Parametric likelihoods for multiple non-fatal competing risks and death

Clinical trials of fatal diseases often focus on one or more non-fatal events, in addition to survival, both to characterize morbidity and to improve survival estimates. Three statistical complications are that the time to each non-fatal event and subsequent residual survival may be either positively or negatively associated, the times to death with or without an antecedent event often have very different distributions, and death may censor some of the non-fatal event times. Consequently, the overall survival time distribution is a mixture of the distributions corresponding to the possible antecedent non-fatal events. These conditions violate the usual assumptions underlying many statistical methods for analysing multivariate time-to-event data. In this paper, we consider a general parametric model for multiple non-fatal competing risks and death. The model accounts for positive or negative association between the time of each non-fatal event and subsequent survival while accommodating covariates and the usual administrative censoring. Each event time distribution is specified marginally by a three-parameter generalized odds rate model, and the time of each non-fatal event and subsequent residual survival are combined under a bivariate generalized von Morgenstern distribution. The approach is illustrated by application to two data sets from clinical trials in colon cancer and acute leukaemia.     

Somatic complaints in pediatric patients: A prospective study of the role of negative life events, child social and academic competence, and parental somatic symptoms.

This prospective study of 197 pediatric patients with chronic abdominal pain examined the role of negative family life events and several potential moderator variables (child social and academic competence, parental somatic symptoms, and child sex) in child somatic complaints 1 year after a clinic visit. Results indicated that (a) among children low in social competence at the time of the initial clinic visit, higher levels of subsequent negative life events predicted higher levels of somatic complaints at follow-up; (b) among boys in families with high levels of negative life events, those whose mothers were characterized by high levels of somatic symptoms had higher levels of somatic complaints at follow-up; and (c) children whose fathers were characterized by high levels of somatic symptoms showed higher levels of somatic complaints at follow-up, regardless of the level of life events. Possible mechanisms accounting for these findings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Laboratory diagnosis before onset and prediction of Graves'' disease

BACKGROUND: The Canadian Coronary Atherectomy Trial (CCAT) assessed, in a randomized comparison, the clinical and angiographic outcomes following atherectomy with those following balloon angioplasty for the treatment of de novo lesions in the proximal one-third of the left anterior descending artery (LAD). Although the procedural success rate was somewhat higher and the postprocedure lumen larger in patients treated with atherectomy, lumen dimensions, restenosis rates and clinical outcomes were similar in the two groups at six months. To determine whether late differences emerged between the groups, clinical follow-up was obtained at a median of 18 (range 10 to 31) months after randomization. METHODS AND RESULTS: Patients were contacted monthly by telephone for the first six months. Subsequent follow-up information was obtained in 272 (99%) of the 274 randomized patients via a clinic visit or telephone interview with the patient and/or a relative. Additional information was obtained from the referring physician as required. There were no differences in adverse events between the two groups during follow-up. In patients randomized to atherectomy compared with balloon angioplasty, death occurred in 1.5% versus 2.2% (cardiac death 0.7% versus 0.7%); myocardial infarction in 5.1% versus 5.9% (Q wave 1.5% versus 1.5%); coronary bypass surgery in 13.1% versus 12.6%; and repeat target lesion intervention in 22.6% versus 21.5%. Persistent or recurrent Canadian Cardiovascular Society class III/IV angina not treated by a further intervention was present in 1.5% versus 2.2%. The combined end-point of death or nonfatal myocardial infarction occurred in nine (6.6%) versus 11 (8.1%) patients and any adverse cardiac event in 50 (36.5%) versus 53 (39.3%). Multivariate logistic regression indicated that unstable angina, reference vessel size and preprocedure minimum lumen diameter were the only variables independently associated with adverse events. CONCLUSIONS: The initial choice of directional atherectomy or balloon angioplasty had no impact on clinical outcome over a period of 18 months in this patient population. With either technique, just over 60% of patients with proximal LAD disease experienced sustained symptomatic improvement without an adverse event following a single procedure, and 80% achieved this status following a repeat percutaneous intervention.     

An overview of statistical methods for multiple failure time data in clinical trials

In a long term clinical trial to evaluate a new treatment, quite often each study subject may experience a number of 'failures' that correspond to repeated occurrences of the same type of event or events of entirely different natures during his/her follow-up period. To obtain efficient inference procedures for the therapeutic effect over time, it is desirable to utilize those multiple event times in the analysis. In this article, we review some useful procedures for analysing different kinds of multivariate failure time data. Specifically, we discuss the two-sample problems and the general regression problems with various survival models. We also give some recommendations of appropriate procedures for each type of multiple event data structure for practical usage.     

