Martin Rodriguez

Clinical prediction rule for stratifying risk of pulmonary multidrug-resistant tuberculosis.

Background Multidrug-resistant tuberculosis (MDR-TB), resistance to at least isoniazid and rifampin, is a worldwide problem. Objective To develop a clinical prediction rule to stratify risk for MDR-TB among patients with pulmonary tuberculosis. Methods Derivation and internal validation of the rule among adult patients prospectively recruited from 37 health centers (Perú), either a) presenting with a positive acid-fast bacillus smear, or b) had failed therapy or had a relapse within the first 12 months. Results Among 964 patients, 82 had MDR-TB (prevalence, 8.5%). Variables included were MDR-TB contact within the family, previous tuberculosis, cavitary radiologic pattern, and abnormal lung exam. The area under the receiver-operating curve (AUROC) was 0.76. Selecting a cut-off score of one or greater resulted in a sensitivity of 72.6%, specificity of 62.8%, likelihood ratio (LR) positive of 1.95, and LR negative of 0.44. Similarly, selecting a cut-off score of two or greater resulted in a sensitivity of 60.8%, specificity of 87.5%, LR positive of 4.85, and LR negative of 0.45. Finally, selecting a cut-off score of three or greater resulted in a sensitivity of 45.1%, specificity of 95.3%, LR positive of 9.56, and LR negative of 0.58. Conclusion A simple clinical prediction rule at presentation can stratify risk for MDR-TB. If further validated, the rule could be used for management decisions in resource-limited areas.

[Risk factors associated with virologic failure in HIV- infected patients receiving antiretroviral therapy at a public hospital in Peru].

OBJECTIVE To describe clinical and biological characteristics of subjects with virologic failure who participated in the sexually transmitted diseases HIV/AIDS National Program from a Peruvian public hospital. MATERIALS AND METHODS An exploratory descriptive study was performed with data from subjects older than 18 who started high activity antiretroviral therapy (HAART) between May 2004 and December 2009 and who had a viral load control after 24 weeks of HAART. Virologic failure was defined as a viral load value above 1000 copies/mL on follow up after 24 weeks on HAART. RESULTS Of 1478 records of patients on HAART analyzed, the median age was 35 years [IQR, 29-41] and 69.6% were male. Also, virologic failure occurred in 24% and 3.7% died. Of subjects with virologic failure, 9.5% died. On multivariate analysis, age, history of antiretroviral use before starting HAART, change of antiretroviral therapy due to toxicity, opportunistic infections during HAART, level of CD4 + lymphocytes below 100 cells/ml at start of HAART, adherence and clinical stage were independently associated with virologic failure. In the group of patient with no history of antiretroviral use before starting HAART, age, opportunistic infections during HAART were associated with virologic failure. CONCLUSION This study identified factors associated with virologic failure. Further studies are needed to evaluate whether the use of these factors can help to identify prospectively patients at high risk of failure, and to design interventions aimed to reduce this risk.

Fecal Microbiota Therapy for Recurrent Clostridium difficile Infection in HIV-Infected Persons

We report 2 cases of successful use of fecal microbiota therapy (fecal transplant) for recurrent Clostridium difficile infection in HIV-infected individuals. Both patients had many recurrences despite antibiotic therapy and improved after receiving fecal microbiota from healthy donors.Recurrent Clostridium difficile infection (CDI) is a common and difficult to manage problem. The risk of recurrence after a first episode is estimated to be around 20–30%, and is even higher after second or later recurrences[1]. A disrupted fecal microbiota from previous use of antibiotics plays a major role in recurrent CDI[1]. Because of the high rate of recurrence, many different treatment alternatives have been proposed[1]. In recent years several cases of successful use of fecal microbiota therapy (FMT) in the treatment of recurrent CDI have been published, with a reported success rate over 90% [1]. Here we present what to our knowledge is the first report of FMT in HIV-infected individuals.

Evaluation of an advanced physical diagnosis course using consumer preferences methods: the nominal group technique.

Background:Current evaluation tools of medical school courses are limited by the scope of questions asked and may not fully engage the student to think on areas to improve. The authors sought to explore whether a technique to study consumer preferences would elicit specific and prioritized information for course evaluation from medical students. Methods:Using the nominal group technique (4 sessions), 12 senior medical students prioritized and weighed expectations and topics learned in a 100-hour advanced physical diagnosis course (4-week course; February 2012). Students weighted their top 3 responses (top = 3, middle = 2 and bottom = 1). Results:Before the course, 12 students identified 23 topics they expected to learn; the top 3 were review sensitivity/specificity and high-yield techniques (percentage of total weight, 18.5%), improving diagnosis (13.8%) and reinforce usual and less well-known techniques (13.8%). After the course, students generated 22 topics learned; the top 3 were practice and reinforce advanced maneuvers (25.4%), gaining confidence (22.5%) and learn the evidence (16.9%). The authors observed no differences in the priority of responses before and after the course (P = 0.07). Conclusions:In a physical diagnosis course, medical students elicited specific and prioritized information using the nominal group technique. The course met student expectations regarding education of the evidence-based physical examination, building skills and confidence on the proper techniques and maneuvers and experiential learning. The novel use for curriculum evaluation may be used to evaluate other courses—especially comprehensive and multicomponent courses.

