Understanding the experience of care managers and relationship with patient outcomes: the COMPASS initiative.

OBJECTIVE: To understand how care managers implemented COMPASS and if this was related to patient health outcomes. METHODS: A total of 96 COMPASS care managers were approached to participate in the online survey and 93 (97%) provided responses. Correlations were generated between key survey responses and the average number of care management contacts, patient depression, blood pressure and glycosylated hemoglobin outcomes. RESULTS: Patients of care managers who reported spending more time on COMPASS-related tasks had higher rates of depression improvement (r=0.34; P=.002) and remission (r=0.27; P=.02) as well as higher rates of blood pressure control (r=0.29; P=.03). CONCLUSIONS: To improve the effectiveness of care management in collaborative care models, particularly for patients with comorbid conditions and complex nonmedical needs, care managers need the support of social work and administrative support staff. Care managers for this patient population would also benefit from more intensive training in nonpharmacological depression treatment, such as motivational interviewing and behavioral activation. Additionally, systems support is needed such as education for primary care teams and psychiatry on the value of collaborative care models and integration of population management tools into electronic medical records.

Inhibitors of multiple mutants of Plasmodium falciparum dihydrofolate reductase and their antimalarial activities.

Novel analogues of pyrimethamine (Pyr) and cycloguanil (Cyc) have been synthesized and tested as inhibitors of Plasmodium falciparum dihydrofolate reductase carrying triple (N51I+C59R+S108N, C59R+S108N+I164L) and quadruple (N51I+C59R+S108N+I164L) mutations responsible for antifolate resistance. The inhibitors were designed to avoid steric clash of the p-Cl group of the inhibitors with the side chain of Asn108, augmented by additional mutations of the resistant mutants. Cycloguanil derivatives were also designed to avoid steric clash with the side chain of Val16 in the A16V+S108T mutant. Many compounds have inhibition constants (K(i)) at the low nanomolar level against the mutant enzymes and a number have good antimalarial activities against resistant P. falciparum parasites bearing multiple mutations in the S108N series and A16V+S108T mutant enzymes. These compounds in the Pyr and Cyc series exhibit low and moderate cytotoxicity to nontumor (Vero) and tumor (KB, BC) cell lines. Some of these inhibitors are therefore potential candidates for further development as antimalarials.