Congenital malignant rhabdoid tumour of the gum margin

One-stop clinics are becoming increasingly popular with both patients and their general practitioners. Traditionally, vascular patients have needed to attend hospital two or three times for clinical examination and investigations. We have introduced a one-stop clinic for patients with lower limb arterial disease (LLAD) and aortic aneurysms. In 92 clinics over 2 years, 1194 new patients and 1409 follow-up patients were seen, with LLAD being the largest single category comprising 40% of the patients seen, followed by varicose veins (25%), carotid disease (12%), and aortic aneurysms (8%). Overall, 57% of patients had non-invasive imaging performed, either in the clinic or on a separate visit. Performing all LLAD and aortic scans in the clinic requires 1.9 h of imaging time per clinic. Extending in-clinic scanning to patients with varicose veins and carotid disease would increase this to 3.9 h of scanning per clinic and require a duplex scanner and an additional technologist in the clinic.     

Selective and rapid uptake of adeno-associated virus type 2 in brain

Quality of life (QL) assessments are increasingly being included in clinical trials, but their use in clinical practice is still uncommon. The objectives of this study were to investigate the feasibility of introducing individual QL assessments into the daily routine of an out-patient oncology clinic, and the potential impact of such assessments on doctor-patient communication. The study sample included six physicians and 18 of their patients from the out-patient clinic of the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital in Amsterdam, The Netherlands. For each patient, three follow-up consultations were observed. The first visit was employed for the purpose of a baseline measurement. At the two subsequent visits, the patients were asked to complete the EORTC QLQ-C30, a standardised cancer-specific QL questionnaire. The patients' responses were computer-scored and transformed into a graphic summary. The summary included current scores as well as those elicited at the previous visit. Both the physicians and the patients received a copy of the summary just prior to the medical consultation. Completing, scoring and printing the QL data could be done during waiting room time. The availability of the summary did not lengthen the average consultation time. A small increase was noted in the average number of QL issues discussed per consultation. However, the most notable trend was the increased responsibility taken by the physicians in raising specific QL issues for discussion. When the QL summary was available, the physicians raised three times as many topics than was the case prior to its use (P < 0.05). All six physicians and the majority of patients believed that the QL summary facilitated communication, and expressed interest in continued use of the procedure. The introduction of individual QL assessments in routine out-patient oncology practice is feasible and appears to stimulate physicians to inquire into specific aspects of the health and well-being of their patients. However, given the methodological limitations of this pilot study, the results should be interpreted with caution.     

Comparison of patient satisfaction with ambulatory visits in competing health care delivery settings in Geneva, Switzerland

OBJECTIVES: To measure satisfaction with medical visits in various health care settings and to assess the extent to which differences in satisfaction scores between health care settings can be attributed to patients' characteristics. DESIGN: This was a cross sectional survey to measure seven dimensions of patient satisfaction. SETTINGS: Ambulatory visits to 'gatekeepers' or specialists in a newly established managed care organisation, a private group practice, or a university hospital outpatient clinic in Geneva, Switzerland. PATIENTS: There were altogether 1027 adult patients (81% participation rate). RESULTS: Patients who consulted physicians in the private group practice reported higher levels of satisfaction (overall mean 83.2 on a scale between 0 and 100) than university clinic patients (79.7), patients of independent specialists within the managed plan (78.5), and patients of managed plan gatekeepers (69.8, intergroup differences p < 0.001). Differences between settings were reduced after adjustment for sex, age, country of origin, general practitioner versus specialist visit, and scheduled versus urgent visit (adjusted scores: 80.8, 78.8, 77.6, and 72.7 in the four settings, p < 0.001). Intergroup differences were largest for general satisfaction, but small and non-significant for satisfaction with explanations given by the physician and for time spent with the patient. CONCLUSIONS: Patient satisfaction varied widely between health care settings. Differences in satisfaction ratings could be ascribed only partly to disparities in patient populations. Patients of managed plan gatekeepers were least satisfied, presumably because they could not choose their physician freely. Comparison of patient satisfaction across health care settings can provide a basis for targeted quality improvement initiatives.     

