Faculty Bibliography

Objective. To evaluate the efficacy of tranexamic acid in the treatment of idiopathic and non-functional heavy menstrual bleeding. Design. Systematic review. Population. Women with a diagnosis of idiopathic and non-functional heavy menstrual bleeding treated with tranexamic acid. Methods. Electronic searches were conducted in literature databases up to February 2011 by two independent reviewers. We included all trials involving the efficacy of tranexamic acid for the treatment of heavy uterine bleeding. Pregnant, postmenopausal and cancer patients were excluded. Main outcome measures. Effect of tranexamic acid treatment on objective reduction of menstrual bleeding and improvement in patient quality of life. Results. A total of 10 studies met our inclusion criteria. Available evidence indicates that tranexamic acid therapy in women with idiopathic menorrhagia resulted in 34-54% reduction in menstrual blood loss. Following tranexamic acid treatment, patient's quality-of-life parameters improved by 46-83%, compared with 15-45% for norethisterone treatment. When compared with placebo, tranexamic acid use significantly decreased the blood loss by 70% in women with menorrhagia secondary to an intrauterine device (p<0.001). Limited evidence indicated potential benefit in fibroid patients with menorrhagia. No thromboembolic event was reported in all studies analyzed. Conclusions. Available evidence indicates that tranexamic acid treatment is effective and safe, and could potentially improve quality of life of patients presenting with idiopathic and non-functional heavy menstrual bleeding. Data on the therapeutic efficacy of tranexamic acid in patients with symptomatic fibroids are limited, and further studies are therefore needed.

Over 350,000 immigrants are detained by U.S. Immigration and Customs Enforcement (ICE) each year. An unknown fraction of these detainees have serious mental illnesses and are taken into ICE custody even though a criminal court has ordered them to enter inpatient mental health care. The authors report findings from 16 such cases in which they have provided advocacy over the past four years. In some cases, they were able to secure release of detainees into inpatient care in community (nonforensic) settings, which involved substantial logistical challenges. Given the well-documented concerns about securing adequate care for ICE detainees with mental illness, a logical policy change would be for ICE to allow these patients to enter court-ordered inpatient care. This move would improve care for patients and would also unburden ICE from the untenable proposition of caring for patients that the criminal justice system has deemed unfit for incarceration. (Psychiatric Services 63:377-379, 2012; doi: 10.1176/appi.ps.201100040).

BACKGROUND: Obesity is a serious disease that is associated with an increased risk of diabetes, hypertension, heart disease, stroke, and cancer, among other diseases. The United States Centers for Disease Control and Prevention (CDC) estimates a 20% obesity rate in the 50 states, with 12 states having rates of over 30%. Currently, the body mass index (BMI) is most commonly used to determine adiposity. However, BMI presents as an inaccurate obesity classification method that underestimates the epidemic and contributes to failed treatment. In this study, we examine the effectiveness of precise biomarkers and duel-energy x-ray absorptiometry (DXA) to help diagnose and treat obesity. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study of adults with BMI, DXA, fasting leptin and insulin results were measured from 1998-2009. Of the participants, 63% were females, 37% were males, 75% white, with a mean age = 51.4 (SD = 14.2). Mean BMI was 27.3 (SD = 5.9) and mean percent body fat was 31.3% (SD = 9.3). BMI characterized 26% of the subjects as obese, while DXA indicated that 64% of them were obese. 39% of the subjects were classified as non-obese by BMI, but were found to be obese by DXA. BMI misclassified 25% men and 48% women. Meanwhile, a strong relationship was demonstrated between increased leptin and increased body fat. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate the prevalence of false-negative BMIs, increased misclassifications in women of advancing age, and the reliability of gender-specific revised BMI cutoffs. BMI underestimates obesity prevalence, especially in women with high leptin levels (>30 ng/mL). Clinicians can use leptin-revised levels to enhance the accuracy of BMI estimates of percentage body fat when DXA is unavailable.

Previous studies have suggested that percutaneous coronary intervention (PCI) decreases long-term mortality in patients with silent myocardial ischemia (SMI), but whether PCI specifically decreases mortality when added to intensive medical therapy is unknown. We performed a post hoc analysis of clinical outcomes in patients in the COURAGE trial based on the presence or absence of anginal symptoms at baseline. Asymptomatic patients were classified as having SMI by electrocardiographic ischemia at rest or reversible stress perfusion imaging (exercise-induced or pharmacologic). Study end points included the composite primary end point (death or myocardial infarction [MI]); individual end points of death, MI, and hospitalization for acute coronary syndrome; and need for revascularization. Of 2,280 patients 12% (n = 283) had SMI and 88% were symptomatic (n = 1,997). There were no between-group differences in age, gender, cardiac risk factors, previous MI or revascularization, extent of angiographic disease, or ischemia by electrocardiogram or imaging. Compared to symptomatic patients, those with SMI had fewer subsequent revascularizations (16% vs 27%, p <0.001) regardless of treatment assignment and fewer hospitalizations for acute coronary syndrome (7% vs 12%, p <0.04). No significant differences in outcomes were observed between the 2 treatment groups, although there was a trend toward fewer deaths in the PCI group (n = 7, 5%) compared to the optimal medical therapy (OMT) group (n = 16, 11%, p = 0.12). In conclusion, addition of PCI to OMT did not decrease nonfatal cardiac events in patients with SMI but showed a trend toward fewer deaths. Although underpowered, given similar outcomes in other small studies, these findings suggest the need for an adequately powered trial of revascularization versus OMT in SMI patients.

