Gila Kriegel

Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease

BACKGROUND Inhibitors of HIV-1 protease produce a rapid decrease in plasma HIV-1 RNA, with concomitant increases in CD4 T-helper lymphocyte counts. The main side-effects of the protease inhibitors currently in use include gastrointestinal disturbances, paraesthesias, hyperbilirubinaemia, and nephrolithiasis. The increasing use of these agents in patients with advanced HIV-1 infection and CD4 counts of less than 50 cells/microL may be associated with unforeseen adverse effects not observed in earlier studies of patients with higher CD4 counts. METHODS Five HIV-infected patients with baseline CD4 lymphocyte counts of less than 50 cells/mL were admitted to the Beth Israel Deaconess Medical Center (Boston, MA, USA) with high fever (> 39 degrees C), leucocytosis, and evidence of lymph-node enlargement within 1-3 weeks of starting indinavir therapy. Informed consent was obtained for studies that entailed CD4 lymphocyte counts, immunophenotyping, isolator blood cultures, and radiological scans. Biopsy samples of cervical, paratracheal, or mesenteric lymph nodes were taken for culture and pathology in four patients. FINDINGS Lymph-node biopsy samples showed that focal lymphadenitis after initiation of indinavir resulted from unsuspected local or disseminated Mycobacterium avium complex (MAC) infection. The prominent inflammatory response to previously subclinical MAC infection was associated with leucocytosis in all patients and with an increase in the absolute lymphocyte counts in four patients. Three patients with follow-up CD4 counts showed two-fold to 19-fold increases after 1-3 weeks of indinavir therapy. Immunophenotyping after therapy in two patients showed that more than 90% of the CD4 cells were of the memory phenotype. INTERPRETATION The initiation of indinavir therapy in patients with CD4 counts of less than 50 cells/mL and subclinical MAC infection may be associated with a severe illness, consisting of fever (> 39 degrees C), leucocytosis, and lymphadenitis (cervical, thoracic, or abdominal). The intense inflammatory reactions that make admission to hospital necessary may be secondary to significant numbers of functionally competent immune cells becoming available to respond to a heavy mycobacterial burden. Prophylaxis or screening for subclinical MAC infection, or both, should therefore be done before the beginning of protease-inhibitor therapy in patients with advanced HIV infection.

Risk for Valvular Heart Disease among Users of Fenfluramine and Dexfenfluramine Who Underwent Echocardiography before Use of Medication

