Delphine S. Tuot

Two-step binding mechanism for T-cell receptor recognition of peptide-MHC

T cells probe a diverse milieu of peptides presented by molecules of the major histocompatibility complex (MHC) by using the T-cell receptor (TCR) to scan these ligands with high sensitivity and specificity. Here we describe a physical basis for this scanning process by studying the residues involved in both the initial association and the stable binding of TCR to peptide–MHC, using the well-characterized TCR and peptide–MHC pair of 2B4 and MCC-IEk (moth cytochrome c, residues 88–103). We show that MHC contacts dictate the initial association, guiding TCR docking in a way that is mainly independent of the peptide. Subsequently, MCC-IEk peptide contacts dominate stabilization, imparting specificity and influencing T-cell activation by modulating the duration of binding. This functional subdivision of the peptide–MHC ligand suggests that a two-step process for TCR recognition facilitates the efficient scanning of diverse peptide–MHC complexes on the surface of cells and also makes TCRs inherently crossreactive towards different peptides bound by the same MHC.

Awareness of Chronic Kidney Disease Among Patients and Providers

Earlier recognition of chronic kidney disease (CKD) could slow progression, prevent complications, and reduce cardiovascular-related outcomes. However, current estimates of CKD awareness indicate that both patient- and provider-level awareness remain unacceptably low. Many of the factors that are possibly associated with CKD awareness, which could help guide implementation of awareness efforts, have yet to be fully examined. Also, little is known regarding whether increased patient or provider awareness improves clinical outcomes, or whether there are possible negative consequences of awareness for CKD patients. Further research is necessary to continue to design and refine awareness campaigns aimed at both patients and providers, but there is an immediate need for dissemination of basic CKD information, given both the high prevalence of CKD and its risk factors and the low estimated awareness of CKD.

The Use of Spanish Language Skills by Physicians and Nurses: Policy Implications for Teaching and Testing

Language barriers present a substantial communication challenge in the hospital setting. To describe how clinicians with various levels of Spanish language proficiency work with interpreters or their own Spanish skills in common clinical scenarios. Survey of physicians and nurses who report ever speaking Spanish with patients on a general medicine hospital floor. Spanish proficiency rated on a 5-point scale, self-reported use of specific strategies (own Spanish skills, professional or ad-hoc interpreters) to overcome the language barrier. Sixty-eight physicians and 65 nurses participated. Physicians with low-level Spanish proficiency reported frequent use of ad-hoc interpreters for all information-based scenarios, except pre-rounding in the morning when most reported using their own Spanish skills. For difficult conversations and procedural consent, most used professional interpreters. Comparatively, physicians with medium proficiency reported higher rates of using their own Spanish skills for information-based scenarios, lower rates of professional interpreter use, and little use of ad-hoc interpreters. They rarely used their own Spanish skills or ad-hoc interpreters for difficult conversations. Physicians with high-level Spanish proficiency almost uniformly reported using their own Spanish skills. The majority (82%) of nurses had low-level Spanish proficiency, and frequently worked with professional interpreters for educating patients, but more often used ad hoc interpreters and their own Spanish skills for information-based scenarios, including medication administration. Physicians and nurses with limited Spanish proficiency use these skills, even in important clinical circumstances in the hospital. Health-care organizations should evaluate clinicians’ non-English language proficiency and set policies about use of language skills in clinical care.ABSTRACTBACKGROUNDLanguage barriers present a substantial communication challenge in the hospital setting.OBJECTIVETo describe how clinicians with various levels of Spanish language proficiency work with interpreters or their own Spanish skills in common clinical scenarios.DESIGN & PARTICIPANTSSurvey of physicians and nurses who report ever speaking Spanish with patients on a general medicine hospital floor.MEASUREMENTSSpanish proficiency rated on a 5-point scale, self-reported use of specific strategies (own Spanish skills, professional or ad-hoc interpreters) to overcome the language barrier.RESULTSSixty-eight physicians and 65 nurses participated. Physicians with low-level Spanish proficiency reported frequent use of ad-hoc interpreters for all information-based scenarios, except pre-rounding in the morning when most reported using their own Spanish skills. For difficult conversations and procedural consent, most used professional interpreters. Comparatively, physicians with medium proficiency reported higher rates of using their own Spanish skills for information-based scenarios, lower rates of professional interpreter use, and little use of ad-hoc interpreters. They rarely used their own Spanish skills or ad-hoc interpreters for difficult conversations. Physicians with high-level Spanish proficiency almost uniformly reported using their own Spanish skills. The majority (82%) of nurses had low-level Spanish proficiency, and frequently worked with professional interpreters for educating patients, but more often used ad hoc interpreters and their own Spanish skills for information-based scenarios, including medication administration.CONCLUSIONSPhysicians and nurses with limited Spanish proficiency use these skills, even in important clinical circumstances in the hospital. Health-care organizations should evaluate clinicians’ non-English language proficiency and set policies about use of language skills in clinical care.

