Practice-based research: lessons from community pharmacist participants.

We designed this project to determine community pharmacists' opinions regarding the challenges and motivations of their recent participation in a pharmacy practice-based research study At the conclusion of a randomized, multicenter study, 87 community pharmacist-investigators were sent a questionnaire that explored four areas: motivating factors to participate, barriers to participation, communication tools used by study coordinators, and design issues for future studies. Fifty-eight (67%) completed questionnaires were returned. Key factors motivating participation in the study were desire to improve the profession and opportunity to learn. Time was the greatest barrier to participation. Pharmacy practice-based research has two distinct advantages. First, it translates clinical knowledge into direct application in the community. Second, it provides needed data to demonstrate the value of enhanced pharmacy practice. Thorough understanding of pharmacists' opinions is necessary to optimize the design of future studies.

Pharmaceutical care research and education project: pharmacists' interventions.

OBJECTIVES: To describe the processes of care used by community pharmacists participating in the Pharmaceutical Care Research and Education Project (PREP) in terms of drug-related problems (DRPs), pharmacists' recommendations, and status of DRPs at follow-up, and to determine characteristics associated with DRPs. DESIGN: Descriptive analysis of the treatment group from a larger randomized, controlled cluster design. SETTING: Five independent community pharmacies in Alberta. PARTICIPANTS: One hundred fifty-nine patients who were covered under Alberta Health and Wellness's senior drug benefit plan (i.e., 65 years or older), were taking three or more medications concurrently according to pharmacy records, were able to complete telephone interviews as determined by pharmacists, maintained residence in Alberta for 12 of the 15 study months, agreed to receive their prescription medications only from the study pharmacy during the study period, and provided informed consent. MAIN OUTCOME MEASURES: Frequency of DRPs, recommendations, status of DRPs, and analysis of clinical results as determined during pharmacists' follow-up care. RESULTS: In telephone surveys, patients reported taking 4.7 prescription medications per day, but pharmacists documented 8.7 prescription medications per day in their records. Pharmacists documented 559 DRPs, a mean (+/- SD) of 3.9+/-3.2 problems per patient. Approximately 39% of problems were actual DRPs, while 60% were potential DRPs. Medical conditions associated most frequently with a DRP involved the respiratory, cardiovascular, and musculoskeletal systems. The most common DRP categories were "patient requires drug therapy" or "patient requires influenza or pneumococcal vaccination." Pharmacists wrote 551 initial clinical notes using the subjective, objective, assessment, plan (SOAP) format, and they recorded 346 follow-up interventions, also using SOAP notes. Counseling, preventive consultations, and clinical monitoring represented 40% of their recommendations. In 80% of situations, the pharmacist made the recommendation directly to the patient. On follow-up, 40% of the 559 DRPs identified were resolved, controlled, or improved. Patients accepted 76% of pharmacists' recommendations, and physicians accepted 72% of pharmacists' suggested resolutions of DRPs. Pharmacists were more likely to follow up about actual DRPs, as compared with potential ones; overall, they followed up on 62% of identified DRPs. CONCLUSION: Pharmacists identified more DRPs for study patients than previous community-based, observational studies have reported. Undertreatment appears to be a prevalent DRP. Community pharmacists' recommendations to prevent and resolve DRPs were made primarily to patients and were well accepted. More follow-up was needed for all DRPs. When follow-up occurred, the DRP results generally showed improvement.

Pharmaceutical care research and education project: patient outcomes.

OBJECTIVE: To compare patients' adherence to therapy, expectations, satisfaction with pharmacy services, and health-related quality of life (HRQOL) after the provision of pharmaceutical care with those of patients who received traditional pharmacy care. DESIGN: Randomized controlled cluster design. SETTING: Sixteen community pharmacies in Alberta, Canada. PATIENTS AND OTHER PARTICIPANTS: Ambulatory elderly (> or = 65 years of age) patients covered under Alberta Health & Wellness's senior drug benefit plan and who were concurrently using three or more medications according to pharmacy profiles. INTERVENTION: Pharmacies were randomly assigned to either treatment (intervention) or control (traditional pharmacy care) groups. Patients at treatment pharmacies were recruited into the study, and pharmacists provided comprehensive pharmaceutical care services. Pharmacists at control pharmacies continued to provide traditional pharmacy care. MAIN OUTCOME MEASURES: Study participants' opinions, adherence to therapy, and scores on the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). RESULTS: Compared with those of patients receiving traditional care, treatment patients' expectations that their pharmacist would perform activities congruent with pharmaceutical care changed over the study period. Treatment patients' satisfaction with the constructs "trust," "evaluation and goal setting," and "communicates with doctor" were also positively affected. HRQOL and patient adherence were not significantly affected by pharmaceutical care interventions. CONCLUSION: Successful implementation of a pharmaceutical care practice model has the potential to increase patients' satisfaction with their pharmacists' activities and may increase patients' expectations that pharmacists will work on their behalf to assist them with their health care needs. If pharmaceutical care affects patients' HRQOL, instruments more specific than the SF-36 may be needed to detect the differences.