Fenfluramine and dexfenfluramine, two appetite-suppressant medications, were withdrawn from the market in 1997 after reported associations with valvular heart disease [1-4]. Subsequent echocardiographic surveys suggested that the prevalence of valvular disease is 30% to 38% among medication users; this is substantially higher than the 1% prevalence found in normal persons [1, 5, 6]. One casecontrol study reported a prevalence of 23% among medication users compared with 1% in controls [7]. Defining risk is especially important given the potential morbidity associated with valvular heart disease. Definitive randomized, controlled studies cannot be performed. However, retrospective casecontrol and cohort studies, which are superior to uncontrolled surveys for the estimation of true risk, can be done. To estimate the risk for medication-associated valvular heart disease, we identified users of fenfluramine or dexfenfluramine who underwent echocardiography before beginning therapy with these medications and compared these echocardiograms to those obtained after therapy was discontinued. Methods Patient Selection Patients who were prescribed fenfluramine or dexfenfluramine were identified through medication records at primary care practices affiliated with two academic medical centers in Massachusetts. In general, providers selected patients for therapy on the basis of regional guidelines [8]. Eligible patients used fenfluramine or dexfenfluramine for at least 14 days and underwent echocardiography at the study institutions after 1 January 1988 but before use of diet medication. We obtained consent from physicians and patients according to a protocol approved by the institutional review boards at each study institution. Study Design Clinical data were obtained through chart review and patient interview [9]. Patients were asked about changes in cardiopulmonary symptoms and exercise tolerance by using questions from a validated instrument [10]. A cardiopulmonary examination was performed by an examiner who was blinded to the results of echocardiography. For patients who refused to undergo examination, we abstracted data from the most recent physician examination performed after completion of diet medication therapy. Echocardiography Complete echocardiograms were obtained before and after therapy. All cardiac valves were interrogated with spectral, continuous-wave, and color Doppler echocardiography from multiple views in the standard manner [11, 12] by using mainly Hewlett-Packard Sonos series ultrasonographs (Andover, Massachusetts) with 2.5- to 2.7-MHz transducers and fundamental frequency imaging. The most recent premedication and initial postmedication echocardiograms were reread in a blinded manner by one of two trained echocardiographers. Valvular Abnormalities The following criteria were used to define valvular abnormalities. Mitral or tricuspid valve: Leaflet thickening was assessed as normal, mild, moderate, or severe according to established criteria [13]. Regurgitation was graded by qualitative estimate of the composite color Doppler jet area obtained in at least two of four views and was confirmed by spectral Doppler recordings of high-velocity, holosystolic flow in the left atrium. Regurgitation was graded as trace (jet area < 2 cm2), mild (2 to 5 cm2), moderate (6 to 10 cm2), or severe (> 10 cm2) [11, 12, 14, 15]. Aortic valve: Leaflet thickening criteria were similar to those used for the mitral and tricuspid valves except that thickening could be focal or diffuse. Regurgitation was graded according to the composite jet area obtained in three views and the jet height in the outflow tract and was confirmed by spectral Doppler recordings of high-velocity, diastolic flow in the left ventricular outflow tract. Regurgitation was graded as trace (jet area 1 cm2), mild (2 to 5 cm2), moderate (6 to 10 cm2), or severe (> 10 cm2) [11, 12, 15, 16]. Pulmonic valve: Leaflet thickening criteria were similar to those for the aortic valve. Regurgitation was considered normal (jet area 2 cm2) or abnormal (>2 cm2). Outcome Measures The primary echocardiographic outcome was development of new valvular lesions meeting U.S. Food and Drug Administration (FDA) criteria (at least mild aortic regurgitation or moderate mitral regurgitation) [1] or progression of preexisting valvular disease by at least one degree of severity that also met FDA criteria. A change in severity by one degree was defined as progression from no disease to mild disease, mild disease to moderate disease, or moderate disease to severe disease. Statistical Analysis Descriptive statistics were used to characterize patients in the cohort. The percentage of weight lost was determined by using the patients nadir body weight while taking medication and baseline body weight before taking medication. Paired analysis was used to determine the presence of the primary outcome of new or worsening valvular lesions. Each patients baseline echocardiogram served as the control for any new changes. The 95% CIs were calculated according to the normal approximation of the binomial distribution. To determine the generalizability of results obtained from this cohort, we compared the characteristics (obtained by chart review) of study patients with those of a random 8% sample of patients from the two largest group practices (approximately 80% of study patients) who were prescribed fenfluramine and dexfenfluramine but did not undergo echocardiography before medication use. We also compared enrolled patients with eligible patients who declined to participate. Comparisons were made by using the Fisher exact test for categorical variables and the Wilcoxon rank-sum test for continuous variables. In addition, we analyzed the combined secondary outcome of change in cardiopulmonary symptoms and exercise tolerance or the presence of cardiopulmonary examination findings. Results Patient Enrollment Of 873 patients identified as fenfluramine or dexfenfluramine users, 76 had echocardiography before therapy was started. Physicians excluded 11 patients. Of the 65 remaining patients, 19 declined participation. Of the 46 patients included for analysis, 34 (74%) agreed to be interviewed. The investigators examined 34 (74%) patients; examination data were abstracted from the medical record for 10 of the remaining 12 patients. Patient Characteristics and Generalizability Baseline characteristics did not differ significantly between study patients and nonenrolled eligible patients (Table 1). Compared with a random sample of patients who used diet medications but did not have echocardiography before therapy for comparison, study patients were older (P < 0.001), were more likely to be hypertensive (P = 0.04), and were more likely to have coronary artery disease (P < 0.001). Table 1. Patient Characteristics* Development of Valvular Heart Disease At baseline, eight patients (17.4%) had valvular abnormalities that met FDA criteria; seven (15.2%) had such abnormalities at follow-up. Additional patients had valvular changes that did not meet FDA criteria. Two patients with previous abnormalities that met FDA criteria regressed (Table 2). Two patients with normal mitral and aortic valves developed both mild aortic and mitral thickening at follow-up, two patients developed new mild aortic thickening, and two developed new mild mitral thickening. Table 2. Patients Exhibiting Mitral Regurgitation at Baseline and Follow-up Echocardiography Of 34 patients for whom data were available, 14 (41%) reported new or worsening cardiopulmonary symptoms or exercise intolerance after using diet medications. Of 44 patients for whom physical examination data were available, 24 (54%) had a murmur and 27 (61%) had a murmur or some abnormal physical finding that may reflect valvular abnormality (such as an abnormal heart sound or pedal edema). Of the 46 study patients, 2 (4.3% [95% CI, 0.6% to 14.8%]) developed the primary outcome of new or worsening valvular disease. Both patients were female and had used fenfluramine-phentermine. Neither patient used other diet medications or serotonergic agents. The first patient, who was 52 years of age, had a bicuspid aortic valve and mild aortic regurgitation on a blindly read echocardiogram obtained 1.9 years before medication use. Her follow-up echocardiogram (obtained after 62 days of therapy) showed progression of aortic regurgitation to moderate severity and new mild mitral regurgitation. Her pulmonary artery pressure was elevated (39 mm Hg); no adequate baseline estimate was available. Clinical readings of baseline and follow-up echocardiograms differed from the blinded readings in that aortic regurgitation was read clinically as mild to moderate without interval change. The clinical and blinded readings were otherwise consistent. This patient took fenfluramine-phentermine for 307 days and reduced her initial body mass index (30.5 kg/m2) by 12%. With the exception of a heart murmur that was present before medication use, her interview and physical examination were unremarkable and did not suggest progression of valvular disease. The second patient, who was 66 years of age, had hypothyroidism. An echocardiogram obtained 8.1 years before medication use was normal. A follow-up echocardiogram (obtained after 402 days of therapy) revealed new moderate aortic regurgitation and new mild mitral valve thickening. Her pulmonary artery pressure was elevated at 38 mm Hg on follow-up (no adequate baseline estimate was available). She used fenfluramine-phentermine for 250 days and reduced her initial body mass index (38.9 kg/m2) by 16%. She declined the medical interview and examination; review of her medical record revealed a normal cardiopulmonary examination and no reports of new cardiopulmonary symptoms after medication use. When the 8 patients with FDA-defined valvulopathy before medication use were excluded, the risk for new valvular abnormalities was 2.6% (CI, 0.1% to 13.8%). Among al

