Fall frequency and risk assessment in early Parkinson's disease.

BACKGROUND: We sought to define the frequency of falls in early PD and assess potential risk factors for falls in this population. METHODS: We analyzed the data from two randomized, placebo controlled trials (NET-PD FS1 and FS-TOO) of 413 individuals with early PD over 18 months of follow-up in FS1 and 12 months in FS-TOO. Falls were defined as any report of falls on the UPDRS or the adverse event log. We assessed the frequency of falls overall and by age. The relationship between prespecified fall risk markers and the probability of falling was assessed using logistic and multiple logistic regression. A hurdle Poisson model was used to jointly model the probability of remaining fall-free and the number of falls. RESULTS: During the follow-up period, 23% of participants fell, and 11% were habitual fallers. In a multiple logistic regression model, age, baseline UPDRS Falling score, and baseline PDQ-39 scores were associated with subsequent fall risk (p < 0.001). Similarly, in a hurdle Poisson regression model, age, baseline UPDRS falling item, and baseline PDQ-39 were all significantly related to the probability of falling, but only UPDRS falling >0 was associated with the number of falls. CONCLUSION: Falls are frequent and are associated with impaired quality of life, even in early PD. Current standard rating scales do not sufficiently explain future fall risk in the absence of a prior fall history. New assessment methods for falls and postural instability are required to better evaluate this important problem in clinical trials and clinical practice.

Promoting adherence to an electronic home spirometry research program after lung transplantation.

Adherence with any long-term treatment or research protocol is a challenge; this has been found to be the case with lung transplant recipients participating in an electronic home spirometry research program. Because the purpose of the current study is to develop a system for detecting early infection and rejection in lung transplant recipients, regular transmission of data by subjects to the research data center is imperative to the success of the study. Various adherence-promoting strategies have been developed by the research team to increase subject adherence with the program. An increased adherence rate has been reported after implementation of these various strategies, yet work remains to promote continually regular participation in the program by all subjects. It remains a challenge for the research team to devise creative and effective strategies for increasing adherence to regular spirometer use to provide data to develop a computerized system for detecting early infection and rejection of transplanted lung tissue.

PCR ribotyping and endonuclease subtyping in the epidemiology of Burkholderia cepacia infection.

Because of conflicting data about hospital-based transmission of Burkholderia (Pseudomonas) cepacia, an important respiratory pathogen in cystic fibrosis (CF), we compared strains found in sputum, lung, or blood of 29 CF patients in our center from 1988 to 1994, studying the relationship between strain and hospital exposure of incident and that of prevalent cases. Exposure was defined as a concurrent hospital stay between a prevalent and an incident case. B. cepacia strains were determined by polymerase chain reaction (PCR) ribotyping and endonuclease subtyping. The 16S to 23S spacer regions of the bacterial ribosomal RNA (rRNA) genes were amplified by PCR, and the product-size patterns used to type each B. cepacia isolate. Endonuclease digestion of the PCR products provided length polymorphisms for subtyping. There were 17 incident events during the period from 1988 to 1994, 16 of which involved a single ribotype. These 16 ribotypes could be divided into five subtypes by endonuclease mapping. Four patients grew B. cepacia from the blood, with the organism being the same strain as found in the lung in each case. Case controls were obtained to evaluate risk factors for B. cepacia acquisition. Concurrent hospitalization with a prevalent case significantly increased the risk of acquisition. There was no association between length of hospitalization, length of exposure, or FEV1 and the risk of B. cepacia acquisition.

Monitoring progress after lung transplantation from home-patient adherence.

A paperless electronic spirometer/diary instrument has been employed in a home monitoring programme for lung and heart-lung transplant patients at the University of Minnesota. The monitoring programme is part of a long term study to develop a system which will detect the earliest signs of developing rejection or infection in the transplanted organs. It is based on patient daily self-measurements of standard spirometry, vital signs, and symptoms recorded at home and transmitted weekly to the study data center over the telephone using a modern built into the instrument. This report summarizes adherence behaviour for 41 subjects enrolled in the study over a 12 month period. The number of subjects from whom home data has been received each week was used to measure adherence at the subject level. The number of records received each week measured adherence at the daily recording level. A data record consists of a daily set of spirometry, vital signs, and symptom values from a given subject. Approximately 82% of subjects transmitted records each week, over the 52 week review period. There was an average of 4.5 records received each week from each subject. Transmitted records had missing vital sign or symptom items in less than 2% of cases, spirometry data was always present. This evaluation showed than lung transplant recipients are willing and able to use a home-monitoring instrument, and that basic spirometry, data entry, and data transmission can be performed satisfactorily.