OBJECTIVES: : We described self-reported skin rash 2 to 3 and 5 to 6 years after 9/11 and examined its association with exposures to 9/11 dust/debris. METHODS: : We analyzed a longitudinal study of New York City World Trade Center Health Registry participants who resided or worked in Lower Manhattan or worked in rescue/recovery in two surveys (W1 and W2). RESULTS: : Among 42,025 participants, 12% reported post-9/11 skin rash at W1, 6% both times, 16% at W2. Among participants without posttraumatic stress disorder or psychological distress, W1 self-reported post-9/11 skin rash was associated with intense dust cloud exposure (adjusted odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.3 to 1.9), home/workplace damage (adjusted OR = 1.8; 95% CI, 1.4 to 2.3), and working more than 90 days (adjusted OR = 1.7; 95% CI, 1.3 to 2.2) or 31 to 90 days (adjusted OR = 1.6; 95% CI, 1.3 to 2.1) at the World Trade Center site. CONCLUSIONS: : Post-9/11 skin rash may be related to acute and long-term exposure to dust, though subjectivity of skin symptoms may bias findings.

Significant ambiguity exists in the scientific community with regard to the nomenclature of 26-hydroxylated oxysterols. Oxysterols constitute an important class of compounds that have biological roles in the regulation of cholesterol synthesis and as endogenous selective estrogen receptor modulators (SERMs). The ambiguity is attributable to deviations from clearly stated IUPAC rules and is likely to increase as more biologically active oxysterols are identified. This review provides a uniform approach to the naming of 26-hydroxylated sterols for those of current interest and for those on the horizon such as oxysterols of lanosterol that retain the unsaturation at C-24 and C-25 such as (E)-26-hydroxylanosterol. Using this molecule as a starting point, this review hopes to establish a common language to keep all investigators on the same page.

Abstract The American Diabetes Association now recommends hemoglobin A(1c) (HbA(1c)) screening for the diagnosis of diabetes. It has been reported that HbA(1c) levels underestimate glycemic levels in HIV-infected persons. We examined the performance of HbA(1c) as a screening test for diabetes in a group of HIV-infected people without diabetes. We conducted a retrospective cross-sectional cohort study among HIV-infected patients determining the sensitivity and specificity of HbA(1c) as a screening test compared to fasting blood glucose (FBG). The effect of treatment regimen on the relationship between HbA(1c) and FBG was assessed by multiple linear regressions. Twenty-two of the 395 patients included in the study were newly diagnosed with diabetes based on FBG>/=126 mg/dL. Using a cutoff of HbA(1c)>/=6.5%, HbA(1c) had a sensitivity of 40.9% and specificity of 97.5% for identification of incident diabetes. At an HbA(1c) level of 5.8% the product of sensitivity and specificity was maximized, with values of 88.8% and 77.5% respectively. Higher mean cell volume (MCV) values (p=0.02) and current use of a non-nucleoside reverse transcriptase inhibitors (NNRTIs; p=0.02) significantly increased the slope, while PI use significantly decreased the slope (p<0.001), of the linear regression of HbA(1c) compared to FBG. Tenofovir use did not significantly alter the slope or y-intercept of the line. Among HIV-infected nondiabetic patients, HbA(1c) is insensitive, although highly specific for diagnosing diabetes. Current antiretroviral (ART) use has significant and variable influence on the relationship between HbA(1c) and FBG. The use of HbA(1c) in conjunction with FBG may be the best modality to screen for diabetes.

