly assigned in equal numbers to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy. The women were stratified according to age (18 to 34 years or 35 to 39 years) and the week of gestation at which the previous fetal losses had occurred (< or = 12 or > 12 weeks). The primary outcome measure was a successful pregnancy. RESULTS: Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02). CONCLUSIONS: Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.

Abortion, Habitual↗
PubMed1997

Enhancing sensitivity to facial expression of pain.

Clinicians have long appreciated the information communicated by a patient's facial expression. Advances in the measurement of facial movements, using the Facial Action Coding System (FACS) have allowed for identification of a universal expression of pain, which is primarily encoded in four facial movements. While the FACS provides a rigorous assessment of facial expression, the time required to learn the system and to analyze the facial expression by use of slow motion video recording, makes its use impractical in the clinical setting. The purpose of this research was to examine whether exposure to a brief training procedure, based on orienting subjects to the four facial movements, would increase sensitivity to pain communicated by facial expression. Seventy-five occupational and physical therapy student volunteers were randomly assigned to training or control groups. The trained group was exposed to a 30-min training session. Both groups were then asked to rate a videotape of patients undergoing assessment of a painful shoulder and rate the amount of discomfort the patients appeared to be experiencing. Analyses indicated that the trained group was significantly more sensitive to subtle facial movements associated with low levels of pain. Relative to the patients' ratings, there was a tendency for raters to underestimate pain particularly when these were at a high level. The findings lend hope to the feasibility of developing a tool which would be clinically useful though this may be more difficult for observers judging more complex facial expressions associated with high levels of pain.

Adult↗
PubMed1996

Determinants of mortality from cystic fibrosis in Canada, 1970-1989.

The frequency, prevalence, and mortality patterns of cystic fibrosis were analyzed in 3,795 patients documented in the Canadian Patient Data Registry in 1970-1989. Cystic fibrosis frequency in the 1970-1979 birth cohort was virtually identical to the commonly quoted 1 in 2,500. In 1985-1989, median survival age was 36.7 years for males and 27.8 years for females, compared with 26.6 and 19.7, respectively, in 1970-1974. However, there were significant regional differences when Canada was divided into the four regions, East, Quebec, Ontario, and West. In Quebec, patients were younger at diagnosis and until recently had greater mortality than patients in other regions, which suggests more severe disease; dramatically improved survival in the 1980s coincided with a change from a restricted fat diet to a high fat diet. Improved survival in Ontario in the 1970s accompanied this change in dietary therapy, which may also account for good survival throughout the study period in the East. The West showed gradually improving survival, similar to that reported in other parts of the world. Proportional hazards analysis showed pulmonary function to be the best predictor of survival. Poorer survival in females was associated with poorer weight, but the interrelation of declining pulmonary function, weight maintenance, sex, and mortality requires further study. The effect of pulmonary colonization with Pseudomonas aeruginosa was confounded with degree of pulmonary dysfunction, but colonization with Burkholderia cepacia (previously Pseudomonas cepacia) was associated with increased mortality at all levels of pulmonary function.

Adolescent↗
PubMed1996

Secretory phospholipase A2 as an index of disease activity in rheumatoid arthritis. Prospective double blind study of 212 patients.