Using focus groups to identify barriers to drug use in patients with congestive heart failure.

STUDY OBJECTIVE: To explore barriers to adherence to drug therapy identified by patients with congestive heart failure (CHF). SETTING: University-associated heart failure clinic and a family practice clinic. PATIENTS: Twenty-six patients with CHF. INTERVENTION: Four focus group sessions. MEASUREMENTS AND MAIN RESULTS: Participants were asked to describe how their lives changed as a result of developing CHF and the challenges they face when taking drugs for the condition. In the second half of each session, participants were asked for their opinions regarding various teaching and memory aids for improving adherence with therapy. They recognized the value of these aids and often created their own when health care professionals did not supply them. Transcripts were reviewed and comments grouped to identify patient-perceived barriers to adherence. The disease placed significant limitations on lifestyle. Furosemide had dramatic effects on daily activities, and some patients altered the dosing schedule to accommodate their plans. Influences on adherence were generalized into five themes: confidence in health care providers; their own knowledge regarding the disease and drugs used to treat it; previous experience with drugs; support from family and friends; and ease of communication with health care professionals. CONCLUSION: Focus groups are an effective and efficient method to explore patients opinions of barriers to drug therapy adherence. Such information can have a direct impact on management of patients with CHF. Information gathered in this study will be used to construct a survey to measure barriers to drug adherence and design interventions to improve adherence.

Hoping to maintain a balance: the concept of hope and the discontinuation of anorexiant medications.

The secondary analysis of transcripts from a study of 9 women who used prescription anorexiant medications described in this article was conducted to discover the role that hope played in the women's weight-loss initiatives. It was found that hope grew throughout the women's weight-loss initiative but peaked once the medications were discontinued. Seven components of the concept of hope were described in the context of the women's weight-loss experiences. Characteristics of hope in women who have discontinued anorexiant medications are different than those associated with hope in other contexts. A unique pattern of hope, hoping to maintain a balance, describes the women's experiences as they strove to maintain the weight they had lost.

Tools used to help community pharmacists implement comprehensive pharmaceutical care.

OBJECTIVE: To describe the tools and processes used in the practice enhancement program (PEP) of the Pharmaceutical Care Research and Education Project to enable community pharmacists to acquire the necessary skills, knowledge, and attitudes to deliver comprehensive pharmaceutical care to elderly ambulatory patients. SETTING: Independent community pharmacies in Alberta. PRACTICE DESCRIPTION: The PEP was designed to allow self-directed learning in a problem-based environment. The intent was for pharmacists to apply the knowledge they gained to improve drug therapy outcomes. PRACTICE INNOVATION: As a systematic approach to providing care, several tools were adapted to help pharmacists execute tasks required by the nine steps of the pharmaceutical care process proposed by Helper and Strand. These tools and processes facilitated (1) self-directed learning about diseases and drugs, (2) acquisition of relevant patient data, (3) a consistent and stepwise approach to the identification and resolution of drug-related problems, (4) documentation of care provided, and (5) continuity of care. RESULTS: To help pharmacists in the PEP acquire the necessary competency to provide pharmaceutical care, they were required to use the tools and processes described herein to work up and resolve patient problems. Initially, patient problems were presented as paper cases covering a range of acute and chronic problems, including topics applicable to geriatric patients. This was followed by a practicum phase wherein patient problems represented individuals from among their clientele. CONCLUSION: The tools and processes used in the project increased community pharmacists' competency for providing pharmaceutical care, by helping them develop the needed skills, knowledge, and attitudes.

The impact of pharmacist interventions on health-related quality of life.

