The laser step in early glaucoma.
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Biomedical subjects
Publications and source records attributed to C L Meinert.
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OBJECTIVE: --To investigate factors associated with the publication of research findings, in particular, the association between "significant" results and publication. DESIGN: --Follow-up study. SETTING: --Studies approved in 1980 or prior to 1980 by the two institutional review boards that serve The Johns Hopkins Health Institutions--one that serves the School of Medicine and Hospital and the other that serves the School of Hygiene and Public Health. POPULATION: --A total of 737 studies were followed up. RESULTS: --Of the studies for which analyses had been reported as having been performed at the time of interview, 81% from the School of Medicine and Hospital and 66% from the School of Hygiene and Public Health had been published. Publication was not associated with sample size, presence of a comparison group, or type of study (eg, observational study vs clinical trial). External funding and multiple data collection sites were positively associated with publication. There was evidence of publication bias in that for both institutional review boards there was an association between results reported to be significant and publication (adjusted odds ratio, 2.54; 95% confidence interval, 1.63 to 3.94). Contrary to popular opinion, publication bias originates primarily with investigators, not journal editors: only six of the 124 studies not published were reported to have been rejected for publication. CONCLUSION: --There is a statistically significant association between significant results and publication.
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Our efforts to identify published articles describing meta-analyses of clinical trials illustrate the need for standard terminology to facilitate retrieval. We found 119 articles describing meta-analyses and eligible for inclusion in MEDLINE, and yet when we searched MEDLINE, using strategies based on textwords and medical subject headings (MeSH), only 48% of the 119 articles were identified. Sixty-eight (57%) of the 119 articles contained at least one of the terms "meta-analysis," "pooling," or "overview" in the title or abstract. The importance of meta-analyses in the evaluation of medical treatments argues for more disciplined use of a specific term in order to facilitate identification of articles. The fact that the National Library of Medicine has started in 1989 to index articles describing meta-analyses using the MeSH META-ANALYSIS underscores this argument.
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To assess the effects of intervention in cerebral palsy, 48 infants 12 to 19 months of age, with mild to severe spastic diplegia, were randomly assigned to receive either 6 months of infant stimulation followed by 6 months of physical therapy (test group) or 12 months of neurodevelopmental physical therapy (contrast group). The infant stimulation protocol consisted of cognitive, motor, sensory, and language activities. Outcome was assessed after 12 months by using Carey Infant Temperament Questionnaire subscores (activity, rhythmicity, adaptability, approach, threshold, intensity, mood, distractibility, and persistence); Roth Mother-Child Relationship Evaluation subscores (acceptance, overprotection, overindulgence, rejection); and Home Observation for Measurement of the Environment subscores (maternal responsiveness, avoidance of restriction and punishment, organization of environment, play materials, maternal involvement, and variety of daily stimulation). Motor and cognitive outcomes suggesting advantage for the test group have been reported previously. After 12 months of intervention, mothers with infants in the contrast group showed a greater improvement in emotional and verbal responsiveness as measured by the Home Observation for Measurement of the Environment (mean score change in control group = 1.2, test group = 0.3 P less than .04). None of the 19 other measures differed significantly between treatment groups in change from baseline. This study demonstrates no short-term systematic effect on temperament, maternal-infant interaction, or home environment attributable to the inclusion of an infant stimulation curriculum in an intervention program for infants with spastic diplegia. It suggests that motor and cognitive advantages associated with infant stimulation are not mediated by measurable changes in the psychosocial variables studied.
The Hypertension Prevention Trial (HPT) was a randomized, controlled, multicenter (four clinics, four resource centers) trial designed to test the feasibility of achieving and sustaining dietary changes in the intake of calories, sodium, and potassium and to assess the effect of those changes on blood pressure in a normotensive population. The trial involved 841 men and women (plus a test cohort of 78) who, at the first baseline (BL) examination, were in the age range of 25-49 years and had diastolic blood pressure (DBP) greater than or equal to 76 but less than 100 mm Hg (average of two readings), and at the examination prior to randomization (BL 2) had DBP greater than or equal to 78 but less than 90 mm Hg (also averaged). Participants were randomly assigned to a control treatment group (no dietary counseling) or to one of four dietary treatment groups involving counseling designed to reduce calorie intake, reduce sodium intake, reduce sodium and calorie intake, and reduce sodium and increase potassium intake. Dietary counseling was provided primarily in group settings and was aimed at changing participants' shopping, cooking, and eating habits related to a designated treatment assignment. The effect of dietary counseling was measured through changes in urinary excretion of sodium and potassium, changes in body weight, and changes in reported food intake based on 24-hour food records. Blood pressure changes during the 3-year course of followup were based on measurements taken at 6-month intervals from enrollment using a random-zero sphygmomanometer. This chapter provides a general description of the design and methods of the HPT and the underlying rationale for decisions affecting the design.
