Use of the Location-Based Social Networking Application GRINDR as a Recruitment Tool in Rectal Microbicide Development Research

Mobile phone social networking applications such as GRINDR are potential tools for recruitment of men who have sex with men (MSM) for HIV prevention research. Demographics and sexual risk behaviors of men recruited through GRINDR and through traditional media were compared. GRINDR participants were younger (mean age 31 vs. 42, p?<?0.0001), more White identified (44 vs. 30?%, p?<?0.01), and had more sex partners in the previous 14 days (1.88 vs. 1.10, p?<?0.05) than other recruits. Email responses were less successful for enrollment than phone calls (5 vs. 50?%). This approach resulted in successful recruitment of younger and more educated, White identified MSM.     

Antithrombotic therapy in heparin-induced thrombocytopenia: guidelines translated for the clinician

Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome initiated by heparin exposure and characterized by thrombocytopenia and paradoxical thrombophilia. HIT is mediated by the formation of antibodies against the platelet factor 4/heparin complex, which leads to platelet activation, thrombin generation, and potentially fatal thrombotic sequelae. The clinical presentation of HIT is variable and can be easily overlooked. Although a number of functional and antigen-based immunoassays have been developed to detect the presence of HIT antibodies, initial diagnosis is often based on recognition of thrombocytopenia in the appropriate clinical context and later confirmed with immunologic testing. Given the serious clinical consequences of HIT, immediate cessation of heparin products and administration of non-heparin anticoagulants are crucial components of treatment. We provide a review of the clinical syndrome and practical summary of treatment recommendations from the most recent 2012 American College of Chest Physicians evidence-based guidelines for the treatment and prevention of HIT.     

Pharmacokinetic modeling as an approach to assessing the safety of residual formaldehyde in infant vaccines

Formaldehyde is a one-carbon, highly water-soluble aldehyde that is used in certain vaccines to inactivate viruses and to detoxify bacterial toxins. As part of the manufacturing process, some residual formaldehyde can remain behind in vaccines at levels less than or equal to 0.02%. Environmental and occupational exposure, principally by inhalation, is a continuing risk assessment focus for formaldehyde. However, exposure to formaldehyde via vaccine administration is qualitatively and quantitatively different from environmental or occupational settings and calls for a different perspective and approach to risk assessment. As part of a rigorous and ongoing process of evaluating the safety of biological products throughout their lifecycle at the FDA, we performed an assessment of formaldehyde in infant vaccines, in which estimates of the concentrations of formaldehyde in blood and total body water following exposure to formaldehyde-containing vaccines at a single medical visit were compared with endogenous background levels of formaldehyde in a model 2-month-old infant. Formaldehyde levels were estimated using a physiologically-based pharmacokinetic (PBPK) model of formaldehyde disposition following intramuscular (IM) injection. Model results indicated that following a single dose of 200 μg, formaldehyde is essentially completely removed from the site of injection within 30 min. Assuming metabolism at the site of injection only, peak concentrations of formaldehyde in blood/total body water were estimated to be 22 μg/L, which is equivalent to a body burden of 66 μg or <1% of the endogenous level of formaldehyde. Predicted levels in the lymphatics were even lower. Assuming no adverse effects from endogenous formaldehyde, which exists in blood and extravascular water at background concentrations of 0.1 mM, we conclude that residual, exogenously applied formaldehyde continues to be safe following incidental exposures from infant vaccines.     

Acceptability of Potential Rectal Microbicide Delivery Systems for HIV Prevention: A Randomized Crossover Trial

We assessed the acceptability of three of over-the-counter products representative of potential rectal microbicide (RM) delivery systems. From 2009 to 2010, 117 HIV-uninfected males (79 %) and females (21 %) who engage in receptive anal intercourse participated in a 6-week randomized crossover acceptability trial. Participants received each of three products (enema, lubricant-filled applicator, suppository) every 2 weeks in a randomized sequence. CASI and T-ACASI scales assessed product acceptability via Likert responses. Factor analysis was used to identify underlying factors measured by each scale. Random effects models were fit to examine age and gender effects on product acceptability. Three underlying factors were identified: Satisfaction with Product Use, Sexual Pleasure, and Ease of Product Use. For acceptability, the applicator ranked highest; however, differences between product acceptability scores were greatest among females and younger participants. These findings indicate that RM delivery systems impact their acceptability and should be considered early in RM development to enhance potential use.     