OBJECTIVE: To describe and evaluate pharmacy practice-based studies that include health-related quality of life (HRQL) as an outcome measure in assessments of pharmacist interventions and to recommend approaches for incorporating HRQL as a patient outcome in pharmacy practice-based intervention studies. METHODS: Citations were identified in MEDLINE, Healthstar, EMBASE, and International Pharmaceutical Abstracts from January 1988 to February 1999 using terms for health-related quality of life and pharmacist interventions. Abstracts were screened by two reviewers and articles that reported a pharmacist intervention performed with HRQL as an outcome measure were included. RESULTS: Of 689 citations identified by the literature search terms, 11 met the inclusion criteria. Nine studies contained a disease-specific focus. The SF-36, or its variations, was the only generic instrument used, and seven studies described using a disease-specific instrument. Pharmacist interventions inconsistently demonstrated positive effects on patient HRQL. DISCUSSION: Possible reasons for not detecting significant differences in HRQL include length of study period, insufficient sample size and power, selection bias, labeling effects, the type of measure applied, and lack of actual influence of pharmaceutical services on HRQL. Strategies to strengthen the design and methodologic approach, such as the reporting of effect size, are recommended. CONCLUSIONS: In order to demonstrate the positive effect of pharmaceutical services on patient health, pharmacy practice researchers should continue incorporating HRQL outcome measures, complemented by clinical, economic, and other humanistic outcome indicators.

Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP): a randomized trial design of the effect of a community pharmacist intervention program on serum cholesterol risk.

OBJECTIVE: To determine the efficacy of a program of intervention by pharmacists on lipid risk management in patients at high risk for cardiovascular events. METHODS: Randomized, multicenter (44 sites in Alberta and Saskatchewan) study of community pharmacist intervention versus usual care in 1000 patients. Patients are those at high risk of vascular events (existing atherosclerotic vascular disease, or diabetes with > or = 1 other risk factor). After obtaining consent, the pharmacist calls the Project Office to randomize. Patients allocated to intervention receive a brochure and education about cardiovascular risk factors. Pharmacists also complete a physician contact form, which lists the patient's risk factors, medications, and any recommendations. A point-of-care cholesterol test is performed, the result is discussed with the patient, and it is entered on the contact form. If appropriate, the patient is asked to see his or her primary care physician for further assessment and/or treatment, and the form is faxed to the physician. Patients are followed up at two, four, eight, 12, and 16 weeks. During follow-up visits, pharmacists provide educational reinforcement and check for primary end point occurrence. Patients allocated to usual care receive the brochure only, with minimal follow-up. The primary end point is a composite of measurement of a complete lipid panel by the physician, or addition or modification of lipid-lowering drug therapy. Substudies will evaluate economics (third-party payer and pharmacy manager perspective), patient satisfaction, and quality of life. CONCLUSIONS: SCRIP (Study of Cardiovascular Risk Intervention by Pharmacists) is a unique ongoing trial that is evaluating a community pharmacist intervention designed to optimize cholesterol risk management in patients at high risk for cardiovascular events.

Between intention and behavior: an application of community pharmacists' assessment of pharmaceutical care.

A new practice philosophy for pharmacists, pharmaceutical care, encourages pharmacists to ensure that medication-related health outcomes are optimized. However, its adoption by community pharmacists has been slow due to numerous barriers including the economic structure of retail pharmacy, interprofessional conflicts, information limitations, gaps in pharmacy training and uneven patient demand. The specific study objectives were to (1) describe self-efficacy, beliefs, evaluations and perceived behavioral control in the provision of pharmaceutical care, (2) quantify intention and behavior to provide pharmaceutical care in a period of two weeks and (3) examine the relationships between intention and behavior. A 20% sample of Alberta community pharmacists received an attitude survey followed in two weeks by a behavior survey. Both surveys were developed for this study. Of the 320 pharmacists receiving the attitude survey, 230 completed surveys were obtained (71.9%). The behavior survey was received from 182 of those completing the attitude survey (79.1%). A causal model was constructed predicting pharmaceutical care behavior/s from pharmacists' self-efficacy, beliefs, evaluations and behavioral control. Behavioral control exerted its effect upon behavior via three pathways and its direct effect on belief was strongest. The only direct predictor of behavior was self-efficacy. The chi2 measure indicated that the model was not a perfect fit (chi2 = 99.24, df = 67, p<0.006), but the goodness of fit index (0.931), adjusted goodness of fit index (0.876), and root mean squared error (0.067) fall within acceptable ranges. Thus, it appears that pharmaceutical care implementation programs which address individual factors singly in providing pharmaceutical care will not be successful. The control pharmacists' perceive over their patient care behaviors in their practice environment is critical. Programs which help pharmacists assess their work environment and determine strategies to impact or reconstruct their environments are required.

