Publications

Despite the paradigm that the innate immune system uses nucleic acid-specific receptors to detect viruses because of a lack of other conserved features, many viruses are recognized by Toll-like receptor 2 (TLR2) and TLR4. The relevance of this recognition for antiviral immunity remains largely unexplained. Here we report that TLR2 activation by viruses led to the production of type I interferon. TLR2-dependent induction of type I interferon occurred only in response to viral ligands, which indicates that TLR2 is able to discriminate between pathogen classes. We demonstrate that this specialized response was mediated by Ly6C(hi) inflammatory monocytes. Thus, the innate immune system can detect certain non-nucleic acid features of viruses and links this recognition to the induction of specific antiviral genes.

BACKGROUND

Women of childbearing age are commonly prescribed medications by primary care providers (PCPs) that may cause birth defects if used during pregnancy.

METHODS

To identify what PCPs perceive as barriers to and potential facilitators of providing counseling to women of childbearing age when teratogenic medications are prescribed, we conducted eight focus groups with 48 PCPs recruited from four clinical settings in Pittsburgh, Pennsylvania. We explored PCPs' experiences counseling women about teratogenic medications. Each focus group was audio-recorded, transcribed, and coded using a grounded theory approach by three independent coders.

RESULTS

PCPs feel responsible for counseling women when they prescribe medications that may cause birth defects, but note difficulties identifying clinically relevant sources of information on teratogenicity. Other barriers to providing counseling include limited visit times and lack of reimbursement for preconception or teratogenic risk counseling. PCPs find it challenging to identify patients who may become pregnant and who therefore need contraceptive and/or teratogenic risk counseling. PCPs expressed a desire for online resources that could be used when explaining medication risks to patients. PCPs feel that the development of patient information materials, electronic decision support tools, clinical care systems that routinely assess patients' pregnancy risk, and changes in the reimbursement structure may facilitate counseling patients about teratogenic risks.

CONCLUSIONS

PCPs perceive themselves as playing an important role in providing their patients information on risk of medication-induced birth defects. To ensure safe prescription of teratogenic medications, PCPs suggest interventions at both the clinic and healthcare system levels.

BACKGROUND

Physicians' ratings of the appropriateness of collaboration and of receiving payment for collaboration with the pharmaceutical and medical device industries may differ.

METHODS

We administered an anonymous, cross-sectional survey to a convenience sample of faculty and postgraduate physicians from all departments within the 11 hospitals affiliated with the Mount Sinai School of Medicine in New York City and New Jersey. We examined 12 collaborations with the pharmaceutical and medical device industries using 4-point Likert scales, ranging from very appropriate to very inappropriate.

RESULTS

Surveys were distributed to physicians within 35 departments at 11 hospitals; 590 surveys were completed by physicians at 9 hospitals, yielding a 67% response rate. Physicians' assessment of appropriateness varied among the different collaborations, ranging from nearly all rating developing a drug or device (92%) and designing a drug/device trial (91%) as appropriate to fewer rating preparing a manuscript of a drug/device trial (60%) and recruiting patients for a drug/device trial (65%) as appropriate for physicians not involved in trial design. Physicians consistently rated receiving payment for collaboration as appropriate less often than they rated the collaboration itself as appropriate and ratings varied among the collaborations. For example, 81% rated receiving payment to develop a drug or device as appropriate, whereas 38% rated receiving payment to recruit patients for a drug/device trial when the physician was not involved in trial design as appropriate.

CONCLUSIONS

Physicians' broadly perceived most collaboration with the pharmaceutical and medical device industries, and of receiving payment for collaboration, as appropriate.

BACKGROUND

Although ventricular assist devices (VADs) provide effective treatment for end-stage heart failure, VAD support remains associated with significant risk for adverse events (AEs). To date there has been no detailed assessment of the incidence of a full range of AEs using standardized event definitions. We sought to characterize the frequency and timing of AE onset during the first 60 days of VAD support, a period during which clinical observation suggests the risk of incident AEs is high.

METHODS

A retrospective analysis was performed utilizing prospectively collected data from a single-site clinical database including 195 patients aged 18 or greater receiving VADs between 1996 and 2006. Adverse events were coded using standardized criteria. Cumulative incidence rates were determined, controlling for competing risks (death, transplantation, recovery-wean).

RESULTS

During the first 60 days after implantation, the most common AEs were bleeding, infection, and arrhythmias (cumulative incidence rates, 36% to 48%), followed by tamponade, respiratory events, reoperations, and neurologic events (24% to 31%). Other events (eg, hemolysis, renal, hepatic events) were less common (rates <15%). Some events (eg, bleeding, arrhythmias) showed steep onset rates early after implantation. Others (eg, infections, neurologic events) had gradual onsets during the 60-day period. Incidence of most events did not vary by implant era (1996 to 2000 vs 2001 to 2006) or by left ventricular versus biventricular support.

CONCLUSIONS

Understanding differential temporal patterns of AE onset will allow preventive strategies to be targeted to the time periods when specific AE risks are greatest. The AE incidence rates provide benchmarks against which future studies of VAD-related risks may be compared.