A dose ranging study of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) in healthy infants.

BACKGROUND: Two new formulations of an investigational 15-valent pneumococcal conjugate vaccine (PCV15-A and PCV15-B) were developed using 2 different protein-polysaccharide conjugation processes and evaluated in separate phase I/II studies (NCT02037984 [V114-004] and NCT02531373 [V114-005]) to assess optimal concentrations of pneumococcal polysaccharide (PnPs) and Aluminum Phosphate Adjuvant. METHODS: Various lots of PCV15-A and PCV15-B containing different concentrations of PnPs and/or adjuvant were compared to PCV13 in young adults and infants. Adults received single dose and infants received 4 doses at 2, 4, 6, and 12-15 months of age. Adverse events (AEs) were collected after each dose. Serotype-specific immunoglobulin G (IgG) concentrations and opsonophagocytic activity (OPA) were measured prior and 30 days postvaccination in adults, at 1 month postdose 3 (PD3), pre-dose4, and postdose 4 (PD4) in infants. RESULTS: Safety profiles were comparable across vaccination groups. At PD3, serotype-specific IgG GMCs were generally lower for either PCV15 formulation than PCV13 for most shared serotypes. PCV15 consistently elicited higher antibody responses to the 2 serotypes unique to the vaccine (22F and 33F) and serotype 3 for which PCV13 was shown to be ineffective. Except for serotypes 6A and 6B, no dose-response effect was observed with increasing concentrations of PnPs and/or adjuvant. CONCLUSION: PCV15 is safe and induces IgG and OPA responses to all 15 serotypes in the vaccine. No significant differences in antibody responses were observed with increases in PnPs and/or Aluminum Phosphate Adjuvant.

Strategies for comparing treatments on a binary response with multi-centre data.

This paper surveys methods for comparing treatments on a binary response when observations occur for several strata. A common application is multi-centre clinical trials, in which the strata refer to a sample of centres or sites of some type. Questions of interest include how one should summarize the difference between the treatments, how one should make inferential comparisons, how one should investigate whether treatment-by-centre interaction exists, how one should describe effects when interaction exists, whether one should treat centres and centre-specific treatment effects as fixed or random, and whether centres that have either 0 successes or 0 failures should contribute to the analysis. This article discusses these matters in the context of various strategies for analysing such data, in particular focusing on special problems presented by sparse data.

Dynamic versus static grip strength: how grip strength changes when the wrist is moved, and why dynamic grip strength may be a more functional measurement.

The synergistic relationship between wrist/forearm range of motion (ROM) and grip strength (GS) is arguably one of the most important aspects of hand function. Clinically, GS is measured with the wrist in a standardized static position, and the results of such tests have been deemed valid and reliable. The question remains, however, whether this static GS (SGS) measurement is an accurate indication of how an individual functionally grips objects--that is, most functional tasks require the fingers to grasp an object forcibly while moving the proximal joints such as the wrist and forearm. Therefore, further analysis of an individual's dynamic GS (DGS) during wrist/forearm movements may improve the clinician's understanding of hand function and provide more pertinent guidelines for assessing functional gripping, e.g., for vocational and avocational tasks and in designing workstations. The purpose of this study is twofold: to describe and assess a DGS testing device that utilizes optically encoded gyroscopes and a strain-gauge dynamometer to simultaneously measure GS and wrist/forearm position over real time; and to assess and compare grip force production differences in SGS and DGS in uninjured wrists, using this novel device. Twenty-nine uninjured wrists of men (n = 15) and women (n = 14)--age range, 21 to 43 years--were tested with the DGS device. Subjects were excluded if they had any previous wrist/forearm fracture, pain, or limitation of motion. The DGS device was designed and fabricated with two optically encoded gyroengines, a vertical gyroscope with two axes for measuring flexion/extension and radial/ulnar deviation, and a directional gyroscope with one axis for measuring supination/pronation, mounted on a strain-gauge dynamometer. The signals from the gyroscopes and dynamometer were processed by means of a data aquisition board and analog-to-digital circuitry and collected on a 486-MHz computer. The methods included repeated testing of each gyroscope axis to known angular measurements, and randomly assigned maximal gripping trials from the 29 subjects. The standard deviation of gyroengines is 1 degree to 2 degrees for each ROM axis. Maximal DGS is significantly less (mean 14%) than SGS, and SGS is 29% less than DGS at the same three-dimensional ROM positions. Gyroengines are feasible three-dimensional tracking devices that can be used to monitor wrist/forearm ROM in conjunction with GS.

Caudal slope of the tibia and its relationship to noncontact injuries to the ACL.