Primary care providers' responsiveness to health-risk behaviors reported by adolescent patients

OBJECTIVE: To assess clinicians' responsiveness to health-risk behaviors reported by adolescent patients during a comprehensive clinical preventive services visit. DESIGN: Nonprobability sample of adolescent patients scheduled for a routine physical examination. SETTING: Seven clinical sites in the Chicago, Ill, area. PARTICIPANTS: Fifteen primary care providers and 95 adolescent patients between 11 and 18 years of age. INTERVENTION: Providers delivered comprehensive clinical preventive services to adolescent patients using the Guidelines for Adolescent Preventive Services model. This model includes screening, guidance, a physical examination, and immunizations. Prior to the visit, adolescent patients completed a screening questionnaire that included a 52-item health-risk behavior profile. Responses on the screening questionnaire were discussed during the visit. MAIN OUTCOME MEASURES: Each provider's responsiveness to reported health-risk behaviors was determined by comparing the adolescent patient's responses on the screening questionnaire with those reported during a debriefing interview with the adolescent about whether specific subjects were discussed. Responsiveness to highly sensitive behaviors was determined by comparing the screening questionnaire and the medical record. RESULTS: On average, each adolescent patient reported 10 risk behaviors, of which 7 were discussed. The severity of the reported risk behavior, the number of reported biological health concerns, and the adolescent patient's sex were significant predictors of the provider's responsiveness. The number of reported health-risk behaviors, visit duration, provider's professional role and sex, whether the adolescent was a new patient, and the adolescent patient's age were unrelated to responsiveness. CONCLUSIONS: Providers addressed most health-risk behaviors reported during a single visit, but responsiveness declined when 3 or more biological health concerns or relatively severe problems were reported. Steps can be taken to increase providers' responsiveness.     

A Markov mixed effect regression model for drug compliance

Patient compliance (adherence) with prescribed medication is often erratic, while clinical outcomes are causally linked to actual, rather than nominal medication dosage. We propose here a hierarchical Markov model for patient compliance. At the first stage, conditional upon individual random effects and a set of individual-specific nominal daily dose times, we assume that (i) the subject-specific probability of taking zero, one, or more than one dose associated with a given nominal dose time depends on the value of certain covariates, and on the number of doses associated with the immediate previous time, but is independent of any other previous or future dosing events (the Markov hypothesis); and (ii) the set of 'errors' between actual dose times associated with each nominal time is multivariate normally distributed, conditional on covariates and the number of such actual dose times, as in (i). At the second stage, a multivariate normal distribution is assumed for the individual random effects. We fit this model by maximum likelihood to data collected over three months using an electronic system for recording actual dose times in HIV-positive patients assigned to a regimen of zidovudine thrice daily. Beyond its value for describing and quantifying compliance behaviour, as illustrated here, the model may prove useful for explanatory analyses of clinical trials.     

Long-term prognostic value of dobutamine-atropine stress echocardiography in 1737 patients with known or suspected coronary artery disease: A single-center experience

BACKGROUND: The purpose of this study was to assess the long-term value of dobutamine-atropine stress echocardiography (DSE) for prediction of late cardiac events in patients with proven or suspected coronary artery disease. METHODS AND RESULTS: Clinical data and DSE results were analyzed in 1734 consecutive patients undergoing DSE between 1989 and 1997. Seventy-four patients who underwent revascularization within 3 months of DSE and 1 patient lost to follow-up were excluded; the remaining 1659 (median age, 62 years; range, 14 to 99 years) were followed up for 36 months (range, 6 to 96 months). Wall motion abnormalities at rest and the presence and extent of stress-induced wall motion abnormalities (ischemia) were scored for each patient. Cardiac events were related to clinical and ECG data and DSE results. Four hundred twenty-eight cardiac events occurred in 366, documented cardiac death in 108 (total death, 247), nonfatal infarction in 128, and late revascularization in 192 patients. In a multivariable Cox proportional-hazards model, the ratio of documented cardiac death or (re)infarction was increased in the presence of stress-induced ischemia (hazard ratio, 3.3; 95% CI, 2.4 to 4.4) and extensive rest wall motion abnormalities (hazard ratio, 1.9; 95% CI, 1.3 to 2.6). The number of ischemic segments was predictive for late cardiac events. A normal DSE carried a relatively good prognosis, with an annual event rate of cardiac death or infarction of 1.3% over a 5-year period. CONCLUSIONS: In a large group of patients, DSE has an added value for predicting late cardiac events during long-term follow-up, improving the separation between high- risk and very-low-risk patients.     