Pauci-immune glomerulonephritis in individuals with disease associated with levamisole-adulterated cocaine: a series of 4 cases.

AbstractExposure to levamisole-adulterated cocaine can induce a distinct clinical syndrome characterized by retiform purpura and/or agranulocytosis accompanied by an unusual constellation of serologic abnormalities including antiphospholipid antibodies, lupus anticoagulants, and very high titers of antineutrophil cytoplasmic antibodies. Two recent case reports suggest that levamisole-adulterated cocaine may also lead to renal disease in the form of pauci-immune glomerulonephritis. To explore this possibility, we reviewed cases of pauci-immune glomerulonephritis between 2010 and 2012 at an inner city safety net hospital where the prevalence of levamisole in the cocaine supply is known to be high. We identified 3 female patients and 1 male patient who had biopsy-proven pauci-immune glomerulonephritis, used cocaine, and had serologic abnormalities characteristic of levamisole-induced autoimmunity. Each also had some other form of clinical disease known to be associated with levamisole, either neutropenia or cutaneous manifestations. One patient had diffuse alveolar hemorrhage. Three of the 4 patients were treated with short courses of prednisone and cyclophosphamide, 2 of whom experienced stable long-term improvement in their renal function despite ongoing cocaine use. The remaining 2 patients developed end-stage renal disease and became dialysis-dependent. This report supports emerging concern of more wide spread organ toxicity associated with the use of levamisole-adulterated cocaine.

Facilitators and barriers to implementing electronic referral and/or consultation systems: a qualitative study of 16 health organizations

BackgroundAccess to specialty care remains a challenge for primary care providers and patients. Implementation of electronic referral and/or consultation (eCR) systems provides an opportunity for innovations in the delivery of specialty care. We conducted key informant interviews to identify drivers, facilitators, barriers and evaluation metrics of diverse eCR systems to inform widespread implementation of this model of specialty care delivery.MethodsInterviews were conducted with leaders of 16 diverse health care delivery organizations between January 2013 and April 2014. A limited snowball sampling approach was used for recruitment. Content analysis was used to examine key informant interview transcripts.ResultsElectronic referral systems, which provide referral management and triage by specialists, were developed to enhance tracking and operational efficiency. Electronic consultation systems, which encourage bi-directional communication between primary care and specialist providers facilitating longitudinal virtual co-management, were developed to improve access to specialty expertise. Integrated eCR systems leverage both functionalities to enhance the delivery of coordinated, specialty care at the population level. Elements of successful eCR system implementation included executive and clinician leadership, established funding models for specialist clinician reimbursement, and a commitment to optimizing clinician workflows.ConclusionseCR systems have great potential to streamline access to and enhance the coordination of specialty care delivery. While different eCR models help solve different organizational challenges, all require institutional investments for successful implementation, such as funding for program management, leadership and clinician incentives.

Healthy behaviors, risk factor control and awareness of chronic kidney disease

Background/Aims: The association between chronic kidney disease (CKD) awareness and healthy behaviors is unknown. We examined whether CKD self-recognition is associated with healthy behaviors and achieving risk-reduction targets known to decrease risk of cardiovascular morbidity and CKD progression. Methods: CKD awareness, defined as a ‘yes’ response to ‘Has a doctor or other health professional ever told you that you had kidney disease?’, was examined among adults with CKD (eGFR <60 ml/min/1.73 m2) who participated in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Odds of participation in healthy behaviors (tobacco avoidance, avoidance of regular nonsteroidal anti-inflammatory drug use, and physical activity) and achievement of risk-reduction targets (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, systolic blood pressure control and glycemic control among those with diabetes) among those aware versus unaware of their CKD were determined by logistic regression, controlling for sociodemographics, access to care and comorbid conditions. Systolic blood pressure control was defined as <130 mm Hg (primary definition) or <140 mm Hg (secondary definition). Results: Of 2,615 participants, only 6% (n = 166) were aware of having CKD. Those who were aware had 82% higher odds of tobacco avoidance compared to those unaware (adjusted OR = 1.82, 95% CI 1.02–3.24). CKD awareness was not associated with other healthy behaviors or achievement of risk-reduction targets. Conclusions: Awareness of CKD was only associated with participation in one healthy behavior and was not associated with achievement of risk-reduction targets. To encourage adoption of healthy behaviors, a better understanding of barriers to participation in CKD-healthy behaviors is needed.