The Revolving Door of Resident Continuity Practice: Identifying Gaps in Transitions of Care

BackgroundIt is well documented that transitions of care pose a risk to patient safety. Every year, graduating residents transfer their patient panels to incoming interns, yet in our practice we consistently find that approximately 50% of patients do not return for follow-up care within a year of their resident leaving.ObjectiveTo examine the implications of this lapse of care with respect to chronic disease management, follow-up of abnormal test results, and adherence with routine health care maintenance.DesignRetrospective chart reviewSubjectsWe studied a subset of patients cared for by 46 senior internal medicine residents who graduated in the spring of 2008. 300 patients had been identified as high priority requiring follow-up within a year. We examined the records of the 130 of these patients who did not return for care.Main MeasuresWe tabulated unaddressed abnormal test results, missed health care screening opportunities and unmonitored chronic medical conditions. We also attempted to call these patients to identify barriers to follow-up.Key ResultsThese patients had a total of 185 chronic medical conditions. They missed a total of 106 screening opportunities including mammogram (24), Pap smear (60) and colon cancer screening (22). Thirty-two abnormal pathology, imaging and laboratory test results were not followed-up as the graduating senior intended. Among a small sample of patients who were reached by phone, barriers to follow-up included a lack of knowledge about the need to see a physician, distance between home and our office, difficulties with insurance, and transportation.ConclusionsThis study demonstrates the high-risk nature of patient handoffs in the ambulatory setting when residents graduate. We discuss changes that might improve the panel transfer process.

