Matthew B. Allen

Clinical Trial: Comparative Effectiveness of Cephalexin Plus Trimethoprim-Sulfamethoxazole Versus Cephalexin Alone for Treatment of Uncomplicated Cellulitis: A Randomized Controlled Trial

BACKGROUND Community-associated methicillin-resistant S. aureus (CA-MRSA) is the most common organism isolated from purulent skin infections. Antibiotics are usually not beneficial for skin abscess, and national guidelines do not recommend CA-MRSA coverage for cellulitis, except purulent cellulitis, which is uncommon. Despite this, antibiotics targeting CA-MRSA are prescribed commonly and increasingly for skin infections, perhaps due, in part, to lack of experimental evidence among cellulitis patients. We test the hypothesis that antibiotics targeting CA-MRSA are beneficial in the treatment of cellulitis. METHODS We performed a randomized, multicenter, double-blind, placebo-controlled trial from 2007 to 2011. We enrolled patients with cellulitis, no abscesses, symptoms for <1 week, and no diabetes, immunosuppression, peripheral vascular disease, or hospitalization (clinicaltrials.gov NCT00676130). All participants received cephalexin. Additionally, each was randomized to trimethoprim-sulfamethoxazole or placebo. We provided 14 days of antibiotics and instructed participants to continue therapy for ≥1 week, then stop 3 days after they felt the infection to be cured. Our main outcome measure was the risk difference for treatment success, determined in person at 2 weeks, with telephone and medical record confirmation at 1 month. RESULTS We enrolled 153 participants, and 146 had outcome data for intent-to-treat analysis. Median age was 29, range 3-74. Of intervention participants, 62/73 (85%) were cured versus 60/73 controls (82%), a risk difference of 2.7% (95% confidence interval, -9.3% to 15%; P = .66). No covariates predicted treatment response, including nasal MRSA colonization and purulence at enrollment. CONCLUSIONS Among patients diagnosed with cellulitis without abscess, the addition of trimethoprim-sulfamethoxazole to cephalexin did not improve outcomes overall or by subgroup. CLINICAL TRIALS REGISTRATION NCT00676130.

What are the harms of refusing to allow living kidney donation? An expanded view of risks and benefits.

Recent Organ Procurement and Transplantation Network policies relating to living kidney donation (LKD) warrant renewed attention to the ethics of transplantation from living donors. These policies focus on risks related to potential donor evaluation, informed consent and follow‐up. The ethical basis of living donation is a favorable risk/benefit ratio for the donor, but regulations and research have given less attention to the benefits of donation. Relatedly, the transplant field has also failed to consider potential harms from denying patients the opportunity to donate. These harms may be substantial in the setting of directed kidney donation to a spouse/partner, sibling or child. We argue that complete assessment of donor risks and benefits demands consideration of not only the risks and benefits of donation, but also those of refusing a donor. In contrast to the ever‐expanding literature on risks of donation, there are no data describing outcomes for individuals who were turned down as kidney donors. We consider factors contributing to this omission in the transplant literature, argue that current regulations may perpetuate a narrow understanding of relevant risks and benefits in LKD, and identify areas for improvement in research and clinical practice.

Preferences for Resuscitation and Intubation Among Patients With Do-Not-Resuscitate/Do-Not-Intubate Orders

OBJECTIVE To determine the accuracy of do-not-resuscitate/do-not-intubate (DNR/DNI) orders in representing patient preferences regarding cardiopulmonary resuscitation (CPR) and intubation. PATIENTS AND METHODS We conducted a prospective survey study of patients with documented DNR/DNI code status at an urban academic tertiary care center that serves approximately 250,000 patients per year. From October 1, 2010, to October 1, 2011, research staff enrolled a convenience sample of patients from the inpatient medical service, providing them with a series of emergency scenarios for which they related their treatment preference. We used the Kendall τ rank correlation coefficient to examine correlation between degree of illness reversibility and willingness to be resuscitated. Using bivariate statistical analysis and multivariate logistic regression analysis, we examined predictors of discrepancies between code status and patient preferences. Our main outcome measure was the percentage of patients with DNR/DNI orders wanting CPR and/or intubation in each scenario. We hypothesized that patients with DNR/DNI orders would frequently want CPR and/or intubation. RESULTS We enrolled 100 patients (mean ± SD age, 78 ± 13.7 years). A total of 58% (95% CI, 48%-67%) wanted intubation for angioedema, 28% (95% CI, 20%-3.07%) wanted intubation for severe pneumonia, and 20% (95% CI, 13%-29%) wanted a trial resuscitation for cardiac arrest. The desire for intubation decreased as potential reversibility of the acute disease process decreased (Kendall τ correlation coefficient, 0.45; P<.0002). CONCLUSION Most patients with DNR/DNI orders want CPR and/or intubation in hypothetical clinical scenarios, directly conflicting with their documented DNR/DNI status. Further research is needed to better understand the discrepancy and limitations of DNR/DNI orders.