Meta-analysis of clinical trials has assumed increasing importance in recent years as a means of reaching conclusions regarding the safety and efficacy of treatments evaluated in individual trials. This article discusses impediments to meta-analyses and enumerates needs that should be satisfied to enhance their usefulness. Key among the needs are improved means of identifying trials prior to publication via prospective registration of them and vocabulary and nomenclature for identifying reports of meta-analyses in the published literature.
Investigations in which statistically significant differences between treatment groups have not been observed are less likely than others to be reported in scientific journals. In clinical research, this selective suppression of "negative" results may lead to the adoption of ineffective or hazardous treatments. In an attempt to obtain information about unpublished trials in perinatal medicine, letters were sent to 42,000 obstetricians and pediatricians in 18 countries. As a result, we were notified of 395 unpublished randomized trials. Only 18 of the trials had been completed more than 2 years before the survey, a period during which at least 2300 reports of perinatal trials had been published. Of the 395 unpublished trials, 125 had ceased recruitment within the 2 years prior to the survey, 193 were actively recruiting at the time of the survey, and 59 were about to begin recruitment. It was concluded that publication bias will not be addressed successfully by attempts to obtain information about unpublished trials retrospectively. However, since the response rate to our request for details about ongoing and planned trials was good, prospective registration of trials at inception appears to be a feasible approach to reducing publication bias and its adverse consequences. An additional merit of prospective registration of clinical trials is that it should reduce unnecessary duplication (as opposed to necessary replication) in research and promote more effective collaboration.
Legislatively mandated programs for early intervention on behalf of handicapped infants often stipulate the inclusion of physical therapy as a major component of treatment for cerebral palsy. To evaluate the effects of physical therapy, we randomly assigned 48 infants (12 to 19 months of age) with mild to severe spastic diplegia to receive either 12 months of physical therapy (Group A) or 6 months of physical therapy preceded by 6 months of infant stimulation (Group B). The infant-stimulation program included motor, sensory, language, and cognitive activities of increasing complexity. Masked outcome assessment was performed after both 6 and 12 months of therapy to evaluate motor quotient, motor ability, and mental quotient. After six months, the infants in Group A had a lower mean motor quotient than those in Group B (49.1 vs. 58.1, P = 0.02) and were less likely to walk (12 vs. 35 percent, P = 0.07). These differences persisted after 12 months of therapy (47.9 vs. 63.3, P less than 0.01, and 36 vs. 73 percent, P = 0.01, respectively). We noted no significant differences between the groups in the incidence of contractures or the need for bracing or orthopedic surgery. Group A also had a lower mean mental quotient than Group B after six months of therapy (65.6 vs. 75.5, P = 0.05). The routine use of physical therapy in infants with spastic diplegia offered no short-term advantage over infant stimulation. Because of the limited scope of the trial, our conclusions favoring infant stimulation are preliminary. The results suggest that further study of the effects of both physical therapy and infant stimulation is indicated.
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Despite their long history, the number that are in operation now, and the current level of expenditures on them, clinical trials have not been the focus of sufficient methodologic research. The paucity of metholologic explorations is further aggravated by the constraints on communications regarding methodology. Those individuals working in the area of clinical trials need to establish some professional identity with the field. Methodology in the areas of design and management of clinical trials needs to be stimulated, perhaps through special requests for applications (RFAs) and requests for proposals (RFPs). Communications could be improved by the establishments of a professional society, the development of an appropriate journal, and establishment of national training and information centers for clinical trials.
There is an expanding need for quantitative information to evaluate health and medical care procedures. Existing methods for designing and carrying out evaluation studies need to be improved to provide better techniques for answering questions on efficacy of health and medical procedures, and in providing a more adequate information base on which to set healthy policy. This paper reviews some of the problems in the design and conduct of evaluation research, and makes a plea for creation of a special discipline to support and develop the field of health and medical care evaluation.