Control with anorexiant medications.

OBJECTIVE: To show why women are still seeking anorexiant medications despite current concerns over their use. DESIGN: In-depth interviews using grounded theory methodology. SETTING: Participants chose where they were to be interviewed. PARTICIPANTS: Women older than 18 years who had previously taken or were currently taking anorexiant medications for the purpose of losing weight. METHOD: Nine women completed two semistructured in-depth interviews during which they described their experiences from the time they began pharmacologic therapy for obesity until they discontinued the medications. Interview data were compiled and analyzed until saturation was reached. MAIN OUTCOME FINDINGS: Control was an important factor for the women. Their previous lack of control was due to frustration with failed dieting attempts and feeling pressure from others to lose weight. Prescription medications controlled physiologic hunger while the women sought to lose weight. Increased control over hunger and a decrease in weight gave participants confidence to continue their weight-loss efforts without the medications. Once the medications were discontinued, the women were able to maintain weight control through various lifestyle modifications. CONCLUSIONS: Anorexiant medications provide some women with a perception of control that helps them lose weight and not regain it. Health care professionals should be aware of their patients' struggles with weight loss and understand the importance of these medications for some patients.

Design and results of a group counter-detailing DUR educational program.

PURPOSE: The study objectives were to (1) design, (2) implement and (3) evaluate a multi-step educational program as an integral component of a healthcare system's activities to improve medication use quality and control drug costs. Design and implementation of the educational program were based upon established principles of changing prescriber behavior. Two classes of oral medications, antihistamines and antibiotics, were targeted. METHODS: A before-after nonequivalent comparison group design with 2 comparison groups was used for evaluation. Medication claims data from the same time period one year previously were used as historical controls. Prescribing rates, net savings and prescribers' attitudes were assessed. RESULTS: Prescribing trends in the treatment group but not comparison groups generally reflected changes consistent with the educational message. A net savings of $84 was achieved in the antihistamine program. A net loss of ($2722) was seen in the antibiotic program. Over 75 percent of prescribers agreed or strongly agreed that the educational program was an appropriate mechanism to optimize medication use. Level of exposure and practice years affected perceived knowledge gains. CONCLUSION: The group counter-detailing DUR educational program was effective in improving prescribing rates. Prescribing rate changes and economic impacts differed by therapeutic category. The entire program was well accepted among prescribers including physicians and nurse practitioners.

Assessing physician choice of nonsteroidal antiinflammatory drugs in a health maintenance organization.

OBJECTIVE: To develop a categorization scheme for grouping various nonsteroidal antiinflammatory drugs (NSAIDs) by relative safety; to develop a method to quantify the appropriateness of the initial and subsequent choices of NSAID therapy; to assess whether NSAID prescribing was consistent with the developed criteria; to examine the cost of inappropriate, acute NSAID use as defined by the established criteria. DESIGN: Retrospective drug utilization review focusing on NSAIDs. SETTING/PARTICIPANTS: Members aged > or = 18 years of a 40,000-person southeastern Michigan health maintenance organization. MAIN OUTCOME MEASURES: (1) Appropriateness of therapy using a four-level safety classification system for the NSAIDs developed by a consensus process; criteria based on safety under the assumption that any particular NSAID is equally likely to be effective when dosed appropriately; (2) evaluation of progression of NSAID therapy using the NSAID Therapy Progression Formula. RESULTS: For acute patients, almost half of the prescriptions were for ibuprofen and 33 percent were for naproxen. Ibuprofen usage accounted for 16 percent of total NSAID cost and naproxen agents accounted for over 50 percent of that cost. Potential cost savings of approximately $82,000 probably would have occurred had a 50 percent interchange rate for ibuprofen been acceptable. For chronic patients, 85 percent were treated with one or two NSAIDs; treatments were of reasonable high quality when compared by safety profiles. There was low use of ibuprofen in patients who only received one NSAID. CONCLUSIONS: NSAID usage assessment in a large population was achieved by developing a classification and scoring system based on NSAID safety; in this population, prescribing patterns were generally consistent with established criteria; however, when considering cost, improvement in initial NSAID selection for acute patients was possible.

