Predicting worsening asthma control following the common cold.

The asthmatic response to the common cold is highly variable, and early characteristics that predict worsening of asthma control following a cold have not been identified. In this prospective multicentric cohort study of 413 adult subjects with asthma, the mini-Asthma Control Questionnaire (mini-ACQ) was used to quantify changes in asthma control and the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) to measure cold severity. Univariate and multivariable models were used to examine demographic, physiological, serological and cold-related characteristics for their relationship to changes in asthma control following a cold. Clinically significant worsening of asthma control was observed following a cold (mean+/-SD increase in mini-ACQ score of 0.69+/-0.93). Univariate analysis demonstrated that season, centre location, cold duration and cold severity measurements were all associated with a change in asthma control. Multivariable analysis of the covariates available within the first 2 days of cold onset revealed that the day 2 and cumulative sum of day 1 and 2 WURSS-21 scores were significant predictors of the subsequent changes in asthma control. In asthmatic subjects, cold severity within the first 2 days can be used to predict subsequent changes in asthma control. This information may help clinicians prevent deterioration in asthma control following a cold.

Data management procedures in the Asthma Clinical Research Network.

Well-designed data management processes are essential in ensuring the quality of data collected in multicenter clinical trials. This paper describes the data management processes and systems that were developed by the data coordinating center of the Asthma Clinical Research Network. A combination of manual and electronic processes has been designed to process clinical trial data from the point of collection to statistical analysis. A distributed database management system consisting of modular applications for separate data processing activities was developed to enter, track, verify, validate, and edit collected data. In addition, processes for monitoring and reporting data quality are discussed.

Implementing randomization procedures in the asthma clinical research network.

Randomization is a required component for the success of most controlled clinical trials. To ensure that the benefits of randomization are realized, well defined and carefully planned procedures must be put in place prior to the start of a trial. This paper presents a detailed account of the registration and randomization procedures implemented for the first four clinical trials of the Asthma Clinical Research Network.

Genetic analysis in the Asthma Clinical Research Network.

Because there is reason to believe that genetic variants could account for different treatment responses in subjects with asthma, it is important to collect blood for genetic-analysis purposes when conducting clinical trials in asthma. This article describes issues related to maintaining subject confidentiality, tracking and shipping blood samples, quality control procedures at the laboratory performing the genotyping, and necessary data verification checks when implementing the genetic-analysis database for the Asthma Clinical Research Network.

The role of sex hormone replacement therapy on self-perceived competence in adolescents with delayed puberty.

The objective of the present study was to determine the role of sex steroids in the development of self-perceived competence during adolescence. The Harter Self-Perception Scale was administered to 56 adolescents with delayed puberty who were receiving depo-testosterone (males) or conjugated estrogens (females) administered in 3-month blocks alternating with placebo. Treatment was given at three dose levels approximating early, middle, and late pubertal replacement levels. Hormone treatments had a significant positive effect for both males and females in one subscale domain--perceived job competence. Significant positive hormone effects were also obtained for perceptions of romantic appeal and close friendship in females and perception of athletic abilities in males. It can be inferred from the results of this study that the hormonal changes associated with sexual maturation have targeted influences on specific domains of self-perceived competence and that there are clear gender differences.

Self-assessment of physical sexual maturation in boys and girls with delayed puberty.

We studied 49 boys and girls with delayed physical sexual maturation during treatment with sex steroids. We found significant agreements, but also some disagreements between physicians' and subjects' Tanner sexual maturity ratings. We found neither effects of treatment with sex steroids nor gender differences, comparing ratings between physicians and patients.

Effects of estrogen or testosterone on self-reported sexual responses and behaviors in hypogonadal adolescents.

The purpose of this study was to investigate the effects of administration of sex steroids on self-reported sexual responses and behaviors in hypogonadal adolescents. We used a randomized, double blind, placebo-controlled, cross-over, clinical trial as the experimental design. The subjects were 39 boys and 16 girls with delayed puberty. We treated girls with oral conjugated estrogen and boys with testosterone enanthate in 3 dose levels intended to simulate early, middle, and late pubertal levels. We administered a modification of the Udry sexual behavior questionnaire after each 3-month placebo and treatment period to detect the effect of sex steroids on self-reported sexual behaviors and responses. We employed a strict intent to treat statistical analytical model. The data showed significant effects of the administration of testosterone to boys causing increases in nocturnal emission and touching behaviors at the mid- and high doses. No other treatment effects on sexual behaviors or responses were seen in boys. For girls, there was a significant increase in necking caused by the administration of estrogen only at the late pubertal dose. No other treatment effects on sexual behaviors or responses were seen in girls. We noted some gender differences for thinking about sex, sexual "turn-on," and the nature of sexual behavior. The administration of physiological doses of sex steroids to boys or girls with delayed puberty have few effects on sexual behaviors and responses.

