Publications

Like normal cellular nucleosides, the nucleoside reverse transcriptase (RT) inhibitor (NRTI) 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) has a 3'-hydroxyl moiety, and yet EFdA is a highly potent inhibitor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication with activity against a broad range of clinically important drug-resistant HIV isolates. We evaluated the anti-HIV activity of EFdA in primary human cells and in HIV-infected humanized mice. EFdA exhibited excellent potency against HIVJR-CSF in phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs), with a 50% inhibitory concentration of 0.25 nM and a selectivity index of 184,000; similar antiviral potency was found against 12 different HIV clinical isolates from multiple clades (A, B, C, D, and CRF01_AE). EFdA was readily absorbed after oral dosing (5 mg/kg of body weight) in both mice and the rhesus macaque, with micromolar levels of the maximum concentration of drug in serum (Cmax) attained at 30 min and 90 min, respectively. Trough levels were at or above 90% inhibitory concentration (IC90) levels in the macaque at 24 h, suggesting once-daily dosing. EFdA showed reasonable penetration of the blood-brain barrier in the rhesus macaque, with cerebrospinal fluid levels at approximately 25% of plasma levels 8 h after single oral dosing. Rhesus PBMCs isolated 24 h following a single oral dose of 5 mg/kg EFdA were refractory to SIV infection due to sufficiently high intracellular EFdA-triphosphate levels. The intracellular half-life of EFdA-triphosphate in PBMCs was determined to be >72 h following a single exposure to EFdA. Daily oral administration of EFdA at low dosage levels (1 to 10 mg/kg/day) was highly effective in protecting humanized mice from HIV infection, and 10 mg/kg/day oral EFdA completely suppressed HIV RNA to undetectable levels within 2 weeks of treatment.

OBJECTIVES

To describe the characteristics of home-based primary care practices: staffing, administrative, population served, care practices, and quality of care challenges.

DESIGN

Survey of home-based primary care practices.

SETTING

Home-based primary care practices in the United States.

PARTICIPANTS

Members of the American Academy of Home Care Medicine and nonmember providers identified by surveyed members.

MEASUREMENTS

A 58-item questionnaire that assessed practice characteristics, care provided by the practice, and how the quality of care that the practice provided was assessed.

RESULTS

Survey response rate was 47.9%, representing 272 medical house calls practices. Mean average daily census was 457 patients (median 100 patients, range 1-30,972 patients). Eighty-eight percent of practices offered around-the-clock coverage for urgent concerns, 60% held regularly scheduled team meetings, 89% used an electronic medical record, and one-third used a defined quality improvement process. The following factors were associated with practices that used a defined quality improvement process: practice holds regularly scheduled team meetings to discuss specific patients (odds ratio (OR)=2.07, 95% confidence interval (CI)=1.02-4.21), practice conducts surveys of patients (OR=8.53, 95% CI=4.07-17.88), and practice is involved in National Committee for Quality Assurance patient-centered medical home (OR=3.27, 95% CI=1.18-9.07). Ninety percent of practices would or might participate in quality improvement activities that would provide them timely feedback on patient and setting-appropriate quality indicators.

CONCLUSIONS

There is a substantial heterogeneity of home-based primary care practice types. Most practices perform activities that lend themselves to robust quality improvement efforts, and nearly all indicated interest in a national registry to inform quality improvement.

BACKGROUND

Palpitations are a common emergency department (ED) complaint, yet relatively little research exists on this topic from an emergency care perspective.

OBJECTIVES

We sought to describe the perceptions and clinical decision-making processes of emergency physicians (EP) surrounding patients with palpitations.

METHODS

We conducted 21 semistructured interviews with a convenience sample of EPs. We recruited participants from academic and community practice settings from four regions of the United States. The transcribed interviews were analyzed using a combination of structural coding and grounded theory approaches with ATLAS.ti, a qualitative data analysis software program (version 7; Atlas.ti Scientific Software Development GmbH, Berlin, Germany).

RESULTS

EPs perceive palpitations to be a common but generally benign chief complaint. EPs' clinical approach to palpitations, with regards to testing, treatment, and ED management, can be classified as relating to one or more of the following themes: (1) risk stratification, (2) diagnostic categorization, (3) algorithmic management, and (4) case-specific gestalt. With regard to disposition decisions, four main themes emerged: (1) presence of a serious diagnosis, (2) perceived need for further cardiac testing/monitoring, (3) presence of key associated symptoms, (4) request of other physician or patient desire. The interrater reliability exercise yielded a Fleiss' kappa measure of 0.69, indicating substantial agreement between coders.

CONCLUSION

EPs perceive palpitations to be a common but generally benign chief complaint. EPs rely on one or more of four main clinical approaches to manage these patients. These findings could help guide future efforts at developing risk-stratification tools and clinical algorithms for patients with palpitations.

BACKGROUND

Electronic referral and consultation systems are gaining popularity, but their contribution to the patient centered medical home-neighborhood framework of coordinated care delivery is not clear. We examined how specialists leverage an electronic referral and consultation system to deliver specialty care, identified determinants of high-quality electronic specialist communication and measured the impact of feedback to specialists on communication quality.

METHODS

Referral patterns were identified for 19 specialties using eReferral in the San Francisco public health care delivery system. Primary care provider (PCP) ratings of the quality (helpfulness and educational value) of consultative communication were measured. Using logistic regression, we identified determinants of high-quality specialist communication during pre-consultative exchange or virtual co-management. Predictors included: specialty and reviewer type, referral volume, percent of referrals never scheduled and time spent by reviewers on eReferral. A pre-post analysis examined the impact of feedback on communication quality.

RESULTS

The percentage of referrals immediately scheduled (27.2-82.8%) and never scheduled (7.7-59.3%) varied by specialty, with medical reviewers (vs. surgical and women׳s health) and physician reviewers (vs. nurse practitioners) scheduling fewer referrals immediately (p<0.001). Prevalence of high-quality communication was 71%, impacted by referral volume (adjusted odds ratio=0.78, 95%CI 0.68-0.88 for each additional 1000 referrals/year) and time spent per referral (1.18, 1.04-1.35 for each additional 3min).

CONCLUSIONS

Specialists can use electronic referral and consultation systems to enhance specialty care delivery with consultative communication that is highly rated by PCPs.

IMPLICATIONS

These data can inform the structure and functionality of future electronic consultation systems to maximize care coordination.

LEVEL OF EVIDENCE

III.