Faculty Bibliography

INTRODUCTION/BACKGROUND:Phase 2 clinical trials of tuberculosis treatment have shown that once-daily regimens in which rifampin is replaced by high dose rifapentine have potent antimicrobial activity that may be sufficient to shorten overall treatment duration. Herein we describe the design of an ongoing phase 3 clinical trial testing the hypothesis that once-daily regimens containing high dose rifapentine in combination with other anti-tuberculosis drugs administered for four months can achieve cure rates not worse than the conventional six-month treatment regimen. METHODS/DESIGN/METHODS:S31/A5349 is a multicenter randomized controlled phase 3 non-inferiority trial that compares two four-month regimens with the standard six-month regimen for treating drug-susceptible pulmonary tuberculosis in HIV-negative and HIV-positive patients. Both of the four-month regimens contain high-dose rifapentine instead of rifampin, with ethambutol replaced by moxifloxacin in one regimen. All drugs are administered seven days per week, and under direct observation at least five days per week. The primary outcome is tuberculosis disease-free survival at twelve months after study treatment assignment. A total of 2500 participants will be randomized; this gives 90% power to show non-inferiority with a 6.6% margin of non-inferiority. DISCUSSION/CONCLUSIONS:This phase 3 trial formally tests the hypothesis that augmentation of rifamycin exposures can shorten tuberculosis treatment to four months. Trial design and standardized implementation optimize the likelihood of obtaining valid results. Results of this trial may have important implications for clinical management of tuberculosis at both individual and programmatic levels. TRIAL REGISTRATION/BACKGROUND:NCT02410772. Registered 8 April 2015,https://www.clinicaltrials.gov/ct2/show/NCT02410772?term=02410772&rank=1.

Many orthodontists working on patients with cleft lip and palate (CLP) have shown great enthusiasm for presurgical infant orthopedics (PSIO) to improve surgical outcomes with minimal intervention. Even though every clinician aims to use the best treatment modality for their patients, PSIO effects can be confounded by surgical type and timing of the primary repair, as is discussed in many studies. In such cases, one should be cautious when evaluating the particular outcomes for patients with CLP since it is difficult to differentiate the sole effect of an individual surgical or orthodontic intervention. As with any treatment methodology, nasoalveolar molding (NAM) has both benefits and limitations. Commonly cited concerns with NAM, and PSIO in general, include increased cost, increased burden of care, and a negative impact on maxillary growth. However, NAM cannot be deemed as having apparent long-term negative or positive effects on skeletal or soft tissue facial growth, based on previous studies. A review of the literature suggests that NAM does not alter skeletal facial growth when compared with the samples that did not receive PSIO. Nevertheless, the published studies on NAM show evidence of benefits to the patient, caregivers, the surgeon, and society. These benefits include documented reduction in severity of the cleft deformity prior to surgery and as a consequence improved surgical outcomes, reduced burden of care on the care givers, reduction in the need for revision surgery, and consequent reduced overall cost of care to the patient and society.

BACKGROUND Takotsubo cardiomyopathy is characterized by a transient left ventricular dysfunction without obstructive coronary artery disease that mimics an acute myocardial infarction. The electrocardiogram findings of Takotsubo cardiomyopathy usually present with ST-segment elevation or depression, T-wave inversion, left bundle branch block or high-grade atrioventricular block. CASE REPORT This is a report of a case of a 58-year-old male diagnosed with Takotsubo cardiomyopathy that occurred in the setting of an acute asthma exacerbation and psychiatric exacerbation with novel electrocardiogram findings of right bundle branch block. Transthoracic echocardiogram showed a preserved ejection fraction with left ventricular apical ballooning and hyperkinesis of the basal segments. The nuclear stress test showed a fixed perfusion defect at the apical segment, but the patient refused further testing such as coronary angiography. The patient was managed medically, and a repeat echocardiogram done after 8 weeks from discharge showed a complete resolution of the apical ballooning. CONCLUSIONS It is important to recognize that patients with psychiatric illness and asthma exacerbation are predisposed to develop Takotsubo cardiomyopathy. It is also reasonable to suspect Takotsubo cardiomyopathy in the presence of new electrocardiogram findings aside from those typically seen in acute myocardial infarction, especially if it is associated with apical ballooning.

Whole genome sequencing (WGS) is replacing traditional microbiological typing methods for investigation of outbreaks in clinical settings. Here, we used a clinical microbiology laboratory core genome multilocus sequence typing (cgMLST) workflow to analyze 40 isolates of K. pneumoniae which are part of the Antimicrobial Resistance Leadership Group (ARLG) isolate collection, alongside 10 Mayo Clinic K. pneumoniae isolates, comparing results to those of pulsed-field gel electrophoresis (PFGE). Additionally, we used the WGS data to predict phenotypic antimicrobial susceptibility (AST). Thirty-one of 40 ARLG K. pneumoniae isolates belonged to the same PFGE type, all of which, alongside 3 isolates of different PFGE types, formed a large cluster by cgMLST. PFGE and cgMLST were completely concordant for the 10 Mayo Clinic K. pneumoniae isolates. For AST prediction, the overall agreement between phenotypic AST and genotypic prediction was 95.6%.