To determine the role that an increased caudal slope of the tibia might have on the incidence of anterior cruciate ligament (ACL) injury, tibial slope was measured in 49 patients (50 knees), with noncontact ACL injury mechanisms (group 1) and an age-matched group of 39 patients (50 knees) with a diagnosis of patellofemoral pain syndrome (group 2). No significant difference was noted in mean posterior slope between the two groups (group 1: 9.7+/-1.8 degrees and group II: 9.9+/-2.1 degrees) or after controlling for bilateral patients in two separate trials. These results indicate that increased caudal tibial slope does not appear to be a risk factor in the creation of noncontact injuries to the ACL.

Continuous passive motion after repair of the rotator cuff. A prospective outcome study.

Despite the apparent success of continuous passive motion after soft-tissue procedures or joint replacements, its effect after repair of the rotator cuff is still unknown. The purpose of this prospective, randomized outcome study was to compare the results of continuous passive motion with those of manual passive range-of-motion exercises after repair of the rotator cuff. Thirty-one patients (thirty-two rotator cuffs) were randomly assigned to one of two types of postoperative management: continuous passive motion (seventeen patients) or manual passive range-of-motion exercises (fifteen patients). There were seventeen women and fourteen men, and the mean age was sixty-three years (range, thirty to eighty years). The patients were followed for a mean of twenty-two months (range, six to forty-five months). Five tears of the rotator cuff were small, eighteen were medium, and nine were large. All of the operations were performed by one surgeon. The patients who were managed with continuous passive motion used the device for the first four weeks postoperatively. The patients who were managed with manual passive range-of-motion exercises were assisted by a trained relative, friend, or home-care nurse. After the four-week period, the two groups were managed similarly for two to five months. According to the Shoulder Pain and Disability Index, a valid and reliable self-administered questionnaire, the treatment was extremely successful in both groups. The overall score was excellent for twenty-seven shoulders (84 per cent), good for two (6 per cent), fair for two (7 per cent), and poor for one (3 per cent). With the numbers available, we could detect no significant differences (p > 0.05) between the two groups with respect to the score according to the Index, pain (according to a visual-analog scale), range of motion, or isometric strength. Manual passive range-of-motion exercises were more cost-effective than continuous passive motion. The limited number of physical-therapy visits associated with the manual passive range-of-motion exercises in the present study appeared to be more cost-effective than a traditional physical-therapy schedule of three visits per week. Postoperative therapy with continuous passive motion or manual passive range-of-motion exercises appears to yield favorable results after repair of a small, medium, or large tear of the rotator cuff.

Owner satisfaction with partial mandibulectomy or maxillectomy for treatment of oral tumors in 27 dogs.

Twenty-seven dogs with oral tumors were treated with either rostral mandibulectomy, partial mandibulectomy, or partial maxillectomy. Owner satisfaction with the respective surgical procedure was assessed by telephone survey; 85% of owners were satisfied with the decision to treat their dogs. The percentage of satisfied owners was directly proportional to the increase in pet life span. Although difficulty in eating was noted for 12 (44%) of 27 dogs, pain was perceived to be reduced by the surgery for most animals. All owners found the cosmetic appearances of their dogs acceptable after facial hair regrew. The quality of the pets' lives was perceived by the owners to be most improved after rostral mandibulectomy and least improved after partial maxillectomy.

Population-averaged and cluster-specific models for clustered ordinal response data.

We compare population-averaged and cluster-specific models for clustered ordinal data. We consider generalized estimating equations and constrained equations maximum likelihood estimation of population-averaged cumulative logit regression models, and mixed effects estimation of cluster-specific cumulative logit regression models. A previously reported relationship between population-averaged and cluster-specific parameters for the binary logistic link appears to hold for analogous parameters under the cumulative logit link. We address these issues in the context of data from two cross-over clinical trials.

The impact of 2D versus 3D quantitation of tumor bulk determination on current methods of assessing response to treatment.