Clinical significance of the recovery of Aspergillus species from the respiratory secretions of cystic fibrosis patients.

The frequent recovery of Aspergillus species from the respiratory tract secretions of cystic fibrosis (CF) patients is well recognized, and the presence of the fungus in the airways may trigger an inflammatory response that can manifest as the clinical entity known as allergic bronchopulmonary aspergillosis (ABPA). In our CF patient population we studied the clinical characteristics of those who had Aspergillus sp. recovered from their respiratory tract secretions (n = 45) and compared them with the characteristics seen, during the same time period, in those patients who were culture negative for Aspergillus sp. (n = 167). There were no differences in peripheral blood eosinophil count (P = 0.9) or serum immunoglobulin E levels (P = 0.61). By logistic regression analysis there seemed to be an increased risk for more advanced lung disease, both radiographically (defined by a Brasfield chest radiograph score < 18) and by lung function parameters in those who were culture positive. However, after appropriate adjustment, almost all the increased risk was associated with age and gender, but not with the presence of Aspergillus sp. in respiratory secretions. Additionally, increasing age was strongly correlated with the risk of Aspergillus sp. being cultured from respiratory secretions (P = 0.0025). The presence of Aspergillus sp. in respiratory secretions was not associated with two indicators of atopy in our CF patient population. We do not have evidence that the culture of Aspergillus sp. from CF respiratory secretions is independently associated with an increased risk for more advanced lung disease.

Cystic fibrosis-associated colitis and fibrosing colonopathy.

OBJECTIVE: To describe our experience with cystic fibrosis (CF)-associated colitis and fibrosing colonopathy, and to assess treatment strategies. STUDY DESIGN: We reviewed hospital charts and autopsy reports of all University of Minnesota patients with CF between 1975 and August 1994. We identified six patients with colonopathy and compared them with a cohort of 79 patients with CF in the same age range and seen during the same period. RESULTS: All patients with colonopathy had bloody diarrhea; five of the six had abdominal pain. Stool frequency and related symptoms distinguished the patients with colonopathy from the cohort population. All took a higher median dose of pancreatic enzymes than the cohort population during the 3 months preceding the onset of symptoms (p < 0.002). For all six patients, barium studies revealed loss of haustration, and shortening and diffuse narrowing of the colonic lumen with relative rectal sparing. The distal ileal mucosa was irregular in four patients. A histopathologic study reveal fibrosis of the submucosa or lamina propria, and focal acute cryptitis in all six patients. Other features included ascites (2/6) and nodular regenerative hyperplasia of the liver (1/6). One patient continues to have symptoms, three had subtotal colectomy, and the condition of two improved after a regimen including a low-fat diet, withholding of pancreatic enzymes, and supplemental parenteral nutrition was initiated. CONCLUSIONS: Fibrosing colonopathy represents a newly recognized gastrointestinal complication of cystic fibrosis. Affected persons have taken larger doses of pancreatic enzymes than similar patients with cystic fibrosis, and have bloody diarrhea. We developed a medical protocol that may avoid surgical resection of the colon in some of these patients.

Contrasting clinical and statistical significance within the research setting.

When designing a clinical trial or study, the value of the following interrelated parameters should be determined prior to collecting data: clinical significance, statistical significance, power, and sample size. Too often, clinical importance and the other design issues are ignored and only statistical significance dictates the conclusions of the study. In order to evaluate the frequency that each of these design parameters is addressed in the published literature, the topic of pulmonary function tests (specifically forced vital capacity) was chosen, and all relevant articles for one year (1990) were identified using Minnesota MEDLINE. A total of 121 articles met the selection criteria and were reviewed. Of all the articles, 13.2% discussed clinical significance, 21.5% discussed sample size, and only 5.0% addressed statistical power. As expected, the majority of the articles (92.6%) discussed statistical significance (P values). None of the articles mentioned all four factors. When choosing the level of clinical significance several methods may be used. Such might be well established in certain clinical areas or available from previous publications and references or they may be attainable from pilot study data and, in the absence of any prior information, a clinician may use personal experience. To minimize subjectivity, the clinical effect-size can be based on the population distribution of the measurement of interest.

Reliability and validity of spirometry measurements in a paperless home monitoring diary program for lung transplantation.