Improving the Preventive Care of Asplenic Patients

the previous 3 years. Among these patients, we identified those who might be asplenic or hyposplenic by creating a subset of patients with electronic medical records problem list entries related to asplenia, sickle cell disease, and Hodgkin lymphoma. We distributed lists of patients to physicians for review and obtained information directly from patients. On the basis of their feedback, we revised our registry.

Communicate, don't litigate: The Schwartz Center Connections Program

Little is known about effective educational approaches intended to reduce malpractice risk by improving communication with patients and among multidisciplinary teams in outpatient settings in order to prevent diagnostic delays and errors. This article discusses a prospective, controlled educational intervention that aimed to open lines of communication among teams in two disciplines: identifying how and why communication lapses occur between disciplines and with patients, and articulating strategies to avert them.

Use of an electronic medical record reminder improves HIV screening

BackgroundMore than 1 in 7 patients with human immunodeficiency virus (HIV) infection in the United States are unaware of their serostatus despite recommendations of US agencies that all adults through age 65 be screened for HIV at least once. To facilitate universal screening, an electronic medical record (EMR) reminder was created for our primary care practice. Screening rates before and after implementation were assessed to determine the impact of the reminder on screening rates.MethodsA retrospective cohort analysis was performed for patients age 18–65 with visits between January 1, 2012-October 30, 2014. EMR databases were examined for HIV testing and selected patient characteristics. We evaluated the probability of HIV screening in unscreened patients before and after the reminder and used a multivariable generalized linear model to test the association between likelihood of HIV testing and specific patient characteristics.ResultsPrior to the reminder, the probability of receiving an HIV test for previously unscreened patients was 15.3%. This increased to 30.7% after the reminder (RR 2.02, CI 1.95–2.09, p < 0.0001). The impact was most significant in patients age 45–65. White race, English as primary language, and higher median household income were associated with lower likelihoods of screening both before and after implementation (RR 0.68, CI 0.65–0.72; RR 0.74, CI 0.67–0.82; RR 0.84, CI 0.80–0.88, respectively).ConclusionsThe EMR reminder increased rates of HIV screening twofold in our practice. It was most effective in increasing screening rates in older patients. Patients who were white, English-speaking, and had higher incomes were less likely to be screened for HIV both before and after the reminder.

The Effects of Resident Peer- and Self-Chart Review on Outpatient Laboratory Result Follow-up.

Purpose Performing and teaching appropriate follow-up of outpatient laboratory results (LRs) is a challenge. The authors tested peer-review among residents as a potentially valuable intervention. Method Investigators assigned residents to perform self-review (n = 27), peer-review (n = 21), or self- + peer-review (n = 30) of outpatient charts. They also compared residence performance with that of historical controls (n = 20). In September 2012, residents examined 10 LRs from April 2012 onward. A second review in November 2012 ascertained whether performing chart review improved residents’ practice behaviors. Results Initially, the least-square (LS) mean number of LRs without documentation of follow-up per resident in the self-, peer-, and self- + peer-review group was, respectively, 0.5 (SD 1.0), 1.0 (SD 1.7), and 0.9 (SD 1.3), and post intervention, this was 1.0 (SD 0.2), 0.3 (SD 0.2), and 0.6 (SD 0.2) (self- versus peer-review P = .03). Initially the LS mean follow-up time per resident in the self-, peer-, and self- + peer-review group was, respectively, 4.2 (SD 1.2), 6.9 (SD 1.4), and 5.9 (SD 1.2) days, and after the intervention, LS mean time was 5.0 (SD 0.5), 2.5 (SD 0.6), and 3.9 (SD 0.5) days (self- versus peer-review P < .01). Self-review was not associated with significant improvements in practice. Conclusions In this comparison of self- and peer-review, only residents who performed peer-review demonstrated significant improvements in their documentation practices. These findings support the use of resident peer-review in improving LR follow-up, and potentially, in other, broader resident quality improvement initiatives.