PURPOSE: Measurements from sequential axial "2D" data in cancer patients are commonly used to assess treatment response or disease progression. This study compares the volume of tumor bulk calculated with 3D reconstructions with that calculated by conventional methods to determine if it might change patient classification. METHOD: All medical, gynecologic, and pediatric oncology patients under treatment who were evaluated with serial CT scans between January 1, 1992, and July 31, 1994, for whom the digital data were available were included in this study. For each tumor site, the maximum diameter and its perpendicular were measured and multiplied together to yield an area. The sum of areas of the measured lesions was used as an approximation of overall 2D tumor volume. In addition, the 2D area of each site was multiplied by its height, yielding a 2D volume. Last, the digital data were loaded into a 3D computer system and total 3D tumor volumes determined. All medical and gynecologic oncology patients were treated based upon the 2D area of tumor. The pediatric oncology patients were treated based upon the 2D volume of tumor measured as per standard practice. The members of each treating oncologic service assessed their patients as to how the other two methods would have changed their classification of the patients' response category. RESULTS: Four hundred thirty-three CT scans were performed in 139 patients, which included 204 baseline and 294 follow-up CT examinations. Seventy patients had new tumor foci and would have been classified as failure by all three methods of tumor bulk measurement. The 3D volume versus the 2D area method of tumor bulk assessment would have changed response categories in 52 of the 294 follow-up CT examinations (p < 0.0001). Thirty-five patients were recategorized from either "no response" to "failure" (21 patients) or "no response" to "response" (14 patients) categories. If only those follow-up studies without new metastatic foci are considered, the 3D volume versus the 2D area methods of tumor assessment would have changed the treatment response category in 23.2%. The use of the 2D volume method of calculating tumor volume of bulk tended to overestimate the overall tumor size by an average of 244 cm3 (p = 0.001). CONCLUSION: The 3D method of tumor volume measurement differs significantly from conventional 2D methods of tumor volume determination. Large prospective studies analyzing the usefulness of 3D tumor volume measurements and assessing possible changes in patient response categories would be required for full utilization of this more accurate method of following disease bulk.

The quality of 3D reconstructions from 1.0 and 1.5 pitch helical and conventional CT.

PURPOSE: CT data are commonly used to create 3D images. For this purpose, thin and overlapped slices are desirable. Helical (spiral) CT offers the ability to adjust the slice reconstruction interval from 0 to 100%. However, its use in 1.0 and 1.5 pitch helical CT and 3D imaging, especially with respect to surface detail, is relatively untested. METHODS: Ten objects selected for their varying size, shape, and density were scanned (fourth generation Picker PQ2000) by contiguous 2,4 and 8 mm conventional and helical sequences. The latter were obtained with a pitch of both 1.0 and 1.5 and were reconstructed into a 3D image with 0-75% overlapping of the reconstructed slices. Each of the 24 different sequences per scanned object was reconstructed into identical sets (projections) of 3D images displayed on color film. The 24 3D image sets for each object were submitted to six blinded radiologists who separately ranked them from best to worst. RESULTS: 3D reconstructions obtained from CT scans with a thinner slice thickness, half-field (15 cm FOV), and helical technique were rated as statistically superior. The 1.0 and 1.5 helical sequences obtained with a 4 or 8 mm slice thickness scored statistically better than 3D reconstructions from equivalent conventional scans. Overlapping of the reconstructed helical slices by 25-75% generally improved the quality of the 3D reconstruction. CONCLUSION: Helical CT with either a 1.0 or a 1.5 pitch offers the ability to obtain higher quality 3D reconstructions than from comparable conventional CT scans.

Take-home informed consent for intravenous contrast media: do patients learn more?

RATIONALE AND OBJECTIVES: In 1978, Morrow et al published the results of a simple technique for raising radiation oncology patients' levels of awareness about medical options. They reported that providing written information at least 24 hours in advance was an effective tool for increasing the baseline knowledge in this patient group. However, Morrow's cohort consisted exclusively of cancer patients receiving radiation therapy. The authors of this article are concerned with whether the encouraging results reported by Morrow are reproducible when applied to patients awaiting invasive radiologic procedures. METHODS: One hundred sixty consecutive outpatients awaiting contrast were block randomized into one of eight groups based on age, sex, and previous contrast exposure. For each group, half were given their consent form at least 24 hours prior, and the other half at the time of their procedure. All patients were tested at the time of their procedure to evaluate knowledge retention. RESULTS: Comparison between the two study groups showed no overall statistically significant differences either in knowledge (experimental group 4.7 +/- 1.32 versus 4.38 +/- 1.30 control group) or level of satisfaction. Additionally, individuals experienced with contrast failed to outperform those who had never previously been given contrast. There is no significant difference in the performance between the two sexes regardless of group. CONCLUSIONS: The providing of information 24 to 72 hours in advance of an invasive procedure does not have a beneficial effect over just providing the same information at the time of the study.

Multiple fine-needle biopsies using a coaxial technique: efficacy and a comparison of three methods.