OBJECTIVE: To demonstrate that home spirometry measurements are reliable and valid and can be used as part of a home measurement monitoring system by lung transplant recipients. DESIGN: Longitudinal, observational. SETTING: University medical center. SUBJECTS: Eighteen patients who have undergone lung transplantation; age range was 24 to 63 years (mean of 49.5 years). OUTCOME MEASURES: Reliability and validity of forced expiratory volume at 1 second (FEV1) and forced vital capacity (FVC). INTERVENTION: Recording of spirometry, vital signs, and symptom measures at home each day by use of a paperless electronic diary/spirometer instrument. RESULTS: Day-to-day variability as measured by the standard deviation ranged from 0.013 L to 0.202 L for FVC and 0.015 L to 0.117 L for FEV1. The correlation between the two best forced expiratory maneuvers on any given day was 0.98 for both FVC and FEV1, with percent differences between the measurements of 2% for FVC and 3% for FEV1. The correlation between measurements performed in the pulmonary function laboratory and measurements done by the patient at home on the same day was 0.94 for FVC and 0.99 for FEV1. CONCLUSIONS: This evaluation demonstrated that home measurements are both reliable (i.e., repeatable) and valid when compared with the "gold standard" of the pulmonary function laboratory. The home monitoring program has been well accepted by patients, is easy to use, and provides data comparable to that collected during clinic visits.

Prognostic implications of initial oropharyngeal bacterial flora in patients with cystic fibrosis diagnosed before the age of two years.

To evaluate the significance of early bacteriologic findings in infants and younger children with cystic fibrosis, we divided patients identified at < or = 2 years of age into groups by initial oropharyngeal culture: group NF, normal respiratory flora (n = 17); group SA, Staphylococcus aureus without Pseudomonas aeruginosa (n = 20); group PA, P. aeruginosa without S. aureus (n = 6); group PA/SA, P. aeruginosa and S. aureus (n = 7); and group O, other potentially pathogenic bacteria (n = 31). Follow-up of patients ranged in age from 5.4 to 13 years. At diagnosis, group PA/SA had lower Brasfield scores (p < 0.02) and higher gamma-globulin levels (p < 0.03) than the other groups. Five years after diagnosis, Brasfield scores were significantly lower in groups PA and PA/SA compared with the other groups; mean gamma-globulin levels did not differ significantly among the groups. Groups PA and PA/SA also had evidence of significantly greater obstructive pulmonary disease by spirometry than groups NF and O. Group PA/SA had a 10-year survival estimate of 57%, significantly lower than the 92% to 100% estimates of the other four groups (p < 0.0001). Thus P. aeruginosa in initial oropharyngeal cultures from patients < or = 2 years of age with cystic fibrosis was associated with significantly increased morbidity, and the finding of P. aeruginosa and S. aureus together in initial oropharyngeal cultures with a significantly increased mortality rate during the first 10 years after diagnosis.

The impact of home monitoring and daily diary recording on patient status in cystic fibrosis.

An experimental home monitoring system for assessing the progress and planning changes in the care of patients with cystic fibrosis (CF) has been implemented at the University of Minnesota Cystic Fibrosis Center. One group of patients and families did daily recording of physical measurements and symptoms, and sent the diary to the data coordinating center weekly for analysis. The remaining patients were not part of the home monitoring program. Twenty-five patients were randomly selected from the home monitoring group. They were compared to an age- and sex-matched control group not doing home monitoring to ascertain if home self-measurement and daily diary recording, in the absence of any therapeutic intervention, produced any change in physical or psychological status, pulmonary function, or growth over a 4-year study period. Subjects ranged in age from 6 to 43 years. Clinical status was measured by the National Institutes of Health cystic fibrosis scoring system. Pulmonary function was assessed as percent of predicted forced vital capacity and percent of predicted forced expiratory volume in 1 sec (FEV1). Growth was analyzed as percent of predicted weight based on age-, sex-, and height-dependent equations. Psychological status was determined by self-assessment and referral for conseling. Only percent predicted FEV1 in the control group declined significantly. There were no statistically significant changes in any other measures either within or between diary and nondiary groups over the 4-year period.(ABSTRACT TRUNCATED AT 250 WORDS)

A medical information relational database system (MIRDS).

A medical information relational database system (MIRDS) which is resident on a relational database machine and is accessed via microcomputers has been created for a pediatric pulmonary division of a research hospital. The power and flexibility of MIRDS has permitted the integration of clinical tasks, research interests, and laboratory functions. Procedures have been devised to assure data integrity, allow flexibility in data retrievals, produce standardized report formats, and permit data access for users with a wide range of query expertise. There are few impediments to the integration of additional clinical, research, and laboratory functions as the system evolves.