Physician performance assessment: prevention of cardiovascular disease

Given the rising burden of healthcare costs, both patients and healthcare purchasers are interested in discerning which physicians deliver quality care. We proposed a methodology to assess physician clinical performance in preventive cardiology care, and determined a benchmark for minimally acceptable performance. We used data on eight evidence-based clinical measures from 811 physicians that completed the American Board of Internal Medicine’s Preventive Cardiology Practice Improvement Module^SM to form an overall composite score for preventive cardiology care. An expert panel of nine internists/cardiologists skilled in preventive care for cardiovascular disease used an adaptation of the Angoff standard-setting method and the Dunn-Rankin method to create the composite and establish a standard. Physician characteristics were used to examine the validity of the inferences made from the composite scores. The mean composite score was 73.88 % (SD = 11.88 %). Reliability of the composite was high at 0.87. Specialized cardiologists had significantly lower composite scores (P = 0.04), while physicians who reported spending more time in primary, longitudinal, and preventive consultative care had significantly higher scores (P = 0.01), providing some evidence of score validity. The panel established a standard of 47.38 % on the composite measure with high classification accuracy (0.98). Only 2.7 % of the physicians performed below the standard for minimally acceptable preventive cardiovascular disease care. Of those, 64 % (N = 14) were not general cardiologists. Our study presents a psychometrically defensible methodology for assessing physician performance in preventive cardiology while also providing relative feedback with the hope of heightening physician awareness about deficits and improving patient care.     

Assessment of Hageman factor activation in human plasma: quantification of activated Hageman factor-C1 inactivator complexes by an enzyme- linked differential antibody immunosorbent assay

An enzyme-linked immunosorbent assay has been developed for the quantitation of activated Hageman factor-C1 inactivator (HF-C1 INH) complexes. Addition of increasing quantities of either of the major forms of activated Hageman factor (HFa or HFf) to normal plasma or to Hageman factor-deficient plasma leads to a dose-dependent increase in activated HF-C1 INH complexes. As little as 0.5 micrograms/mL of activated HF added to plasma can be detected, corresponding to activation of approximately 2% of plasma HF. The sensitivity of the assay is increased at least tenfold when complexes are formed in HF- deficient plasma, indicating competition between unactivated HF and activated HF-C1 INH complexes for binding to the antibody. Specificity is demonstrated in that addition of activated HF to hereditary angioedema plasma yields less than 1% of the activated HF-C1 INH complex formation obtained with normal plasma. Kaolin activation of HF- deficient plasma yields no detectable complex formation. Kaolin activation of prekallikrein-deficient plasma demonstrates a time- dependent increase in formation of activated HF-C1 INH complex consistent with the ability of HF in this plasma to autoactivate as the time of incubation with the surface is increased. Kaolin treatment of high-molecular weight (HMW) kininogen-deficient plasma yields an even more profound abnormality in the rate of formation of activated HF-C1 INH complexes reflecting the complex role of HMW kininogen in the initiation of contact activation. Although addition of corn inhibitor to plasma prevents activated HF-C1 INH complex formation, it does not inhibit activated HF sufficiently fast to prevent prekallikrein activation.     

Treating Legg-Perthes Disease

Treatment for Legg-Perthes disease should provide dynamic maintenance of the femoral head in the acetabulum, with the hip in moderate abduction and some internal rotation, and minimize stress of body weight on the avascular femoral head. The trilateral socket hip abduction orthosis accomplishes both goals while allowing the patient to be ambulatory and to participate in normal daily activities.     

“Sick” or “not-sick”: accuracy of System 1 diagnostic reasoning for the prediction of disposition and acuity in patients presenting to an academic ED

ObjectiveSystem 1 decision-making is fast, resource economic, and intuitive (eg, “your gut feeling”) and System 2 is slow, resource intensive, and analytic (eg, “hypothetico-deductive”). We evaluated the performance of disposition and acuity prediction by emergency physicians (EPs) using a System 1 decision-making process.MethodsWe conducted a prospective observational study of attending EPs and emergency medicine residents. Physicians were provided patient demographics, chief complaint, and vital sign data and made two assessments on initial presentation: (1) likely disposition (discharge vs admission) and (2) “sick” vs “not-sick”. A patient was adjudicated as sick if he/she had a disease process that was potentially life or limb threatening based on pre-defined operational, financial, or educationally derived criteria.ResultsWe obtained 266 observations in 178 different patients. Physicians predicted patient disposition with the following performance: sensitivity 87.7% (95% CI 81.4-92.1), specificity 65.0% (95% CI 56.1-72.9), LR+ 2.51 (95% CI 1.95-3.22), LR ? 0.19 (95% CI 0.12-0.30). For the sick vs not-sick assessment, providers had the following performance: sensitivity 66.2% (95% CI 55.1-75.8), specificity 88.4% (95% CI 83.0-92.2), LR + 5.69 (95% CI 3.72-8.69), LR ? 0.38 (95% CI 0.28-0.53).ConclusionEPs are able to accurately predict the disposition of ED patients using system 1 diagnostic reasoning based on minimal available information. However, the prognostic accuracy of acuity prediction was limited.