Estrogen or testosterone increases self-reported aggressive behaviors in hypogonadal adolescents.

A randomized, double-blinded, placebo-controlled cross-over clinical trial was used to determine the role of sex steroids on the development of aggressive behaviors in 35 boys and 14 girls. Depo-testosterone (to boys) or conjugated estrogens (to girls) was administered in 3-month blocks alternating with placebo at three dose levels approximating early, middle and late pubertal amounts. The Olweus Multifaceted Aggression Inventory was administered after each placebo and treatment period to ascertain the effect of sex steroids on self-reported aggressive behaviors. We employed a strict intent-to-treat analytical model. The data demonstrated significant hormone effects on physical aggressive behaviors and aggressive impulses, but not in verbal aggressive behaviors nor aggressive inhibitions in both boys and girls. These results are the first to causally relate the administration of physiological doses of sex steroids to changes in aggressive behaviors in adolescents.

Quality control of peak flow meters for multicenter clinical trials. The Asthma Clinical Research Network (ACRN).

Although peak expiratory flow (PEF) measurements are recommended for monitoring and assessing treatment of asthmatic patients, and widely employed to assess outcome in clinical trials and epidemiologic studies, information about performance of peak flow meters (PFM) under field conditions is lacking. We describe a simple testing system consisting of a testing chamber, a spirometer, and a calibration syringe to evaluate the relative accuracy or median relative bias (MRB), precision, or inter-quartile range (IQR) of the mini-Wright PFM. The relative accuracy ranged from -4.4 to 13.2% (mean, 4.1%) and the precision from 0.06 to 11.5% (mean, 1.2%). Durability of this PFM was assessed during a 26-wk clinical trial in 255 asthmatic subjects at five centers. Seventy-one PFM (19.9%) were identified as having failed to meet acceptance criteria, predominantly because of loss of relative accuracy, by the clinics at follow-up visits (n = 36), and by the Data Coordinating Center on retrospective review of quality control measurements submitted by the clinics (n = 35). This study indicates that a simple device can be used to evaluate the relative accuracy and precision of a given PFM and to ensure the quality of PEF measurements during a clinical trial. To the extent that one can extrapolate these data to other devices, our findings indicate that the failure rate of PFM over time can be high, indicating that quality control of a PFM over time is absolutely essential in clinical trials as well as in routine clinical care.

Radiation therapy for squamous cell carcinoma of the tonsil.

OBJECTIVE: To characterize the patient population referred for radiation therapy for tonsillar cancer and to assess the effectiveness of use of only radiation therapy in this population. DESIGN: We retrospectively reviewed the medical records of 21 patients referred to the Mayo Clinic in Rochester, Minnesota, from 1970 through 1988 for radiation therapy for squamous cell carcinoma of the tonsillar region. MATERIAL AND METHODS: The median age of the 21 study patients was 65 years (range, 45 to 92), and the male:female ratio was 12:9. In all patients, follow-up continued until death or for 2.25 to 16.25 years. Of the 21 patients, 17 had tumors that were either surgically unresectable or medically inoperable, and 20 had clinical stage III or IV disease. The median total dose of irradiation was 55 Gy. RESULTS: Local control of the tonsillar cancer was as follows: T2, four of five patients; T3, seven of seven; and T4, five of nine. Thus, the local control rate was 76%. No associations were discovered among local control, total dose of radiation therapy, dose per fraction, overall duration of treatment, age, sex, or reason for referral for radiation therapy. Control of metastatic cervical adenopathy was as follows: clinical stage N1, seven of seven patients; N2, six of seven; and N3, one of one. (Six study patients had no nodal involvement.) The estimated 5-year cause-specific survival and overall survival rates were 77% and 31%, respectively. CONCLUSION: This study substantiates the effectiveness of radiation therapy in patients with squamous cell carcinoma of the tonsil.

Tonsil cancer. Patterns of failure after surgery alone and surgery combined with postoperative radiation therapy.