Assessing the quality of pharmaceutical care. II. Application of concepts of quality assessment from medical care.

OBJECTIVE: To present a framework that facilitates quality assessment of pharmaceutical care (PC) so that the profession and the public may identify pharmacists in ambulatory settings who provide quality care in all aspects of the their practices. DATA SOURCES: A MEDLINE search augmented by a review of International Pharmacy Abstracts was used to identify pertinent quality assessment and pharmacy practice literature; indexing terms included quality assurance, healthcare, pharmacists, community pharmacy services, ambulatory, pharmacy, and process and outcome assessment. STUDY SELECTION: All identified quality assessments of community pharmacy practice were considered. Studies that documented the effectiveness of specific pharmacist activities and patient satisfaction were also included. DATA EXTRACTION: The literature was independently reviewed by the primary author. DATA SYNTHESIS: The structure-process-outcome paradigm is presented as a framework for quality assessment of PC. Structure should be assessed at periodic intervals because it identifies the potential for the provision of quality care. Process, the care that pharmacists provide, must be documented and linked to outcomes before either structure or process can be used to make inferences about the quality of PC. Technical and interpersonal processes should be examined. Outcomes require an interdisciplinary approach that not only considers other medical care inputs but also recognizes the psychologic, economic, and social factors that affect health status and quality of life. Process and outcome must both be assessed to distinguish the contribution of pharmacists from that of other healthcare providers. Examples of criteria are provided and a model to integrate PC within the healthcare system is discussed. CONCLUSIONS: It is pharmacists' duty to ensure that patients receive an acceptable level of PC. The structure-process-outcome paradigm provides a framework to identify and link pharmacists' processes with patients' outcomes.

Assessing the quality of pharmaceutical care. I. One perspective of quality.

OBJECTIVE: To evaluate the concept of pharmaceutical care (PC) as a standard of quality care for ambulatory pharmacy practice. DATA SOURCES: Donabedian's article on the seven pillars or characteristics of quality provides a framework for a discussion of the merits of PC as a definition of quality. A MEDLINE search augmented by a manual review of International Pharmacy Abstracts was also used to identify pertinent English-language pharmacy literature; indexing terms included quality, community pharmacy services, ambulatory, pharmacy services, and pharmacist(s). STUDY SELECTION: Representative articles and studies promoting PC were considered. DATA EXTRACTION: The literature was independently reviewed by the primary author. DATA SYNTHESIS: An interpretation of the principles of Donabedian's article was applied to PC. PC appears to be consistent with the quality characteristics of efficacy and acceptability. The effectiveness, cost-effectiveness, and efficiency of PC should be firmly established by its practitioners as barriers are eliminated and/or overcome. The pillars of optimality, equity, and legitimacy seem to be overlooked under the current definition of PC. This article contends that PC assumes an individualist definition of quality, by definition, because of its covenantal relationship with the patient. CONCLUSIONS: Quality is defined in terms of the values of individuals and society. For now, PC appears to be the appropriate standard for defining quality in pharmacy because of the importance of individual maximal benefits within our society.

Multiple partners and partner choice as risk factors for sexually transmitted disease among female college students.

Multiple sexual partners and partner choice are believed to increase the risk of sexually transmitted disease (STD), but these behaviors had not previously been assessed outside of clinical populations. In this study, a cross-sectional survey among single, white, female students in their senior year of college was conducted to measure the association between behavioral risk factors and the acquisition of self-reported STDs during college. The usable response rate was 47.2% (n = 467). The combined prevalence of chlamydial infection, gonorrhea, genital herpes, human papillomavirus (HPV) infection, syphilis, and trichomoniasis during a 3.5-year period was 11.7%. There was a strong association between number of sexual partners and having an STD: those women with 5 or more sexual partners were 8 times more likely to report having an STD than those with only 1 partner, even after adjusting for age at first intercourse (odds ratio = 8.1; 95% confidence interval = 1.99, 32.64). The prevalence of a history of STDs increased with more causal partner choice and earlier age at first intercourse, but neither factor was independently associated with a history of STDs. Of the respondents, 23% always used condoms. Future research should focus on identifying ways of effectively changing high-risk sexual behavior.