Donor Hemodynamics as a Predictor of Outcomes After Kidney Transplantation From Donors After Cardiac Death

Donation after cardiac death is an important source of transplantable organs, but evidence suggests donor warm ischemia contributes to inferior outcomes. Attempts to predict recipient outcome using donor hemodynamic measurements have not yielded statistically significant results. We evaluated novel measures of donor hemodynamics as predictors of delayed graft function and graft failure in a cohort of 1050 kidneys from 566 donors. Hemodynamics were described using regression line slopes, areas under the curve, and time beyond thresholds for systolic blood pressure, oxygen saturation, and shock index (heart rate divided by systolic blood pressure). A logistic generalized estimation equation model showed that area under the curve for systolic blood pressure was predictive of delayed graft function (above median: odds ratio 1.42, 95% confidence interval [CI] 1.06–1.90). Multivariable Cox regression demonstrated that slope of oxygen saturation during the first 10 minutes after extubation was associated with graft failure (below median: hazard ratio 1.30, 95% CI 1.03–1.64), with 5‐year graft survival of 70.0% (95%CI 64.5%–74.8%) for donors above the median versus 61.4% (95%CI 55.5%–66.7%) for those below the median. Among older donors, increased shock index slope was associated with increased hazard of graft failure. Validation of these findings is necessary to determine the utility of characterizing donor warm ischemia to predict recipient outcome.

The Ethics of Promoting Living Kidney Donation Using Nonargumentative Influence: Applications, Concerns, and Future Directions

Recommendations from the 2014 Consensus Conference on Best Practices in Living Kidney Donation reflect increasing attention to overcoming barriers to donation as a means of expanding access to living donor kidney transplantation. “High priority” initiatives include empowering transplant candidates and their loved ones in their search for a living kidney donor. Transplant programs are assuming an unprecedented role as facilitators of patients’ solicitation for donors, and nonprofits are promoting living kidney donation (LKD) in the community. New strategies to promote LKD incorporate “nonargumentative” forms of influence (i.e. approaches to shaping behavior that do not attempt to persuade through reason) such as appeals to emotion, messenger effects and social norms. These approaches have raised ethical concerns in other settings but have received little attention in the transplantation literature despite their increasing relevance. Previous work on using nonargumentative influence to shape patient behavior has highlighted implications for (1) the relationship between influencer and influenced and (2) patient autonomy. We argue that using nonargumentative influence to promote LKD is a promising strategy that can be compatible with ethical standards. We also outline potential concerns and solutions to be implemented in practice.

Transforming Living Kidney Donation with a Comprehensive Strategy.

Matthew Allen and Peter Reese argue that evidence-based efforts should be implemented to expand living kidney donation.

The Time Burden of Alcohol-Based Hand Cleanser When Using Nonsterile Gloves

We quantified the time burden of alcohol-based handrub accompanying nonsterile-glove use among emergency physicians, through observation in controlled and clinical settings. We report gloving episodes per hour, gloving times with and without handrub, and handrub recommendations compliance. Handrub adds 46 seconds to each glove-use episode, and we provide national extrapolations.

Financial Incentives for Living Kidney Donation: Ethics and Evidence

The widening gap between the number of donated kidneys and the need for kidney transplants has driven interest in incentivizing living kidney donation. Proposals to increase living kidney donation rates using financial incentives have generated vigorous ethical critiques, which can be placed into

Outcomes for individuals turned down for living kidney donation: XXXX

A better understanding of the consequences of being turned down for living kidney donation could help transplant professionals to counsel individuals considering donation.

The Language of Goals of Care: Framing Preferences at the End of Life

Correspondence Affi liations: From the Department of Medicine (Dr Wahidi) and the Department of Pharmacy (Dr Barbour), Duke University Medical Center; and the Medical University of South Carolina (Dr Silvestri). Financial/nonfi nancial disclosures: The authors have reported to CHEST the following confl icts of interest: Dr Wahidi was an investigator on the multicenter trial of Fospropofol. Dr Silvestri was an investigator on the multicenter trial of Fospropofol; he was a recipient of grant funding from Olympus America and MGI Pharma for a project assessing fospropofol for bronchoscopy and from Allegro Diagnostics Corp for assessing malignancy in patients with abnormal chest radiographs. Dr Barbour has reported to CHEST that no potential confl icts of interest exist with any companies/organizations whose products or services may be discussed in this article . Correspondence to: Momen M. Wahidi, MD, MBA, FCCP, Department of Internal Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Box 3683, Durham, NC 27710; e-mail: momen.wahidi@ duke.edu