Infant sensitivity to trajectory forms.

The authors investigated whether infants are sensitive to visual event trajectory forms, and whether they are sensitive to the underlying dynamics of trajectory forms. The authors habituated 8-month-old infants to a videotaped event run either forward or reversed in time and then switched them to the same event run in the opposite direction. Infants dishabituated when switched to the event with the novel direction in time, indicating sensitivity to the form of the trajectory. Infants exhibited equivalent habituation rates and looking times for forward and reversed events, thus failing to provide evidence that infants are sensitive to the underlying dynamics. In a partial replication of this first experiment, the same pattern of results was found. Both experiments revealed infant sensitivity to the trajectory forms, but not the underlying dynamics of events. The authors discuss implications for methods used in infant event perception studies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Optimization of hydrolysis of protein substrates by yeast proteases from Saccharomyces carlsbergenis

Maximizing efficiency of staff and resources is one method of reducing costs without affecting quality. Using a methodology similar to that used to maximize efficiency of airline-gate use, we developed a model with which to evaluate nursing support staff and clinical examining-room resources in a general otolaryngology clinic. For 144 patients over 7 consecutive clinic days, with four otolaryngologists and various combinations of support staff and examining rooms, we measured space and staff resource use, including total clinic time, number of patients seen, patient waiting time, physician and nurse productivity, and examining-room use. A simulation model was used as the medium of analysis to define parameters of the patient encounter. We identified optimal efficiency when there were three examining rooms and one and one-half nursing staff per physician or five examining rooms and three nursing staff for two simultaneously practicing physicians. Compared with a model of two rooms and one nursing staff member, our ideal model increased the percentage of the physicians' time spent in direct contact with patients from 84% to 92%. Visit length decreased from 81 minutes to 57 minutes, the average time from check-in to examination decreased from 47 to 16 minutes, and it became possible for three additional patients to be seen each day. Additional rooms and support staff, in comparison with the optimally efficient distribution, did not significantly affect these parameters. Maximizing efficiency with the use of this methodology can decrease waiting times for patients, resulting in greater patient satisfaction, improved physician productivity, total number of patients seen, and increased total contact time between physicians and patients.     

Evaluation of the quality of filling out medical records in a hypertension consultation

The aim of the study was to evaluate the completion of medical records of a hypertension clinic and to compare standardized computerized records versus standard medical records. The medical records of 163 consecutive hypertensive patients attending at the Broussais hospital hypertension clinic between December 1995, 6th and January 1996, 21st were checked. At the last visit, the patients were attended by 16 physicians working in 4 different teams. The medical data were recorded by physicians in the computerized system called ARTEMIS in 120 patients and in standard structured forms in 43 patients. The patients notes were checked to see if 9 clinical items were recorded at the first visit (V1), at the visit before last (V2) and at the last visit (V3). The overall completion rate was high at V1 (92.2%) and significantly decreased at follow-up visits (82.6% at V2 and 83.2% at V3). The completion rate was significantly higher in the computerized records than in the standard notes: 95.8% vs 82.2% at V1, 91.9% vs 56.3% at V2 and 91.6% vs 59.7% at V3. During follow-up (V2 vs V1), a significant decrease in the completion rate of 6 items was observed in the standard notes (tobacco use, alcohol consumption, physical activity, compliance to treatment, body weight, manual blood pressure measurement). In the computerized records, only physical activity completion rate decreased. In conclusion, the computer may help to increase the quality of the medical records as reflected by the completion rate of items related to hypertension care.     

Effects of EM574 and cisapride on gastric contractile and emptying activity in normal and drug-induced gastroparesis in dogs

Acute rejection episodes are thought to be prognostic of eventual kidney graft failure. The influence of rejection events on the hazard of transplant failure appears to be a complex function of how long after transplantation the rejection event occurs as well as the time elapsed since the rejection event. To examine the nature of this relationship, we propose a penalized likelihood approach to estimate the parameters of a two-dimensional rectanglewise constant hazard model. The approach appears to be fairly successful at modelling time dependency in a time-varying covariate. The approach is equally applicable for modelling fixed covariates that act in a jointly nonproportional (non-log-linear) and time-dependent manner.     