Background The prevalence of hypertension in low- and middle-income countries is rapidly increasing, with most cases undiagnosed and many poorly controlled among those diagnosed. Medication reconciliation studies from high-income countries have demonstrated a high occurrence of antihypertensive medication errors and a strong association between medication errors and inadequate blood pressure control, but data from low- and middle-income countries are lacking. Methods and Results We conducted a cross-sectional study from April to October 2018 of adult patients on pharmacologic management for known hypertension at 7 public health facilities in Kweneng East District, Botswana. Our aims included to evaluate the frequency of uncontrolled hypertension, the frequency and type of medication errors causing discrepancies between patient-reported and prescribed antihypertensive medications, and the association between medication errors and uncontrolled hypertension. Descriptive analyses and multivariable logistic regression were used. The prevalence of uncontrolled hypertension was 55% among 280 enrolled adult patients, and 95 (34%) had ≥1 medication error. The most common errors included patients taking medications incorrectly (11.1%; 31/280), patients omitting medications (7.9%; 22/280), and unfilled prescriptions caused by pharmacy stock outs (7.5%%; 21/280). Uncontrolled hypertension was significantly associated with having ≥1 medication error compared with no errors (adjusted odds ratio, 3.26; 95% CI, 1.75-6.06; P<0.001). Conclusions Medication errors are strongly associated with poor blood pressure control in this setting. Further research is warranted to assess whether medication reconciliation and other low-cost interventions addressing root causes of medication errors can improve the control of hypertension and other chronic conditions in low- and middle-income countries.

BACKGROUND:Correct interpretation of the prepubescent female genital examination is a critical skill; however, physician skill in this area is limited. OBJECTIVE:To complement the bedside learning of this examination, we developed a learning platform for the visual diagnosis of the prepubescent female genital examination and examined the amount and rate of skill acquisition. PARTICIPANTS AND SETTING/METHODS:Medical students, residents, and fellows and attendings participated in an on-line learning platform. METHODS:This was a multicenter prospective cross-sectional study. Study participants deliberately practiced 158 prepubescent female genital examination cases hosted on a computer-based learning and assessment platform. Participants assigned the case normal or abnormal; if abnormal, they identified the location of the abnormality and the specific diagnosis. Participants received feedback after every case. RESULTS:We enrolled 107 participants (26 students, 31 residents, 24 fellows and 26 attendings). Accuracy (95 % CI) increased by 10.3 % (7.8, 12.8), Cohen's d-effect size of 1.17 (1.14, 1.19). The change in specificity was +16.8 (14.1, 19.5) and sensitivity +2.4 (-0.9, 5.6). It took a mean (SD) 46.3 (32.2) minutes to complete cases. There was no difference between learner types with respect to initial (p = 0.2) or final accuracy (p = 0.4) scores. CONCLUSIONS:This study's learning intervention led to effective and feasible skill improvement. However, while participants improved significantly with normal cases, which has relevance in reducing unnecessary referrals to child protection teams, learning gains were not as evident in abnormal cases. All levels of learners demonstrated a similar performance, emphasizing the need for this education even among experienced clinicians.

Background/UNASSIGNED:Hypertension is increasingly prevalent in Uganda and its clinical management remains suboptimal across the country. Prior research has elucidated some of the factors contributing to poor control, but little is known about providers' approaches to hypertension management and perceptions of barriers to care. This is particularly true in private health care settings - despite the fact that the private sector provides a substantial and growing portion of health care in Uganda. Objective/UNASSIGNED:Our exploratory, pragmatic qualitative study aimed to examine the factors affecting the quality of hypertension care from the perspective of providers working in an urban, private hospital in Uganda. We focused on the organizational and system-level factors influencing providers' approaches to management in the outpatient setting. Methods/UNASSIGNED:We conducted interviews with 19 health care providers working in the outpatient setting of a 110-bed, private urban hospital in Kampala, Uganda. We then coded the interviews for thematic analysis, using an inductive approach to generate the study's findings. Findings/UNASSIGNED:Several themes emerged around perceived barriers and facilitators to care. Providers cited patient beliefs and behaviors, driven in part by cultural norms, as a key challenge to hypertension control; however, most felt their own approach to hypertension treatment aligned with international guidelines. Providers struggled to collaborate with colleagues in coordinating the joint management of patients. Furthermore, they cited the high cost and limited availability of medication as barriers. Conclusions/UNASSIGNED:These findings offer important strategic direction for intervention development specific to this Ugandan context: for example, regarding culturally-adapted patient education initiatives, or programs to improve access to essential medications. Other settings facing similar challenges scaling up management of hypertension may find the results useful for informing intervention development as well.