Reporting the study populations of clinical trials. Clear transmission or static on the line?

In contrast to attempts that have been made to measure the clarity of reporting of the methods of clinical trials in journal articles, we report here an attempt to measure the accuracy of methods reporting. We focus in this article on eligibility criteria as a test case for the reporting of clinical trial methods. We examined the reporting of eligibility criteria in the protocol, methods paper (if applicable), journal article, and Clinical Alert for articles appearing in print between January 1988 and September 1994 for which a Clinical Alert had been issued. Eligibility criteria were further classified into five categories in order to examine the content of information loss, if any. On average, 82% of protocol eligibility criteria were reported in methods papers. Journal articles and Clinical Alerts fared somewhat worse: 63% of criteria were reported in journal articles, 19% in Clinical Alerts. In all three categories of medical communication, the reporting of criteria that defined the study disease tended to be complete; reporting of criteria relating to trial precision, patient safety, legal and ethical concerns, and administrative considerations, was not complete. We found that criteria for clinical trial eligibility are frequently under-reported in medical communications. Moreover, some of the criteria omitted are of considerable clinical importance. We suggest that in the design phase of clinical trials, proposed eligibility criteria be scrutinized closely. Those criteria that survive this scrutiny and that have clinical import must be reported upon fully and accurately when communicating trial results.

Comparing participants and nonparticipants in a smoking cessation trial: selection factors associated with general practitioner recruitment activity.

We studied the relationship between smokers' sociodemographic characteristics, their smoking habit, health status, and the probability of their having been approached for recruitment in the smoking cessation trial performed in Turin, Italy, with the aim of gathering information on the role of selection criteria adopted by general practitioners (GPs) in offering anti-smoking counseling. The 965 smokers who were offered participation in the trial were matched to a sample of eligible smokers (n = 277), selected from the rosters of the 42 GPs collaborating in the trial, who had not been invited to participate. The probability of being offered enrollment, estimated through a multiple conditional logistic regression model, assuming the GP as the matching variable, was significantly increased for intermediate (10-19 cigarettes per day: odds ratio [OR] = 4.13; 95% confidence interval [CI]: 2.63-6.47) and heavy (20 cigarettes per day or more: OR = 10.12; 95% CI: 6.51-15.75) smokers, for smokers diagnosed with chronic cardiovascular (OR = 2.06; 95% CI: 1.19-3.58), or respiratory (OR = 2.50; 95% CI: 1.40-4.48) diseases, and for smokers mentioning an intermediate number (2-4) of past quit attempts (OR = 3.70; 95% CI: 2.18-6.28). General Practitioners focused their recruitment activity on higer-risk smokers or smokers who had tried to quit, to offer more clues for intervention. Assessing the potential public health benefit of preventive interventions requires a more systematic evaluation of the generalizability of the reported findings.

A randomized clinical trial of negative pressure ventilation in severe chronic obstructive pulmonary disease: design and methods.

This report documents the design and methods of a randomized clinical trial designed to test the effectiveness of home negative pressure ventilation in patients with severe chronic obstructive pulmonary disease. Active negative pressure ventilation was compared with a sham version of the treatment after a pre-trial assessment had indicated the feasibility of the latter. Over 1200 patients in the metropolitan Montreal area were screened. Of these, 348 patients were recruited to enter a 4-week stabilization period, and 184 were subsequently randomized to receive either active or sham negative pressure ventilation. A 5-day in-hospital period was used to train patients in ventilator use and obtain baseline measures of exercise capacity, lung function, respiratory symptoms, and quality of life. Home ventilation treatment took place during a following 12-week period. Respirator use was recorded both from patient logs and from concealed meters installed in the units. Patients received four home visits by physiotherapists during the 12-week period and returned for follow-up to the hospital 4 and 12 weeks post-discharge for reassessment.

Serial light and electron microscopic changes in renal glomeruli in mice fed griseofulvin.