PURPOSE: Compare the success of three coaxial fine-needle biopsy techniques in obtaining multiple cytologic specimens of high quality. METHODS: For each of three different biopsy needle and technique combinations (aspiration: 22-gauge Chiba; capillary: 22-gauge Chiba; 22-gauge Autovac aspiration biopsy gun), 30 sites (15 liver, 15 kidney) were selected for coaxial fine-needle biopsy in cadaveric liver and kidneys. For each coaxial technique, three sequential biopsies were performed through an 18-gauge coaxial needle at each of multiple sites. The quality of the resultant 270 specimens was graded by a blinded cytopathologist using a previously published grading scheme. RESULTS: Using the coaxial technique, there was no significant dropoff in the cytologic specimen quality among the first, second, and third biopsies at a specific site, regardless of the order of the techniques/needles used. This was true for organs, the overall data, and for the individual five grading criteria. There was, however, a significant difference among the biopsy techniques themselves. Though there was no difference in the quality of cytopathologic specimen obtained with the Autovac aspiration gun and the aspiration technique with a 22-gauge Chiba needle, both were statistically better than the nonaspiration, capillary technique utilizing a 22-gauge needle (p = 0.0001). CONCLUSION: The use of a coaxial technique with a fine-needle, 22-gauge biopsy offers unique advantages in obtaining a nearly unlimited amount of high-quality material for cytopathologic analysis. In this study, no dropoff was found in specimen quality with subsequent biopsies.

Fine-needle aspiration biopsy versus fine-needle capillary (nonaspiration) biopsy: in vivo comparison.

PURPOSE: To evaluate, in vivo, the efficacy of fine-needle capillary (nonaspiration) biopsy (FNCB) versus fine-needle aspiration biopsy (FNAB) when performed at the same site with a coaxial technique. MATERIALS AND METHODS: In 91 patients, biopsy was performed at 140 sites in 93 lesions mostly throughout the chest and abdomen with either FNCB or FNAB, or both (98 sites). A coaxial technique with a 22-gauge needle was used. The quality of the specimen was graded by a blinded pathologist, who also made a pathologic diagnosis. RESULTS: No statistically significant difference was noted in the graded criteria performance plus diagnostic yield between the two techniques. When performed before FNAB, FNCB yielded a better quality specimen of a particular site. However, there was no difference in the graded quality of FNAB whether performed before or after FNCB. Insufficient specimens were obtained at 30 (21.4%) of 140 sites with FNCB versus only 18 (12.8%) with FNAB. CONCLUSION: FNCB is an alternative to FNAB and provides a cellular diagnostic specimen from most lesions. When a coaxial method is used and both techniques are employed, the diagnostic accuracy of these techniques is 84%.

Informed consent forms for clinical and research imaging procedures: how much do patients understand?

OBJECTIVE: Informed consent is often obtained in diagnostic radiology, especially for invasive procedures and research studies. However, how much the average patient actually understands of the information contained in these informed consent forms is uncertain. A cross section of the clinical and research consent forms used in diagnostic radiology was evaluated with respect to their readability, that is, how easy or difficult they were to understand. MATERIALS AND METHODS: The active members of the Association of University Radiologists were solicited to provide copies of their clinical and research informed consent forms. After eliminating duplicates, we digitized the forms and used a computer program to evaluate their readability. Computer readability assessment allows the rapid study of an entire document by a variety of readability formulas (Flesch-Kincaid, Flesch, and Fog). RESULTS: We received 549 different consent forms from 156 institutions; 265 forms were intended primarily for clinical use and 284 were used primarily for research. Although the clinical consent forms were only 41% as long as those for research, a statistical comparison showed them to be harder to understand (p < 0.005). The mean readability score (years of education needed to understand) for all 265 clinical consent forms was 15 versus 12 for the research forms. The most complex clinical consent forms were those written by hospitals for any type of procedure or operation (the generic surgical or procedure consent form). On average, this type of clinical consent form required at least a college education to understand. CONCLUSION: Our results show that most consent forms used in radiology practice are too complex for the average patient to understand. The increased complexity of clinical consent forms, especially the generic surgical or procedure consent forms, as compared with research consent forms, is probably a product of the decreased attention given to the clinical consent forms, the bureaucratic and legal requirements of the clinical forms, and the lack of physician participation in preparing these forms.

CT percutaneous biopsy guns: comparison of end-cut and side-notch devices in cadaveric specimens.