PIP: In 1990, researchers analyzed data on 467 19-22 year old white female seniors at the University of Michigan to examine partner choice and other behavioral risk factors in relation to sexually transmitted diseases (STDs). 369 (79%) had had sexual intercourse. 43 (11.7%) had at least 1 STD while at the university. The most frequently reported STDs were chlamydia infection (6.3%) and genital warts (5.2%). Other STDs made up 2% of women with at least 1 STD: trichomoniasis, human papillomavirus infection, genital herpes, gonorrhea, and syphilis. Mean age at 1st intercourse stood at 17.7 years. Number of sexual partners while attending university ranged from 1 to 107 (mean 4.4). 70% had 1 partner and 33% =or5 partners. 44% had sex only within a steady relationship. 34% had sex with at least 1 casual partner and 23% with at least 1 nonsteady partner but no casual partners. 77% used condoms at least sometimes. Just 23% always used them. Students who had had an abnormal PAP smear were 8.36 times more likely to have had an STD than those without an abnormal PAP smear. The prevalence of STDs increased significantly with number of sexual partners (p.001). This was also true for chlamydia and genital warts (p.001). Prevalence of these 2 STDs rose as did the number of nonsteady and casual partners (p=.003 and p=.007, respectively). The odds ratio (OR) for women with at least 5 partners was 8.07. STD prevalence rose as the age at 1st intercourse fell (OR=2.19 for =or15 years; p=.035). The trend was similar for chlamydia (p=.002), but not so for genital warts. Even though the percentage of students who had had an STD was greatest among those with at least 1 casual partner (21.5% vs. 3.2% for only steady partners), the association was not significant. Women who always used condoms had the lowest STD prevalence (7.1%), but those who never used condoms had STDs (10.9%) less often than those who did some of the time (15.8%) or most of the time (12.3%). More research is needed to determine means to effectively change high risk sexual behavior.

A model of Staphylococcus aureus bacteremia, septic arthritis, and osteomyelitis in chickens.

We studied the occurrence, magnitude, and kinetics of bacteremia and the resultant osteomyelitis and septic arthritis in an avian model of Staphylococcus aureus infection. Thirty-day-old male broiler chicks were inoculated i.v. with 10(5), 10(6), or 10(7) cfu of strain Duntravis, a beta-hemolytic, coagulase-producing, capsular type 8 isolate from the synovial fluid of a 2-year-old black boy. Bacteremia occurred in 80%, 90%, and 100% of animals inoculated with 10(5), 10(6), or 10(7) cfu, respectively. The magnitude of bacteremia in surviving, bacteremic animals increased for 96 hours after inoculation and then decreased after a plateau phase. Osteomyelitis and septic arthritis occurred only in chicks that were continuously bacteremic. The occurrence of osteomyelitis was uniform among continuously bacteremic animals and developed 1 to 23 hours after inoculation. Chickens are susceptible to systemic infections with S. aureus. Bacteremia, osteomyelitis, and septic arthritis may be induced in healthy chickens without prior manipulations that depress their resistance.

Monophasic, glandular, synovial sarcomas and carcinomas of the soft tissues.

In soft tissues, malignant tumors with epithelial qualities are usually metastatic carcinomas. A rare, primary, soft-tissue tumor that is uniformly carcinoma-like is the monophasic, glandular, synovial sarcoma. We studied three cases of carcinoma-like neoplasms of soft tissue. In one primary tumor and two recurrent tumors of soft tissue, the histologic patterns were uniformly glandular. For the two recurrent tumors, the primary lesions were a classic, synovial sarcoma and a biphasic, synovial sarcoma with a histiocytic, stromal component. By inference, the third tumor, a primary "carcinoma" of soft tissue, may represent a de novo, monophasic, glandular, synovial sarcoma. Synovial sarcoma should be considered in the differential diagnosis of carcinoma like tumors discovered in the soft tissues.

Bacterial variants in urinary casts and renal epithelial cells.

Casts with numerous and unusually large granules were seen in the urine of a child with renal Fanconi's syndrome. When the urine sediment was sealed under a coverslip for several days, many granules changed to filamentous bacterial variants that segmented and, finally, appeared as streptococcal-like forms. When the patient's blood was cultured by a special method, bacterial variants grew consistently, and frequently reverted to parent coccal forms, although conventional cultures were negative. Variants from blood cultures had the same morphology and staining properties as granules in casts and in cystic structures found within hypertrophied renal pelvic epithelial cells. Cryptic parasitization with bacterial variants probably occurs in many nephropathies. Variants are known to produce toxins and immunogens, which could lead to mesangial and basement membrane deposits as well as to occlusive reactions in the renal microcirculation.