BACKGROUND: The authors determined the patterns of treatment failure in patients treated with surgery alone or surgery combined with postoperative radiation therapy for squamous cell carcinoma of the tonsil. METHODS: Seventy-two patients underwent surgery alone (56) or surgery and postoperative adjuvant radiation therapy (16). All patients were followed up until death (40 patients) or for a minimum of 3.5 years. For patients treated with surgery alone, clinic notes, operative notes, and pathology reports and slides were reviewed to identify clinical or pathologic predictors of recurrence above the clavicles, cause-specific survival, and overall survival. For patients undergoing postoperative adjuvant radiation therapy, demographic, treatment, and pathologic variables were analyzed to identify factors associated with control of disease above the clavicles, disease-free survival, and overall survival. RESULTS: The main pattern of treatment failure was above the clavicles. It occurred in 39% of patients treated with surgery alone and was significantly related (P = 0.002) to the overall clinical TNM stage. Disease recurrence above the clavicles occurred in 31% of patients undergoing surgery and postoperative adjuvant radiation therapy, despite their more advanced neck disease. Five-year overall survival for patients with clinical Stage III and IV disease who were treated with surgery and post-operative adjuvant radiation therapy was 100% and 78%, respectively. Five-year overall survival for patients treated with surgery alone who had clinical Stage III, IVA, or IVB disease was 56%, 43%, and 50%, respectively. CONCLUSION: We recommend postoperative adjuvant radiation therapy for patients with clinical Stage III or IV squamous cell carcinoma of the tonsil who have undergone complete surgical resection because this appears to improve control of disease above the clavicles and overall survival.

A randomized clinical trial of two different durations of oral cryotherapy for prevention of 5-fluorouracil-related stomatitis.

BACKGROUND: The authors previously reported that 30 minutes of oral cryotherapy inhibits 5-fluorouracil (5-FU)-induced stomatitis. The current trial was designed to determine whether a longer duration of cryotherapy would provide additional protection. METHODS: This trial involved patients who were receiving their first course of a 5-FU plus leucovorin chemotherapy regimen, for which stomatitis is a major dose-limiting toxicity. These patients were randomized to receive either 30 or 60 minutes of oral cryotherapy given at around the same time as the 5-FU therapy. RESULTS: A total of 178 evaluable patients were studied. Both cryotherapy groups had similar degrees of mucositis. CONCLUSION: The authors continue to recommend the use of 30 minutes of oral cryotherapy for patients receiving bolus intensive courses of 5-FU-based chemotherapy.

Base of tongue carcinoma: patterns of failure and predictors of recurrence after surgery alone.

Between January 1971 and December 1986, 55 patients with squamous cell carcinoma of the tongue base underwent complete surgical resection with curative intent. No preoperative or postoperative adjuvant therapy was administered. The study group consisted of 41 men and 14 women (median age 61 years). All patients were followed until death (39 patients) or for a median of 9.4 years. Local control at 5 years was 74%. No predictors of local recurrence were discovered. Control in the dissected neck at 5 years was 68%. Control of cancer above the clavicles at 5 years was 48%. Distant metastases developed in 14% of the patients by 5 years. Cause-specific survival at 5 years was 65%. A Cox multivariate regression analysis revealed that pathologic N stage was the only significant independent predictor of recurrence in the dissected neck, recurrence above the clavicles, and cause-specific survival. The 5-year overall survival was 55%. Surgical mortality was 4%.

Early-stage squamous cell carcinoma of the glottic larynx managed with radiation therapy.

Between January 1975 and December 1985, 45 patients with carcinoma in situ or invasive squamous cell carcinoma of the glottic larynx received radiation therapy at the Mayo Clinic. Local control in the entire group of 45 patients was 84% (in 6 of 6 with carcinoma in situ and in 32 of 39 with invasive cancers). Three of seven patients (43%) with local recurrences underwent successful larynx-preserving surgical procedures; thus, the rate of laryngeal preservation was 91%. In our study of several treatment factors, including the duration of treatment, type of treatment (continuous course versus split course), photon energy (60Co versus 4-MV photons versus 6-MV photons), total dose, and dose per fraction, we found that only total dose of 6,300 cGy or more was associated with significantly improved local control (in 35 of 38 patients [92%]). Two patients (4%) died of uncontrolled delayed nodal metastases, one of which was preceded by a local recurrence. Severe laryngeal edema developed in two patients, associated with recurrent glottic carcinoma in one of them. No larynx was lost because of complications. In our current treatment recommendations, patients receive a total dose of 6,300 cGy in 28 fractions of 225 cGy each, administered in a continuous course with use of 6-MV photons.