OBJECTIVE: A limited retrospective study of patients with rheumatoid arthritis (RA) found that serum secreted phospholipase A2 (sPLA2) activity correlates with disease activity (J Rheumatol 1988; 15:1351-5). To assess the strength of this relationship we investigated prospectively 212 patients with RA using a double blind approach. METHODS: 212 patients who fulfilled the 1987 ACR criteria for RA had 420 clinical and laboratory assessments. 65 patients were assessed on one occasion and 147 on multiple occasions (a mean of 2.41 visits/patient). sPLA2 was tested by an independent investigator. RESULTS: sPLA2 activity assessed as a dichotomous variable (less or more than mean +/- 2 SD) correlated highly (p < 0.005) with Lansbury index, number of effusions, number of damaged joints, erythrocyte sedimentation rate (ESR), platelet count, and low hemoglobin. Univariate and multivariate regression analyses showed significant correlations with Lansbury index, active and effused joints, hemoglobin, platelet count, and ESR. The best correlation was observed in a multivariate model that included Lansbury index, ESR, and platelet count (r = 0.60). Analysis of longitudinal changes in sPLA2 activity in 147 patients assessed more than once showed that sPLA2 correlates significantly with Lansbury index, active and effused joints, and hemoglobin. CONCLUSION: Serum sPLA2 activity correlates significantly with Lansbury index, active and effused joints, ESR, platelet court, and hemoglobin. Thus, sPLA2 can serve as an index of disease activity in RA.

Adolescent↗
PubMed1995

Anticardiolipin antibodies in systemic lupus erythematosus: clinical and laboratory correlations.

PURPOSE: To examine the link between anticardiolipin antibodies and the features of antiphospholipid syndrome in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: In this prospective cohort study conducted in a single center, 390 SLE patients were followed up between June 1991 and 1994. At each assessment, a complete history, physical examination, and laboratory evaluation (including measurement of anticardiolipin antibodies) were performed according to a standard protocol. RESULTS: Forty-seven percent of the patients had an elevated level of anticardiolipin antibodies. In the univariate analysis, elevated anticardiolipin antibody levels were found to correlate with thrombocytopenia (P = 0.006), prolonged activated partial thromboplastin time (aPTT) (P = 0.003), and positive direct and indirect Coombs' test result's (P < 0.001). No correlation was identified with any of the clinical features of antiphospholipid syndrome. In the multivariate analysis, anticardiolipin antibodies remained highly associated with thrombocytopenia (odds ratio [OR] 4.05, P = 0.02), positive direct Coombs' test (OR 2.31, P < 0.001), and prolonged aPTT (OR 1.73, P = 0.03). In the multivariate model using venous/arterial thrombosis as the outcome variable, only prolonged aPTT was associated with venous/arterial thrombosis (OR 7.9, P < 0.001). None of the laboratory variables were found to correlate with fetal loss. CONCLUSIONS: The presence of anticardiolipin antibodies in patients with SLE is associated with prolonged aPTT, thrombocytopenia, and positive Coombs' test result, but not with antiphospholipid syndrome. Prolonged aPTT is strongly associated with venous/arterial thrombosis.

Adolescent↗
PubMed1991

A predictive model for the clearance of soluble phospholipase A2 during septic shock.

Circulating phospholipase A2 (PLA2) has been recognized as a mediator of cardiovascular collapse in septic shock. Proximal mediators of endotoxemia, including tumor necrosis factor and interleukin 1, induce PLA2 synthesis and release, but the factors regulating PLA2 elimination are unknown. Similarly, the kinetics of PLA2 clearance during recovery from septic shock have not been examined. An autoregressive mathematical model was developed to describe the rate of PLA2 clearance during the recovery phase of septic shock. This model (which estimates that the current day's PLA2 level is 77% of the previous day's level), accounted for 89% of the variability seen in the data. The estimated circulating half-life of soluble PLA2 in septic shock in man was 32 hours. Since elevation in serum PLA2 activity is closely associated with bacteremia or endotoxemia, a significant deviation from predicted PLA2 values may denote impending relapse.

Adult↗
PubMed1990

Reliability of measurements of active and damaged joints in psoriatic arthritis.

Our aim was to test the reliability of clinical measurements in psoriatic arthritis. The study involved clinical assessments of inflammatory activity as well as damage in 10 patients with psoriatic arthritis seen at the psoriatic arthritis clinic. Five rheumatologists examined these patients according to a latin square design. For the clinical measurements of actively inflamed joints and damaged joints there was no significant observer effect. This suggests that these are reliable measurements. There was, however, significant observer effect in the radiologic assessment, and further refinement of the measurement is required.

