Practice-site-level measures of primary care comprehensiveness and their associations with patient outcomes.

OBJECTIVES: To develop two practice-site-level measures of comprehensiveness and examine their associations with patient outcomes, and how their performance differs from physician-level measures. DATA SOURCES: Medicare fee-for-service claims. STUDY DESIGN: We calculated practice-site-level comprehensiveness measures (new problem management and involvement in patient conditions) across 5286 primary care physicians (PCPs) at 1339 practices in the Comprehensive Primary Care initiative evaluation in 2013. We assessed their associations with practices' attributed beneficiaries' 2014 total Medicare expenditures, hospitalization rates, ED visit rates. We also examined variation in PCPs' comprehensiveness across PCPs within practices versus between primary care practices. Finally, we compared associations of practice-site and PCP-level measures with outcomes. PRINCIPAL FINDINGS: The measures had good variation across primary care practices, strong validity, and high reliability. Receiving primary care from a practice at the 75th versus 25th percentile on the involvement in patient conditions measure was associated with $21.93 (2.8%) lower total Medicare expenditures per beneficiary per month (P < .01). Receiving primary care from a practice at the 75th versus 25th percentile on the new problem management measure was associated with $14.77 (1.9%) lower total Medicare expenditures per beneficiary per month (P < .05); 8.84 (3.0%) fewer hospitalizations (P < .001), and 21.27 (3.1%) fewer ED visits per thousand beneficiaries per year (P < .01). PCP comprehensiveness varied more within than between practices. CONCLUSIONS: More comprehensive primary care practices had lower Medicare FFS expenditures, hospitalization, and ED visit rates. Both PCP and practice-site level comprehensiveness measures had strong construct and predictive validity; PCP-level measures were more precise.

New approaches to measuring the comprehensiveness of primary care physicians.

OBJECTIVE: To develop claims-based measures of comprehensiveness of primary care physicians (PCPs) and summarize their associations with health care utilization and cost. DATA SOURCES AND STUDY SETTING: A total of 5359 PCPs caring for over 1 million Medicare fee-for-service beneficiaries from 1404 practices. STUDY DESIGN: We developed Medicare claims-based measures of physician comprehensiveness (involvement in patient conditions and new problem management) and used a previously developed range of services measure. We analyzed the association of PCPs' comprehensiveness in 2013 with their beneficiaries' emergency department, hospitalizations rates, and ambulatory care-sensitive condition (ACSC) admissions (each per 1000 beneficiaries per year), and Medicare expenditures (per beneficiary per month) in 2014, adjusting for beneficiary, physician, practice, and market characteristics, and clustering. PRINCIPAL FINDINGS: Each measure varied across PCPs and had low correlation with the other measures-as intended, they capture different aspects of comprehensiveness. For patients whose PCPs' comprehensiveness score was at the 75th vs 25th percentile (more vs less comprehensive), patients had lower service use (P < 0.05) in one or more measures: involvement with patient conditions: total Medicare expenditures, -$17.4 (-2.2 percent); hospitalizations, -5.5 (-1.9 percent); emergency department (ED) visits, -16.3 (-2.4 percent); new problem management: total Medicare expenditures, -$13.3 (-1.7 percent); hospitalizations, -7.0 (-2.4 percent); ED visits, -19.7 (-2.9 percent); range of services: ED visits, -17.1 (-2.5 percent). There were no significant associations between the comprehensiveness measures and ACSC admission rates. CONCLUSIONS: These measures demonstrate strong content and predictive validity and reliability. Medicare beneficiaries of PCPs providing more comprehensive care had lower hospitalization rates, ED visits, and total Medicare expenditures.

Interactions of the C-11 hydroxyl of tetrodotoxin with the sodium channel outer vestibule.

The highly selective sodium channel blocker, tetrodotoxin (TTX) has been instrumental in characterization of voltage-gated sodium channels. TTX occludes the ion-permeation pathway at the outer vestibule of the channel. In addition to a critical guanidinium group, TTX possesses six hydroxyl groups, which appear to be important for toxin block. The nature of their interactions with the outer vestibule remains debatable, however. The C-11 hydroxyl (C-11 OH) has been proposed to interact with the channel through a hydrogen bond to a carboxyl group, possibly from domain IV. On the other hand, previous experiments suggest that TTX interacts most strongly with pore loops of domains I and II. Energetic localization of the C-11 OH was undertaken by thermodynamic mutant cycle analysis assessing the dependence of the effects of mutations of the adult rat skeletal muscle Na(+) channel (rNa(v)1.4) and the presence of C-11 OH on toxin IC(50). Xenopus oocytes were injected with the mutant or native Na(+) channel mRNA, and currents were measured by two-electrode voltage clamp. Toxin blocking efficacy was determined by recording the reduction in current upon toxin exposure. Mutant cycle analysis revealed that the maximum interaction of the C-11 OH was with domain IV residue D1532 (DeltaDeltaG: 1.0 kcal/mol). Furthermore, C-11 OH had significantly less interaction with several domain I, II, and III residues. The pattern of interactions suggested that C-11 was closest to domain IV, probably involved in a hydrogen bond with the domain IV carboxyl group. Incorporating this data, a new molecular model of TTX binding is proposed.

Energetic localization of saxitoxin in its channel binding site.

Saxitoxin (STX) selectively blocks the voltage-gated sodium channel at the outer vestibule lined by P-loops of the four domains. Neosaxitoxin has an additional -OH group at the N1 position of the 1,2,3 guanidinium (N1-OH) that interacts with domains I and IV of the Na(+) channel. Determination of a second toxin interaction with the channel would fix the location of STX. Gonyautoxin 2,3 and Gonyautoxin 1,4 are C-11 sulfated derivatives of saxitoxin and neosaxitoxin, respectively. We used these variants to constrain the STX docking orientation by energetically localizing the C-11 sulfate in the outer vestibule. Interactions between the C-11 sulfate and each of the four domains of the channel were determined by a systematic approach to mutant cycle analysis in which all known carboxyl groups important for site 1 toxin binding were neutralized, allowing energetic triangulation of the toxin sulfate and overcoming some limitations of mutant cycles. Toxin IC(50)s were measured by two-electrode voltage clamp from Xenopus oocytes injected with the channel mRNA. Three unique types of analysis based on the coupling results localized the C-11 sulfate between domains III and IV. Combined with our previous report, the data establish the orientation of STX in the outer vestibule and confirm the clockwise arrangement of the channel domains.