Implementation of a home-based program for early detection of clinical deterioration in cystic fibrosis.

A statistical decision-making system, based on daily self measurements obtained at home, has been developed that will predict the clinical status of a patient with cystic fibrosis (CF). The data for the study were collected from patients randomly selected from those served by the University of Minnesota CF Center. Participants recorded four daily measurements (weight, vital capacity, breathing rate, and resting pulse) and one weekly measurement (height) and returned completed diaries to the coordinating center each week. The goal of the rule was to determine whether each patient's clinical status was deteriorating, remaining stable, or improving at the time of the most recent set of weekly measurements. This early detection and intervention criterion (EDIC) is being used in the clinical setting to aid in the management of patients with cystic fibrosis. The computer hardware and software, particularly the relational database, have provided an efficient basis for the continued use of EDIC.

Diabetes mellitus associated with cystic fibrosis.

The prevalence of overt diabetes mellitus and carbohydrate intolerance was studied in 448 patients with cystic fibrosis (CF). Insulin-dependent diabetes (IDDM) developed in 7.6% of patients (13 male and 21 female). Survival was significantly lower (P less than 0.01) in the IDDM-CF group, with fewer than 25% surviving to age 30 years, whereas nearly 60% of the nondiabetic CF population reached this age. A significant deterioration in CF clinical status, based on NIH score, became apparent 2 years before onset of overt IDDM (P less than 0.05 at 2 years prior, P less than 0.01 at IDDM diagnosis). Total glycosylated hemoglobin (HbA1) was significantly (P less than 0.001) higher for the total CF population (7.3% +/- 1.2%) than for the general non-CF population (6.5% +/- 0.7%), and in the IDDM-CF group (P less than 0.05) compared with normoglycemic CF control patients. Female patients had a higher mean HbA1 after 12 years of age than their male counterparts did (P less than 0.02). HBA1 did not predict the development of IDDM, but there was a weak inverse relationship between HbA1 and both NIH clinical score (r = -0.41, P less than 0.02) and standard pulmonary function tests (forced vital capacity, r = -0.25, P less than 0.01) in the general CF population. Therefore, impaired carbohydrate tolerance in CF is associated with progressive clinical deterioration.

A rule for the early detection of chronic changes in cystic fibrosis patient status.

A statistical decision-making system has been developed which will predict the clinical status of a patient with cystic fibrosis based on daily self measurements obtained at home. The data for the study were collected from CF patients within 7-12 years of age. Thirty-two participants recorded four daily measurements (weight, vital capacity, breathing rate, and resting pulse) and one weekly measurement (height). In addition to the 4 daily measured values, the clinical status of each patient at his/her most recent previous clinic visit was used as a predictor variable. The measured values were used as the basis for the development of a discriminant rule. The goal of the rule was to determine whether each patient's clinical status was deteriorating, stable, or improving at the time of the most recent set of weekly measurements. Three types of analysis were performed: linear discriminant analysis, quadratic discriminant analysis, and nearest neighbor. Quadratic discriminant analysis provided the best discrimination due to the differences in the covariance matrices among the populations. The rule was able to correctly classify 77% of the 103 cases in the learning set. To further evaluate the rule, both a weighted classification percentage and weighted kappa statistic were calculated for the rule. Bootstrapping was used to predict the performance of the rule on the population with results of 77% correctly classified overall.

Feasibility and compliance studies of a home measurement monitoring program for cystic fibrosis.

A home measurement monitoring system has been developed for assessing progress and planning changes in care for patients with cystic fibrosis. Daily diary recording of specified measurements, quantitative symptom data, and free text are to be used for early detection of deteriorating trends before serious complications develop. Daily measurements made at home are lung capacity, body weight, breathing rate, and pulse. The program has been in place for the past two years, and has maintained a 75-80% consistent diary response rate among the 111 patients initially committed to the program. Measurements are easy to perform, equipment design is simple and rugged, and data handling routines designed for the program using the INSIGHT clinical data base system perform satisfactorily. Checking for data entry errors and validity checks of home measurements are a regular part of the data handling activity. Patient acceptance and long-term compliance in this program agrees very favorably with reports of other diary programs in chronic disease. Diary compliance was significantly greater among younger patients and those who lived long distances from the hospital. This study has demonstrated that home monitoring is a feasible program for patients with cystic fibrosis. It presents the possibility of detecting adverse health trends earlier than is now practical, so that patients can be treated before serious complications develop, thereby preventing the large fluctuations in health status that often accompany CF.