The renal glomerular mesangium in male, Swiss Webster mice, fed a diet containing 2.5 percent griseofulvin (GF), showed hypercellularity and mesangial thickening within three weeks. These changes gradually increased, peaking in prominence at 11 to 16 weeks and persisted up to 22 weeks. The tubular epithelium showed minimal light microscopic changes. There was focal hyperplasia of parietal cells of the Bowman's capsule. Ultrastructurally, the changes in the mesangial region of the glomeruli included increase in mesangial cells and mesangial matrix. The renal tubular epithelial cells showed dilatation of mitochondria and smooth endoplasmic reticulum. These changes, in addition to diverse cellular alterations in other organs previously reported, constitute the morphologic features of GF-induced renal disease.

Rhodamine B fluorescence as a stain for amniotic fluid squames in maternal pulmonary embolism and fetal lungs.

Rhodamine B fluorescence is presented as a simple, rapid, highly sensitive, permanent method for the histologic detection of squames in maternal amniotic fluid emboli and fetal lungs in cases of intrauterine asphyxia. The method may be used on alcohol fixed smears or formalin fixed paraffin sections. The application of this procedure allows for identification of sparsely distributed fetal squames which otherwise may be overlooked by less sensitive tinctorial methods which may also be more tedious in technical preparation and screening.

Ultrastructural changes of intrahepatic bile ductules in griseofulvin fed mice.

Intrahepatic bile ductules in male Swiss Webster mice, fed a diet containing 2.5 percent griseofulvin (GF), showed marked hypertrophy and hyperplasia within two weeks. Thereafter, this reaction gradually increased in prominence until nine weeks. Cytoplasmic acid phosphatase and succinic dehydrogenase deposits were more prominent and abundant after 12 to 14 weeks. Ultrastructural changes in ductular epithelial cells included enlargement of nuclei and nucleoli and increased abundance of cytoplasmic rough surfaced endoplasmic reticulum (RER), ribosomes and mitochondria until nine to 12 weeks. At this interval, duct lumina appeared widely dilated with small clumps of electron dense material at the periphery adjoining apical cell membranes with severely flattened or absent microvilli. Electron dense needle-like crystals resembling protoporphyrin were clustered centrally in the lumina. After twelve weeks occasional mitochondria were markedly swollen and contained vacuolated areas. Numerous multivesicular bodies were noted. Mallory bodies were seen in a few duct cells. The spectrum of duct cell changes just noted gives further evidence of extensive liver injury after GF feeding. These changes, in addition to diverse hepatocyte alterations previously reported, constitute morphologic features of GF induced murine porphyria, also common to human porphyria and human alcoholic liver disease.

Focal nodular hyperplasia of the liver: ultrastructural observations.

Ultrastructural studies of the liver from a non-alcoholic 21 year old male with focal nodular hyperplasia (FNH) showed hepatocyte cytoplasmic alterations including swollen and bizarre mitochondria, rough endoplasmic reticulum (RER) in short parallel stacks or whorl-like arrangements, and Mallory bodies (MB). Proliferated bile duct cells contained occasional MB-like inclusions. Small hepatic blood vessels were dilated and some showed interruption and partial loss of their endothelial cell cytoplasm and thickened basement membranes. Liver tissue outside of the lesion appeared unaltered.

Hepatocyte mitochondrial alterations in griseofulvin fed mice.

Ultrastructural changes in mitochondria from hepatocytes of male Swiss Webster mice were observed during the course of porphyria induced by ingestion of a powdered diet containing 2.5 percent griseofulvin (GF). A variety of sporadic mitochondrial alterations were noted between three days and 22 weeks. Mitochondria appeared intact in hepatocytes from control mice fed powdered diet alone. The abundance and prominence of altered mitochondria increased after seven weeks and was particularly apparent after 15 weeks, concurrent with pronounced hepatomegaly and Mallory body (MB) formation. One or more changes observed in some mitochondria of several hepatocytes included: swelling, associated myelin bodies, increased matrix density, disoriented cristae, intracristal swelling, bizarre shapes, paracrystalline inclusions and elongated or spherulated giant forms. Many mitochondria showed intimate association with rough surface endoplasmic reticulum (RER) adjacent to smooth surface endoplasmic reticulum (SER). GF-induced mitochondrial defects appear to represent nonspecific morphologic alterations similar to many reported in human hepatocytes in alcoholic liver disease, porphyria and various other toxic and metabolic liver diseases. They may reflect another common site of metabolic insult between two such diverse processes as GF-induced mouse porphyria and human alcoholic liver disease.