Implementation of diagnostic pauses in the ambulatory setting

Background Diagnostic errors result in preventable morbidity and mortality. The outpatient setting may be at increased risk, where time constraints, the indolent nature of outpatient complaints and single decision-maker practice models predominate. Methods We developed a self-administered diagnostic pause to address diagnostic error. Clinicians (physicians and nurse practitioners) in an academic primary care setting received the tool if they were seeing urgent care patients who had previously been seen in the past two weeks in urgent care. We used pre–post-intervention surveys, focus groups and chart audits 6 months after the urgent care visit to assess the impact of the intervention on participant perceptions and actions. Results We piloted diagnostic pauses in two phases (3 months and 6 months, respectively); 9 physicians participated in the first phase, and 16 physicians and 2 nurse practitioners in the second phase. Subjects received 135 alerts for diagnostic pauses and responded to 82 (61% response). Thirteen per cent of alerts resulted in clinicians reporting new actions as a result of the diagnostic pauses. Thirteen per cent of cases at a 6-month chart audit resulted in diagnostic discrepancies, defined as differences in diagnosis from the initial working diagnosis. Focus groups reported that the diagnostic pauses were brief and fairly well integrated into the overall workflow for evaluation but would have benefited as a real-time application for patients at higher risk for diagnostic error. Conclusion This pilot represents the first known examination of diagnostic pauses in the outpatient setting, and this work potentially paves the way for more broad-based systems and/or electronic interventions to address diagnostic error.

Transfer of Graduating Residents’ Continuity Practices.

Authors Reply: We agree with Drs. Pincavage, Ratner, and Arora that resident patients are indeed often at higher risk for missing appointments. We did not in our study look at the issue of prior behavior with respect to missed appointments, but in a sample of ten patients in our study population, six of the ten had missed several appointments in the years preceding their resident PCP’s graduation. In our practice in general, resident patients are more likely to miss scheduled appointments than faculty patients; indeed, resident patients missed 17% of appointments as compared to 7% missed appointments for faculty patients in the past year. We suspect that residents were particularly concerned about patients who missed appointments and may have explicitly listed these patients as high risk for that reason. We agree that handoffs in these patients are likely to be more risky than in patients who generally keep appointments and that special outreach efforts should be made to these patients. This is particularly problematic since the graduated residents most familiar with these at-risk patients and their medical problems are no longer available to detect missed opportunities for care such as overdue radiology studies or blood tests. We analyzed visits to our own emergency room for this sample of ten patients and found that only a single patient had an ER visit within the year after their resident’s graduation. We are unable to capture ER visits and admissions to other hospitals and agree that ER utilization would indeed be a useful variable to examine in future studies of this phenomenon. We agree that a year is a longer than desired interval for follow-up of many patients and that many of these patients should have had multiple visits during this study year. We set the year as an intentionally long period. We agree that a future study of diabetics in which there are clear guidelines for intervals of visits might indeed look at shorter intervals between visits. Finally, we were similarly intrigued with the study by Young and colleagues in which case loads were rebalanced, though note that the number of trainees in that program was much smaller. Young described 16 graduating residents having a mean of only 18–22 patients in each psychiatry resident’s case load compared to our population of 46 residents. These investigators did not report on patient retention, so it is not clear that rebalancing loads will indeed improve patient follow-up. We have attempted rebalancing of case loads to a small degree for certain target diagnoses for educational reasons, but many of our patients who do follow up return to see a different resident PCP than our assignment due to a variety of factors. We are skeptical as to whether rebalancing will improve retention unless it is coupled with early intensive outreach from a new provider.