Pragmatic Clinical Trials in CKD: Opportunities and Challenges

Randomized controlled trials in CKD lag in number behind those of other chronic diseases, despite the high morbidity and mortality experienced by patients with kidney disease and the exorbitant costs of their health care. Observational studies of CKD frequently yield seemingly paradoxic associations of traditional risk factors with outcomes, making it difficult to extrapolate the results of trials conducted in people with normal kidney function to patients with CKD. However, many completed trials in CKD have been limited by intermediate outcomes of unclear clinical significance or narrow eligibility criteria that limit external validity, and implementation of proven therapies remains a challenge. It is therefore imperative that the nephrology community capitalize on recent interest in novel approaches to trial design, such as pragmatic clinical trials. These trials are meant to promote research within real world settings to yield clinically relevant results with greater applicability than those of traditional trials, while maintaining many advantages, such as controlling for potential sources of bias. We provide a description of pragmatic clinical trials and a discussion of advantages, disadvantages, and practical challenges inherent to this study design, in the context of specific scientific questions relevant to patients with CKD.

Chronic kidney disease and use of dental services in a united states public healthcare system: a retrospective cohort study

BackgroundAs several studies have shown an association between periodontal disease and chronic kidney disease (CKD), regular dental care may be an important strategy for reducing the burden of CKD. Access to dental care may be limited in the US public health system.MethodsIn this retrospective cohort study of 6,498 adult patients with (n = 2,235) and without (n = 4,263) CKD and at least 12 months of follow-up within the San Francisco Department of Public Health Community Health Network clinical databases, we examined the likelihood of having a dental visit within the observation period (2005-2010) using Cox proportional hazards models. To determine whether dental visits reflected a uniform approach to preventive service use in this setting, we similarly examined the likelihood of having an eye visit among those with diabetes, for whom regular retinopathy screening is recommended. We defined CKD status by average estimated glomerular filtration rate based on two or more creatinine measurements ≥ 3 months apart (no CKD, ≥ 60 ml/min/1.73 m2; CKD, < 60 ml/min/1.73 m2).ResultsOnly 11.0% and 17.4% of patients with and without CKD, respectively, had at least one dental visit. Those with CKD had a 25% lower likelihood of having a dental visit [HR = 0.75, 95% CI (0.64-0.88)] than those without CKD after adjustment for confounders. Among the subgroup of patients with diabetes, 11.8% vs. 17.2% of those with and without CKD had a dental visit, while 58.8% vs. 57.8% had an eye visit.ConclusionsDental visits, but not eye visits, in a US public healthcare setting are extremely low, particularly among patients with CKD. Given the emerging association between oral health and CKD, addressing factors that impede dental access may be important for reducing the disparate burden of CKD in this population.

Is Awareness of Chronic Kidney Disease Associated with Evidence-Based Guideline-Concordant Outcomes?

Background: Awareness of chronic kidney disease (CKD) is low. Efforts are underway to increase recognition of CKD among patients, assuming that such an increase will lead to better outcomes through greater adherence to proven therapies. Few studies have tested this assumption. Methods: CKD awareness, defined by a ‘yes’ answer to ‘Have you ever been told by a healthcare provider you have weak or failing kidneys?’, was assessed among 2,404 adults with CKD stages 1–4, who participated in the 2003–2008 National Health and Nutrition Examination Surveys. Odds of blood pressure (BP) control, self-reported use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), and glycemic control, were determined among those aware vs. unaware of their CKD. Results: Optimal BP control, ACEI/ARB use and glycemic control were low in the US adult population with CKD, although there was a recent increase in attainment of guideline-concordant BP control. Odds of BP control and ACEI/ARB use were not different among individuals aware of their CKD compared to those unaware (adjusted odds ratio (AOR) 0.91; 95% CI 0.52–1.58 and AOR 0.75; 0.44–1.30, respectively). CKD awareness among diabetic participants was not associated with glycemic control (AOR 0.41; 95% CI 0.14–1.18). Conclusion: Awareness of CKD is not associated with more optimal BP control, ACEI/ARB use or glycemic control. Future efforts in this area should further explore the measurement of CKD awareness and behaviors associated with CKD awareness.

Leveraging an electronic referral system to build a medical neighborhood.

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.