Seven zinc-finger transcription factors are expressed sequentially during the development of anthers in petunia

BACKGROUND: Little is known about the value of heart rate variability in patients with symptomatic coronary artery disease with a preserved left ventricular function. We hypothesized that in these patients heart rate variability might be a helpful adjunct to conventional parameters to predict clinical events. METHODS: In a prospective 2-year follow-up study ambulatory electrocardiographic recordings were performed in 263 consecutive male patients (mean age 56+/-8 years) with stable angina pectoris and a mean left ventricular ejection fraction of 71%+/-12%. Clinical events consisted mainly of coronary events such as percutaneous transluminal angioplasty or coronary artery bypass graft operation. RESULTS: Low measures of standard deviation of normal R-R intervals, standard deviation of the mean R-R intervals of 5 minutes, and two spectral components of heart rate variability were found in patients who had had an event compared with patients with no event. Adjusted for severity of angina, the presence of a previous myocardial infarction, and the use of beta-blockers in a logistic regression model this relation remained statistically significant for SDNN. Healthy volunteers appeared to have the highest measures of heart rate variability. CONCLUSION: In patients with ischemic heart disease and normal or near normal ventricular function decreased heart rate variability is associated with adverse clinical events.     

An optimized AV delay algorithm for patients with intermittent atrioventricular conduction

Detection and promotion of an intermittent atrioventricular (AV) conduction is the objective of an AV delay hysteresis algorithm in dual chamber pacemaker (DDD) pacing. The AV delay following an atrial event is automatically extended by a programmable interval (AV hysteresis interval) if the previous cycle showed spontaneous AV conduction, i.e., a ventricular event was detected within the previous AV delay. An automatic search mode scans for spontaneous ventricular events during the hysteresis interval: a single AV delay extension (equal to the programmed AV delay hysteresis) will occur after a successive, programmable number of AV cycles with ventricular pacing. If a spontaneous AV conduction is present, the AV delay will remain extended by the hysteresis interval. Our first results in 17 patients with intermittent AV block disclosed a satisfactorily working algorithm with effective reduction of ventricular stimuli. In relation to the underlying conduction disturbance and pacemaker settings, the majority of our patients showed a reduction of ventricular pacing events up to 90% without any adverse hemodynamic or electrophysiological changes. Based on clinical (promotion of a physiological activation and contraction sequence) and technical (reduction of power consumption) advantages, the AV hysteresis principle could be of incremental value for future dual chamber pacing in patients with intermittent complete heart block.     

Adverse events with transvenous implantable cardioverter-defibrillators: a prospective multicenter study. European 7219 Jewel ICD investigators

BACKGROUND: A newly developed classification system relates adverse events to the surgical procedure or the function of the implantable defibrillator. METHODS AND RESULTS: Adverse events were monitored during prospective clinical evaluation of the Medtronic model 7219 Jewel ICD and were classified according to the definitions of the ISO 14155 standard for device clinical trials into 3 groups: severe and mild device-related and severe non-device-related adverse events. In addition, events were related to the surgical procedure, treatment with the device, or cardiac function. Seven hundred seventy-eight patients were followed up for an average of 4.0 months after ICD implantation. In total, 356 adverse events were observed in 259 patients. At 1, 3, and 12 months after ICD implantation, 99%, 98%, and 97% of the patients, respectively, survived; 95%, 93%, and 92%, respectively, were free of surgical reintervention; and 79%, 68%, and 51%, respectively, were free of any adverse event. Twenty patients died: 6 deaths were related to the surgical procedure, 12 deaths were considered unrelated to ICD treatment, and 2 patients died of an unknown cause. Of 111 nonlethal severe adverse device effects, 47 required surgical intervention, 19 times for correction of a dislodged lead. Inappropriate delivery of therapy was observed 128 times in 111 patients, and the events were typically resolved by reprogramming or drug adjustment. Nine of these required rehospitalization. CONCLUSIONS: Approximately 50% of patients experience an adverse event within the first year after ICD implantation. The observed adverse event rate depends on the definitions and the prospective monitoring. The incidence of inappropriate therapy emphasizes the need for improved detection algorithms and for quality-of-life evaluations, especially when considering ICD treatment in high-risk but arrhythmia-free patients.     

