Bonnie C. Greenwood

Importance: Rheumatic heart disease (RHD) in the developing world results in critical disability among children, adolescents, and young adults—marginalizing a key population at its peak age of productivity. Few regions in sub‐Saharan Africa have independently created an effective strategy to detect and treat streptococcal infection and mitigate its progression to RHD.Objective: We describe a unique collaboration, where the Rwanda Ministry of Health, the Rwanda Heart Foundation, and an expatriate humanitarian cardiac surgery program have together leveraged an innovative partnership as a means to expand Rwanda’s current capacity to address screening and primary prevention, as well as provide life‐saving cardiac surgery for patients with critical RHD.Evidence review: Interviews with key personnel and review of administrative records were conducted to obtain qualitative and quantitative data on the recruitment of clinical personnel, procurement of equipment, and program finances. The number of surgical cases completed and the resultant clinical outcomes are reviewed.Findings: From 2008 to 2013, six annual visits were completed. A total of 128 prosthetic valves have been implanted in 86 complex patients in New York Heart Association (NYHA) class III or IV heart failure, with excellent clinical outcomes (5 % 30‐day mortality). Postoperative complications included a cerebrovascular accident (n = 1) and hemorrhage, requiring reoperation (n = 2). All procedures were performed with participation of local personnel.Conclusions and relevance: This strategy provides a reliable and consistent model of sophisticated specialty care delivery; inclusive of patient‐centered cardiac surgery, mentorship, didactics, skill transfer, and investment in a sustainable cardiac program to address critical RHD in sub‐Saharan Africa.

Utilization of high-dose extended-interval aminoglycoside therapy (HEAT) in patients with cystic fibrosis (CF) is supported by primary literature and national guidelines. We sought to evaluate the effectiveness of a local aminoglycoside guideline to achieve pharmacodynamic goals in patients with CF that received ≧3 doses of HEAT from 2005 to 2011. Patients with renal dysfunction at baseline, status-post-lung transplant, or receiving inhaled tobramycin were excluded. In the 282 patient admissions, the average initial tobramycin dose was 10·3 mg/kg with an average initial peak of 21·5 mg/l. At least one dose titration was seen in 39% of patients. Patients who achieved the pharmacodynamic goal received a higher dose (10·4 mg/kg versus 9·7 mg/kg; P<0·001). A mean starting dose of tobramycin at 10·3 mg/kg every 24 hours achieved an average peak above goal. Higher initial dosing resulted in a higher likelihood of achieving the pharmacodynamic goal.

We thank Dr. Cook and colleagues for their insightful letter regarding our recent review. Their comments echo many of the discussion points of our review relating to clinical pharmacology and a global lack of quality evidence surrounding pharmacotherapy for posttraumatic seizure (PTS) prophylaxis. We agree with the recommendations in the guidelines of both the Brain Trauma Foundation¹ and the American Academy of Neurology.² Concerns appear to lie with our interpretation and discussion of the secondary agents levetiracetam, carbamazepine, and valproate.

Peer reviewed article authored by (Rocchio MA, Belisle CD, Greenwood BC, Cotugno MC, Szumita PM). Read article or submit your manuscript for publishing.

Purpose: Early clinical trials of recombinant human activated protein C (rhAPC) for severe sepsis excluded patients at high risk of bleeding. Recent literature suggests bleeding rates are higher in clinical practice and may be associated with worsened outcomes. Our objective was to evaluate baseline demographics; incidence, and risk factors for major bleeding; and mortality of patients receiving rhAPC for severe sepsis at our institution. Methods: A retrospective study was performed for all patients receiving rhAPC for treatment of severe sepsis at a tertiary academic medical center from January 2002 to June 2009. Demographic information, clinical variables, intensive care unit, and hospital outcomes were recorded. Results: Of the 156 patients that received rhAPC, 54 (34.6%) did not meet institutional criteria for safe use at baseline due to bleeding precaution or contraindication. Twenty-three (14.7%) patients experienced a major bleeding event. Multivariate analysis demonstrated baseline International Normalized Ratio ≥2.5 (odds ratio [OR] 3.68, 95% confidence interval [CI]: 1.28–10.56; P = 0.03) and platelet count ≤100 × 10³/mm³ (OR 2.86, 95% CI: 1.07–7.67; P = 0.01) as significant predictors of a major bleed. Overall hospital mortality was 57.7%. Multivariate analysis demonstrated the presence of ≥3 organ dysfunctions (OR 2.46, 95% CI: 1.19–5.09; P < 0.05) and medical intensive care unit admission (OR 1.99, 95% CI: 1.00–3.98; P = 0.05) were independent variables associated with hospital mortality. Conclusion: Patients receiving rhAPC at our institution had higher APACHE II scores, mortality, and major bleeding events than published postmarketing studies. Risk factors for major bleeding other than package-labeling contraindications and bleeding precautions were identified in our patient population.

Purpose. Antiepileptics used for seizure prophylaxis after traumatic brain injury (TBI) are reviewed.Summary. Of the 275,000 people who are hospitaliz

Purpose: The purpose of this study was to evaluate the extended stability of extemporaneously prepared regular human insulin 100 units in 0.9% sodium chloride at a total volume of 100 mL under refrigeration. Methods: Three admixtures of regular human insulin were prepared aseptically under a laminar flow hood at time zero. They were prepared by withdrawing 1 mL of regular human insulin with a concentration of 100 units/mL and adding it to a sufficient quantity of 0.9% sodium chloride for injection in a Polyvinylchloride (PVC) bag to yield a total volume of 100 mL. The 3 admixtures were stored refrigerated(2°C to 8°C [36°F to 46°F]) and three 1 mL samples of each admixture were withdrawn, transferred to a test tube, and frozen(–30°C to −15°C [–22°F to 5°F]) at hours 0, 6, 12, 36, 48, 72, 96, 120, 144, and 168. Insulin concentrations were measured by chemiluminescent immunoassay. The time points were considered stable if the mean concentration of the samples exceeded 90% of the equilibrium concentration at hour 6. Results: The equilibrium concentration was 0.57 units/mL. Time points were considered stable if the mean concentration was at least 0.52 units/mL. All time points retained at least 90% of the equilibrium concentration with the exception of hour 120(0.46 ± 0.05 units/mL). At hour 168, the mean concentration was 0.63 ± 0.07 units/mL. Conclusion: Regular human insulin 100 units added to 0.9% sodium chloride for injection in a PVC bag to yield a total volume of 100 mL is stable for 168 hours when stored at 2°C to 8°C(36°F to 46°F).