Case Presentation: A 65-year-old female with metastatic breast cancer, glioblastoma multiforme, bilateral pulmonary emboli diagnosed 4 days prior to admission started on enoxaparin, presented with syncope. On the day of admission the patient collapsed on the street suddenly without any prodrome. She reported abdominal pain for the prior 2-3 days, no other new symptoms, and no change in her baseline fatigue. On presentation to the emergency department (Figure presented) she was afebrile with a blood pressure of 105/72, and a heart rate of 92. Her physical exam was notable for conjunctival pallor and a firm, very tender 6 centimeter mass right of the midline slightly inferior to the umbilicus. Fothergill's sign was present. Her hemoglobin was 5.7 gm/dl (it was 12 gm/dl 4 days prior to admission). On CT scan of the abdomen and pelvis a large rectus sheath hematoma (RSH) was found that extended into the preperitoneal space inferiorly, as well as into the pelvis. The patient was transfused, enoxaparin was stopped and she had a retrievable inferior vena cava (IVC) filter placed. Upon further questioning, the patient reported that she had been injecting herself with enoxaparin intramuscularly rather than subcutaneously. Discussion: RSH is an uncommon cause of abdominal pain and is usually not associated with hemodynamically significant hemorhage. It is caused by rupture of the epigastric arteries or trauma to smaller vessels in the rectus muscle often due to vigorous contraction of the abdominal wall muscles from coughing, retching or straining from constipation. In this case, repeated direct intramuscular trauma from needles as well as the effect of the enoxaparin caused the hematoma. Mortality is reported at 4% for RSH but increases to 25% when anticoagulation plays a role. The patient presented with Fothergill's sign which is a painful abdominal mass that does not cross the midline and remains palpable with rectus muscle contraction thus differentiating it from an intra-abdominal mass. In light of her short term contraindication to receiving anticoagulation, an IVC filter was placed (supported by ACC/AHA guidelines issued in April 2011). The indications for placement of IVC filters are not robustly supported by evidence with only one prospective randomized study and a large populationbased retrospective analysis serving as the basis for recommendations. Because the RSH was caused by incorrect injection of enoxaparin, I recommended attempting to reinitiate anticoagulation in a monitored setting and if tolerated, removal of the retrievable IVC filter. The patient remained hemodynamically stable with an unfluctuating hemoglobin level and was transferred to the hospital where she was receiving her oncological treatment. Conclusions: RSH is often associated with the use of anticoagulation and on occasion can cause significant hemorrhage. IVC filters have a role in protecting patients with known proximal deep venous thrombosis or pulmonary embolism who have a contraindication against the use of anticoagulation

Background: Avoidable hospital readmissions may be reflective of poor quality of inpatient healthcare and may be used as a metric to guide reimbursement rates to hospitals. Most existing risk prediction models rely on administrative databases and have poor predictive ability. Physician chart reviews are necessary to identify both the cause and preventability of a readmission. Methods: We performed a retrospective chart review of 135 patients with an unplanned (Table presented) readmission to Bellevue Hospital within 7 days of discharge from the medicine service during a six month period. Each chart was reviewed independently by two experienced attending physicians. Using an algorithm developed via a pilot study, each readmission was classified into one of five categories: (1) not medically necessary (medical necessity), (2) following a discharge against medical advice (AMA), (3) related to a deficiency in the discharge process, (4) related to poor patient adherence (patient behavior) to the discharge plan, or (5) related to a condition that was difficult to predict. The latter three categories were further subcategorized to allow for more detailed analysis. Discrepancies in classification were resolved by consensus of the four authors. Baseline demographic information was obtained for the same time frame for patients who were not readmitted within 7 days. Results: During the study period there were 265 patients who were readmitted within seven days of discharge and 3,411 patients who were not. The gender ratio was not significantly different between groups (65% male in the readmitted group versus 62% male in the not readmitted group, P = 0.47). Age was significantly lower in the readmitted group (mean = 52.9 years) as compared to the not readmitted group (56.3; P = 0.001). Median length of stay (LOS) for the initial hospitalization was longer in the readmitted group (5 days vs 3 days; P = 0.0002). For the 135 readmitted cases, there was good agreement between reviewers (84%; j 0.776). The most common category of readmission was "unpredictable" (37.8%), followed by patient behavior (22.2%), discharge process (21.5%), medical necessity (9.6%), and AMA (8.9%). Conclusions: Our novel algorithm efficiently and reproducibly classified 7-day readmissions into discreet categories. Compared to all other patients, those who were readmitted within 7 days were more likely to be younger and have a longer initial LOS. We found 62% of readmissions were attributable to physician or patient behaviors, or system failures. This categorization algorithm can be used to guide creation of risk prediction models and allows for detailed analysis of individual groups that will assist development of individualized interventions to reduce rates of avoidable readmissions

Staphylococcus aureus infections are a significant cause of morbidity and mortality in health care settings. S. aureus clinical isolates vary in the function of the accessory gene regulator (agr), which governs the expression of virulence determinants, including surface and exoproteins, while agr activity has been correlated with patient outcome and treatment efficiency. Here we describe a duplex real-time nucleic acid sequence-based amplification (NASBA) detection and quantification platform for rapid determination of agr functionality in clinical isolates. Using the effector of agr response, RNAIII, as the assay target, and expression of the gyrase gene (gyrB) as a normalizer, we were able to accurately discriminate agr functionality in a single reaction. Time to positivity (TTP) ratios between gyrB and RNAIII showed very good correlation with the ratios of RNAIII versus gyrB RNA standard inputs and were therefore used as a simple readout to evaluate agr functionality. We validated the assay by characterizing 106 clinical S. aureus isolates, including strains with genetically characterized agr mutations. All isolates with dysfunctional agr activity exhibited a TTP ratio (TTP(gyrB)/TTP(RNAIII)) lower than 1.10, whereas agr-positive isolates had a TTP ratio higher than this value. The results showed that the assay was capable of determining target RNA ratios over 8 logs (10(-3) to 10(4)) with high sensitivity and specificity, suggesting the duplex NASBA assay may be useful for rapid determination of agr phenotypes and virulence potential in S. aureus clinical isolates.