OBJECTIVE: The purpose of this study was to compare the efficacies of four different types of end-cut biopsy guns with the side-notch Tru-cut biopsy gun. MATERIALS AND METHODS: A total of 25 liver, 15 kidney, 10 pancreas, and 15 breast biopsies were performed in the tissue from five autopsies with each of 12 different biopsy devices/biopsy depths. The tissue obtained was evaluated by an experienced cytopathologist who, not knowing which gun was used to obtain each specimen, used a predetermined grading scheme. RESULTS: When tissue was obtained, the end-cut biopsy guns performed equivalently to the side-notch biopsy gun in all four tissues. However, the end-cut guns had a significant number of "zero" biopsies (biopsy attempts during which no tissue was obtained). The proportion of zero biopsies with the end-cut guns ranged from up to 28% in the liver to 60% and 73% in the breast and kidney, respectively. CONCLUSION: The end-cut biopsy guns are easy to use and potentially can obtain high-quality specimens. However, the rate of zero biopsies during which no tissue is obtained is a serious deficiency. As a result, the use of the end-cut biopsy gun should be encouraged only for use with an introducer, with which multiple biopsy specimens can easily be obtained without additional needle punctures.

Percutaneous biopsy of the liver and kidney by using coaxial technique: adequacy of the specimen obtained with three different needles in vitro.

OBJECTIVE: The coaxial biopsy technique was evaluated with respect to the quality of specimens obtained from the liver and kidneys in vitro on sequential biopsies at the same site with each of three different biopsy needles. MATERIALS AND METHODS: For each of three different biopsy needles (aspiration 18-gauge Chiba, 18-gauge Sure-Cut, and 18-gauge Biopty), 30 sites (15 liver, 15 kidney) were selected for in vitro coaxial biopsy. At each site, an introducer was placed, through which three sequential biopsies were done. Blinded histopathologic analysis was used to grade the quality of specimens on a scale from 0 (no tissue) to 3 (best) for three criteria: adequacy of tissue for diagnosis, tissue fragmentation, and crush artifact. The overall score was the sum of the scores for the three individual criteria and ranged from 0 (no tissue) to 9 (best). RESULTS: Using an 18-gauge Chiba needle and coaxial technique, we found no significant reduction in specimen quality when we did multiple aspiration biopsies at the same site. However, no tissue was obtained (zero biopsy) from a large number of aspiration biopsies done with the Chiba needle, ranging from 24 of 30 for the first biopsy to 17 of 30 for the third biopsy. Specimen quality was reduced somewhat between the first and third biopsies when the 18-gauge Sure-Cut and Biopty needles were used. With the Sure-Cut needle, this reduction in quality was significant (p = .009) and was primarily related to increased tissue fragmentation and crushing. The reduction in quality with multiple biopsy attempts was less severe with the Biopty needle/gun. Although the mean score decreased from 6.6 for the first biopsy to 5.5 for the third biopsy, this reduction was not significant (p = .06). In addition, the Biopty gun, unlike the other two needles, had few zero biopsies. CONCLUSION: The use of a coaxial technique with an 18-gauge Biopty needle enables collection of a large amount of high-quality tissue for histopathologic analysis with a minimum number of failed biopsies as compared with the 18-gauge Chiba needle and the 18-gauge Sure-Cut needle.

The effect of informed consent on the level of anxiety in patients given i.v. contrast material.

OBJECTIVE: A common reason given for not obtaining informed consent before the use of IV contrast material is that the anxiety created by informing patients of potential reactions will increase the possibility of their occurring. However, the idea that this is possible is debatable, and no study of this subject has used a standardized anxiety index. Accordingly, using the State-Trait Anxiety Inventory, we assessed the anxiety level among patients about to have an IV contrast procedure and measured the effect of informing them of the risks associated with the use of contrast material. SUBJECTS AND METHODS: Approximately 2050 adult outpatients at three separate medical centers were solicited for participation in this study. Each of the 1251 patients who volunteered to participate was placed into one of six groups. The majority were patients who were awaiting the injection of either ionic or nonionic contrast material and who were or were not informed of the risks associated with the use of IV contrast material. The last two groups were generally healthy outpatients reporting for routine X-rays who were not awaiting IV contrast administration but who were informed of the risks associated with the use of ionic and nonionic contrast material. Each patient informed of the risks was asked to read a standardized consent form, and all patients completed a standardized anxiety index. RESULTS: Patients who were informed of the risks associated with IV contrast material did not have measurably increased anxiety, and they did not have an increased prevalence of adverse reactions. Indeed, the only patients who had statistically significant increased anxiety compared with the other groups were among those awaiting the injection of ionic contrast material who were not informed of the risks (p = .04). The majority (51-78%) of patients in all six groups had measurable elevated anxiety scores. CONCLUSION: We conclude that it is not justified to fail to obtain informed consent in order to avoid anxiety-induced adverse reactions to IV contrast material. The majority of patients awaiting injection of IV contrast material have measurable increased anxiety levels regardless of whether they are informed of its risks.