Arthritis, Psoriatic↗
PubMed1988

Pathogenesis of hypotension in septic shock: correlation of circulating phospholipase A2 levels with circulatory collapse.

Circulating phospholipase A2 (PLA2) has been recognized as a mediator of circulatory collapse in experimental endotoxic shock. To assess the role of serum PLA2 in septic shock in man, we determined serum PLA2 profiles in a prospective study in 12 patients with septic shock. During the hypotensive phase of sepsis, serum PLA2 levels were consistently elevated as high as 33,428 U/ml (normal range 115 +/- 12 [SE]; n = 101). In all 12 patients, PLA2 levels correlated directly with the magnitude and duration of circulatory collapse (p less than .001), with a progressive fall of serum PLA2 levels during convalescence. In contrast, serum PLA2 levels in patients with cardiogenic shock secondary to myocardial infarction remained low. In pancreatitis, PLA2 levels paralleled fluctuations of serum amylase and lipase, whereas in septic shock without pancreatic involvement, PLA2 changes were discordant with changes in pancreatic enzymes. As well, septic shock serum PLA2 failed to crossreact by radioimmunoassay with antiserum against human pancreatic PLA2. These data are consistent with an extrapancreatic source of intravascular PLA2 release during sepsis. Since endogenous serum PLA2 levels correlate directly with the magnitude of hypotension in both experimental endotoxic shock and clinical septic shock, and since parenteral administration of purified exogenous PLA2 reproduces hypotension in experimental models, we conclude that high levels of intravascular PLA2 may contribute similarly to the circulatory collapse in septic shock in man.

Adult↗
PubMed1988

Concordance of endogenous cortisol and phospholipase A2 levels in gram-negative septic shock: a prospective study.

Lipocortins, a group of corticosteroid-induced phospholipase-inhibitory proteins, are thought to play a prominent role in the mediation of the anti-inflammatory effects of steroids. The synthesis and release of these proteins may represent a major endogenous mechanism of regulation of extracellular phospholipase A2 (PLA2) activity. Because soluble PLA2 activity has been associated with circulatory collapse in hyperphospholipasemic conditions, such as septic shock and pancreatitis, we examined the relationship between circulating PLA2 activity and adrenocortical function. In a prospective study of 10 episodes of septic shock, serum PLA2 and cortisol levels correlated significantly in all survivors (p less than 0.0001), whereas such a correlation was absent in all nonsurvivors (p less than 0.07). No significant correlation of cortisol and adrenocorticotropic hormone (ACTH), or PLA2 and ACTH, was found in any patient, suggesting that the stimulus for cortisol release arises from outside the hypothalamic-pituitary axis. These data suggest that, in human beings, the regulation of soluble PLA2 activity may be mediated by adrenocortical hormones, perhaps through the intermediary action of lipocortins.

Adrenocorticotropic Hormone↗
PubMed1988

Early function as the principal correlate of graft survival. A multivariate analysis of 200 cadaveric renal transplants treated with a protocol incorporating antilymphocyte globulin and cyclosporine.

We examined the factors determining graft survival in 200 consecutive cadaveric renal transplants managed on a quadruple-therapy protocol: Minnesota antilymphoblast globulin, cyclosporine, azathioprine, and low-dose prednisone. Perioperative central venous pressure monitoring and volume expansion were emphasized. To avoid CsA nephrotoxicity in the early posttransplant period, patients were treated with ALG until renal function was established (a mean of 7 days). Therapeutic CsA levels were achieved before ALG was discontinued. Azathioprine was used to supplement CsA in patients with nephrotoxicity or rejection. Twelve-month graft survival was 85% (first transplants 86%, retransplants 79%), with patient survival of 95%. ALG was not associated with excessive clinical cytomegalovirus infections, which occurred in 5% of patients, or with malignancy. When 3 technical failures were excluded, an analysis of numerous factors in the pretransplant and peritransplant period revealed that the strongest correlate of one-year graft survival was early renal function. Grafts with delayed function (DF) had 75% survival, compared with 91% for grafts with good early function (EF). A multivariate analysis confirmed this association: the relative risk of graft loss was increased 2.86 times for DF compared with EF. The mechanism of the deleterious effect of DF was apparently multifactorial: the DF group, by definition, contained all the kidneys that never functioned, but some risk also persisted in kidneys that achieved function. One reason for this may be that DF kidneys that achieved function had higher mean serum creatinine values at 1 month: elevated serum creatinine values at 1 month were strongly associated with increased risk of graft loss regardless of initial function. There was also a higher number of rejection episodes diagnosed in the DF group. These observations suggest that early renal function is a major determinant of graft outcome and should be a target for efforts to further improve renal graft survival.