Light and electron microscopy of hepatocellular changes in griseofulvin fed mice. Particular reference to Mallory bodies.

Male Swiss Webster mice were fed a diet containing 2.5 percent griseofulvin (GF). Serially progressive light and electron microscopic hepatic altertions were present from one day on and grossly visible hepatomegaly from two weeks until termination at 22 weeks. GF induced liver changes included hepatocyte nuclear and cytoplasmic hypertrophy, increased incidence of necrosis and mitosis, Kupffer cell activation, bile duct proliferation and portal fibrosis. Protoporphyrin crystals were present in hepatocyte cytoplasm as early as one day after GF feeding. Hepatocellular hyalin was initially noted at seven weeks. Thereafter, the hyalin increased in prominence and frequency of occurrence. Ultrastructurally, three types of hyalin have been presently demonstrated to correspond to Mallory bodies (MB) reported in human liver disease. Forms intermediate in appearance between various MB types suggested transition from one to another. Areas of organelle free cytosol with abundant, loosely scattered filamentous elements as well as vesicular, smooth surfaced endoplasmic reticulum and ribosomes appeared preceding and closely associated with MB formation. Similarities of hepatocellular MB observed in GF fed mice and reported earlier in human alcoholic liver disease suggest a common pathway in its formation as a response to divergent noxious insults.

RNA virus associated antigen in human placenta.

Using indirect immunofluorescence microscopy, it was demonstrated that human cytotrophoblast of six to ten weeks gestation contains mouse mammary tumor virus associated antigen. This antigen appeared predominantly in the periphery of the cells.

Determinants of patients' treatment preferences in a clinical trial.

Several researchers have suggested that patients' preferences for a particular form of treatment should be taken into account in clinical trials. Preferences may influence the outcome of treatment, especially in trials when patients cannot be blinded to the type of treatment received and the outcome is based on patients' evaluations of therapy. Participants in this study were 136 edentulous patients who took part in a randomised controlled clinical trial comparing two types of treatments for edentulism: conventional dentures and implant-supported prostheses. Prior to receiving treatment, subjects were required to complete a questionnaire regarding their satisfaction with their present prostheses. In addition, they were asked to indicate which treatment they would prefer if given a choice. The objective of this study was to determine whether there are important differences among study participants between patients who have a treatment preference and those who do not. The effects of satisfaction with pre-treatment prostheses, age, gender and level of education on preferences were examined. Level of satisfaction with the original dentures and level of education were significant predictors of preference. Compared to subjects who rated their satisfaction with their current condition as 'low', the odds ratios associated with having a preference for implant treatment were 0.31 (95% CI: 0.09 to 0.96) for subjects who rated their prostheses in the 'medium' range and 0.11 (95% CI: 0.03 to 0.41) for those who rated in the 'high' range. In addition, subjects with high levels of education were significantly less likely to have a preference for either conventional or implant treatments (OR = 0.18, 95% CI: 0.02 to 0.77 and OR = 0.20, 95% CI: 0.05 to 0.76, respectively) compared to those with low education. Neither age nor gender was a significant predictor of preference. We suggest that study designs which incorporate patients' preferences must take into account possible differences between preference groups that might confound the relationship between preference and the outcome of interest.

On parallel processes in therapy and teaching.

Using the format of a continuous case conference, the authors demonstrate that the therapist-presenter develops unconscious identifications with the patient which are especially intense when difficulties (resistances) arise which he cannot resolve. The presenter then enacts these identifications in the seminar giving rise to responses from the seminar members which repeat the difficulties of the therapy. These parallel processes can be made explicit by eliciting the empathic responses of the seminar participants. By interpreting these parallelisms the authors have evolved a teaching methodology which, like therapy itself, provides an emotionally based learning experience for the participants.