Effects of surgical anaesthesia on the viability of nigral grafts in the rat striatum

OBJECTIVE: To compare betamethasone with placebo as an adjuvant to antibiotic therapy in the treatment of acute exudative pharyngitis. METHODS: The study was a randomized, doubled-blind, placebo-controlled, single-center, parallel, outpatient clinical trial. After consent was obtained, each patient was asked to rate his or her pain on a 10-cm numbered visual analog scale (VAS; 0-10). All of the patients received injectable benzathine penicillin. If allergic to penicillin, they were started on a 10-day course of polyenteric-coated erythromycin (PCE). Each patient was randomized to receive either i.m. betamethasone or i.m. placebo. All patients were contacted by telephone at 24 and 48 hours by one of the study investigators and asked to rate their pain based on another VAS. If their pain was not resolved by 48 hours, they were called again daily between the third and seventh days after the initial visit to determine the time of pain resolution. RESULTS: A total of 92 patients were enrolled in the study, with 46 randomized to receive placebo and 46 to receive betamethasone. Eight patients were excluded from the statistical analysis because of inability to obtain follow-up. Demographic comparison showed that gender distributions, ages, mean initial pain scores, mean times to the first and second follow-up calls, and treatment regimens were similar in the 2 groups. There were significantly better pain scores for the betamethasone group at first follow-up (p = 0.0005), at second follow-up (p = 0.004), and in number of hours until relief of pain (p = 0.004). When only those patients with a positive culture for a streptococcus species were analyzed, there also were significant reductions in pain score at the first (p = 0.006) and second (p = 0.02) follow-up visits. CONCLUSION: Pain relief was greater and more rapid in patients treated with betamethasone as an adjuvant therapy in acute exudative pharyngitis.     

Linking inpatients with schizophrenia to outpatient care

OBJECTIVE: This study focused on inpatients with schizophrenia or schizoaffective disorder who were scheduled to begin outpatient care with clinicians who had not previously treated them. The authors evaluated the effects of communication between the patients and their outpatient clinicians before discharge on patients' referral compliance, psychiatric symptoms, and community function at follow-up three months after discharge. METHODS: A total of 104 adult inpatients with schizophrenia or schizoaffective disorder who were scheduled to receive outpatient care from clinicians who had not previously treated them were evaluated at hospital discharge and again three months later. Comparisons were made between patients who had telephone or face-to-face contact with an outpatient clinician before hospital discharge and patients who did not have such contact. RESULTS: About half (51 percent) of the inpatient sample communicated with an outpatient clinician before leaving the hospital. Compared with patients who had no communication, those who spoke with an outpatient clinician were significantly more likely to complete the outpatient referral. After baseline scores and other covariates were controlled for, predischarge contact with an outpatient clinician was associated with a significantly lower total Brief Psychiatric Rating Scale score at follow-up and less self-assessed difficulty controlling symptoms. Nonsignificant trends toward improved medication compliance and a lower rate of homelessness were also found. The two patients groups did not significantly differ in the proportion who were readmitted to the hospital or who made a psychiatric emergency room visit during the follow-up period. CONCLUSIONS: Direct communication between inpatients and new outpatient clinicians may help smooth the transition to outpatient care and thereby contribute to improved control of clinical symptoms.     

Spindle cell (Kaposiform) hemangioendothelioma with Kasabach-Merritt syndrome in an infant: successful treatment with alpha-2A interferon

Typically, the primary instructional method for ambulatory care education is direct interaction between a preceptor and a learner during a patient encounter. This paper describes instructional strategies teachers and learners can use in ambulatory care training that can occur before or after scheduled clinic hours, thus providing instruction without disrupting a preceptor's busy clinic. First, they describe how preceptors and clerkship or residency-program directors can orient learners prior to their arrival at assigned sites, so that learners are better prepared to assume their patient-care responsibilities. Then they discuss strategies for making use of various types of conferences and independent learning activities to enhance learners' clinical experiences. Conferences and independent study projects that occur before clinic hours can help learners bring a higher level of thinking and clinical sophistication to their role in the ambulatory care site; conferences and independent study activities that occur after clinic hours give learners an opportunity to reinforce and expand on what they have learned during clinic. In this way, learners' educational experiences are enhanced, the best use is made of preceptors' time and expertise, and clinic efficiency is not disrupted.