A Middle-Age Woman with Sudden Onset Dyspnea

In this series, a clinician extemporaneously discusses the diagnostic approach (regular text) to sequentially presented clinical information (bold). Additional commentary on the diagnostic reasoning process (italics) is integrated throughout the discussion.

A 22-Year-Old Woman with Abdominal Pain

In this series, a clinician extemporaneously discusses the diagnostic approach (regular text) to sequentially presented clinical information (bold). Additional commentary on the diagnostic reasoning process (italics) is integrated throughout the discussion.

Medication Possession Ratio Predicts Antiretroviral Regimens Persistence in Peru

Objectives In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru. Design And Methods Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ≥1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ≥1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables. Results 856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies. Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99). Conclusions The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.

Symptomatic duodenal cryptococcosis in HIV-infected individuals

Gastrointestinal involvement is an uncommon manifestation of cryptococcosis and, consequently, there are very few reports that have described symptomatic duodenal involvement. We present three cases of Cryptococcus-associated duodenitis in HIV-positive patients and review the literature.

Exercises in Clinical Reasoning: Take a Time-Out and Reflect

The description suggests a subacute (less than 1 month) onset of peripheral neuropathy, although the nature of bilateral lower extremity symptoms may also refer to spinal cord or parasagittal region pathology. Many peripheral neuropathies result in both sensory and motor deficits, so additional history and examination will help reveal whether he is weak. Ataxia can also be due to cerebellar, cortical, and basal ganglia pathology, so further exploration of ataxia will need to relate this finding to peripheral neuropathy. The first goal in evaluation is to further characterize the neurologic deficits in order to narrow a broad differential diagnosis.

The Emperor’s New Clothes: Prospective Observational Evaluation of the Association between the Day 2 Vancomycin Exposure and Failure Rates among Adult Hospitalized Patients with MRSA Bloodstream Infections (PROVIDE)

Abstract Background Current guidelines recommend vancomycin (VAN) dosing to achieve AUC/MIC ratio ≥400 for patients (pts) with serious MRSA bloodstream infections (BSI), but supporting data were largely derived in single center retrospective studies. A recent study using a Bayesian approach to estimate the VAN AUC found that patients with MRSA BSI who had an AUCDAY2/MICBMD ≥ 650 or an AUCDAY2/MICETEST ≥ 320 had lower incidences of failure (Clin Infect Dis 59:666, 2014). This study prospectively evaluated if these VAN AUCDAY2/MIC targets were associated with lower incidences of failure (PROVIDE, Award number UM1AI104681, Antibacterial Resistance Leadership Group). Methods Prospective, multi-center (n = 14), observational study (2014–2106) of hospitalized adults with confirmed MRSA BSI treated with VAN ≥ 72h. Exclusion: (1) neutropenia; (2) cystic fibrosis; (3) renal replacement therapy; (4) APACHE-II score > 25; (5) previous MRSA BSI within 60 days. VAN exposures were estimated using maximum a posteriori probability procedure in ADAPT 5. MICBMD and MICETEST were performed at a central laboratory. Outcomes: failure (30-day mortality or MRSA BSI ≥ 7 days); acute kidney injury (AKI), ≥1.5 × increase in serum creatinine (Scr) among patients with a baseline SCR < 2.0mg/dl. The study was powered at 80% to detect a 17.5% difference in failure between AUCDAY2/MIC groups. Results Among the 265 evaluable patients, mean (SD) age was 61 (17) and APACHE-II was 12 (6). Endocarditis was definite/possible in 29%. The MIC50/90 by BMD and ETEST were 1/1 and 1.5/1.5mg/l, respectively. Failure occurred in 18%; 26% had AKI. Mean (SD) VAN duration was 18 (14) days. Mean (SD) AUCDAY2 was 586.9 (235.5) and 44% and 73% of patients achieved an AUCDAY2/MICBMD ≥ 650 and AUCDAY2/MICETEST ≥ 320. In the multivariate analyses (Figure 1), failure was not significantly different between AUCDAY2/MIC groups. In contrast, AKI was significantly more common in patients with an AUCDAY2/ MICETEST > = 320. Conclusion Achievement of higher VAN AUCDAY2/MIC exposures for patients with MRSA BSIs were not associated with better outcomes and were found to result in increased AKI. Clinicians should assess the benefits vs. risks of using VAN regimens that confer high AUCDAY2/MIC exposures for patients with MRSA BSIs. Disclosures T. P. Lodise Jr., allergan: Consultant, Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium; medicines company: Consultant, Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium; melinta: Consultant, Consulting fee; motif: Consultant and Scientific Advisor, Consulting fee; paratek: Consultant and Scientific Advisor, Consulting fee; nabriva: Consultant, Consulting fee; M. J. Zervos, Merck, Inc.: Investigator, Research grant; M. Scheetz, Bayer: Scientific Advisor, Consulting fee; V. Fowler Jr., Pfizer, Novartis, Galderma, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Cubist, Basilea, Affinergy, Janssen, xBiotech, Contrafect: Consultant, Consulting fee; NIH, Basilea, MedImmune, Cerexa/Forest/Actavis/Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Cubist/Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius: Grant Investigator, Research grant; Green Cross, Cubist, Cerexa, Durata, Theravance; Debiopharm: Consultant, Consulting fee; UpToDate: author on several chapters, Royalties