Antilymphocyte Serum↗
PubMed1986

Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia.

We treated 93 patients who had acute nonlymphoblastic leukemia in the first remission or chronic myelocytic leukemia in the chronic phase (median age, 30 years) with high-dose cyclophosphamide and fractionated total-body irradiation, followed by infusion of marrow from an HLA-identical sibling. To evaluate postgrafting prophylaxis for graft versus host disease, we studied these patients in a sequential, prospective, randomized trial that compared the effect of a combination of methotrexate and cyclosporine (n = 43) with that of cyclosporine alone (n = 50). All patients had evidence of sustained engraftment. A significant reduction in the cumulative incidence of grades II to IV acute graft versus host disease was observed in the patients who received both methotrexate and cyclosporine (33 percent), as compared with those who were given cyclosporine alone (54 percent) (P = 0.014). Seven patients who received cyclosporine alone acquired grade IV acute graft versus host disease, as compared with none who received both methotrexate and cyclosporine. Thirty-five of the 43 patients given both methotrexate and cyclosporine and 31 of the 50 patients given cyclosporine are alive as of this writing, at 4 months to 2 years (median, 15 months); the actuarial survival rates in the two groups at 1.5 years were 80 percent and 55 percent, respectively (P = 0.042). We conclude that the combination of methotrexate and cyclosporine is superior to cyclosporine alone in the prevention of acute graft versus host disease after marrow transplantation for leukemia, and that this therapy may have a beneficial effect on long-term survival.

Acute Disease↗
PubMed1986

Marrow transplantation for severe aplastic anemia: methotrexate alone compared with a combination of methotrexate and cyclosporine for prevention of acute graft-versus-host disease.

Forty-six patients with severe aplastic anemia (median age, 23 years) were treated with high-dose cyclophosphamide followed by infusion of marrow from an HLA-identical family member. To evaluate postgrafting prophylaxis for graft-v-host disease (GVHD), they were entered into a prospective randomized trial comparing the effect of a combination of methotrexate and cyclosporine (n = 22) to that of methotrexate alone (n = 24). Forty-four of the forty-six patients had evidence of sustained marrow engraftment. Only one patient in each of the two study groups showed graft rejection. A significant reduction in the cumulative incidence of grades II to IV acute GVHD was seen in patients given methotrexate/cyclosporine (18%) compared with those given methotrexate alone (53%) (P = .012). In three patients given methotrexate alone, grade III developed, and in six, grade IV acute GVHD developed, compared with none given methotrexate/cyclosporine. Eighteen of the 22 patients given methotrexate/cyclosporine and 15 of the 24 given methotrexate alone are alive between 5.5 and 44.5 months (median, 18 months), with actuarial survival rates at 2 years of 82% and 60%, respectively (P = .062). The incidence of fatal infections was higher in patients given methotrexate alone, whereas there are as yet no significant differences in the incidence of chronic GVHD. We conclude that methotrexate/cyclosporine treatment resulted in a significant decrease in the incidence and severity of acute GVHD in patients who received transplants for severe aplastic anemia and thus an improvement in survival.

Acute Disease↗