Generational differences in practice site selection criteria amongst primary care physicians.

Background and Objectives: Generational differences are often viewed as shaping the overall attitudes and actions of different age cohorts. It is essential to understand the motivations and generational differences in primary care physicians for efforts to recruit, retain, and educate the future physician workforce. Determining what factors most influence different generations of primary care physicians when choosing a practice site is essential to build our future primary care system. This study examined generational differences in the factors that attracted primary care physicians to their current practice. Methods: A survey instrument was mailed to all active members of the North Carolina Medical Board who listed their primary occupation as a primary care specialty. The survey consisted of 24 demographic questions regarding personal and practice variables and a list of 21 reasons for choosing a practice location measured on a 7-point Likert type scale. A total of 975 surveys were returned and usable for the final analysis, for a return rate of 34.5%. Data were analyzed using regression and correlation procedures to determine attitudes of each generation and factors that significantly influenced responses. Results: While slight differences between generations did exist, the overall choices for choosing a site remained stable across generations. Personality of the practice, on-call responsibilities, ability to practice comprehensive care, and location were deemed the most important factors for all generations. Differences between various demographic groups and Family Medicine versus other primary care specialties were minor with very little alteration of the top ten items being seen between groups. Conclusion: This study indicated that there were few differences between generations regarding primary reasons for choosing a practice site. In addition, factors remained remarkably similar across different specialties, family situations, genders, and ethnic groups. Several of the top reasons that primary care physicians indicate are the most important for site selection were also potentially modifiable, such as on-call responsibilities, practice personality, and ability to practice comprehensive care. Managers, clinicians, and educators can potentially utilize this information to better prepare and recruit current and future generations of primary care physicians.ECU Open Access Publishing Fun

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background: Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world. Methods and Findings: 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72–1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54–0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39–0.64 for women; HR 0.79, CI 0.62–1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12–2.04; p = 0.007). Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen

Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.

BackgroundAntiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and findings1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p&lt;0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).ConclusionEFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial registrationwww.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary

Primary and secondary time-to-event outcomes for comparison of efavirenz plus emtricitabine-tenofovir-DF to efavirenz plus lamivudine-zidovudine using data collected through 31-May-2010.

a<p>Also known as relative risk. Estimated from Cox regression model stratified by both country and RNA stratum and including randomized treatment group as sole covariate.</p>b<p><i>p</i>-Value calculated from stratified log-rank test between arms. Not applicable (NA) because no formal hypothesis testing was performed based on DSMB recommendations.</p>c<p>The five most common causes of death were infection (17 deaths) and unknown cause (five deaths) followed by suicide, trauma, and stroke (three deaths each).</p>d<p>Disease progression diagnoses are in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001290#pmed.1001290.s012" target="_blank">Table S7</a>; grade 3 and 4 laboratory adverse events in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001290#pmed.1001290.s013" target="_blank">Table S8</a>; and signs and symptoms in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001290#pmed.1001290.s014" target="_blank">Table S9</a>.</p>e<p>All events meeting these criteria are reported; some participants met criteria for multiple endpoints.</p>f<p>Confirmed plasma HIV RNA≥1,000 copies/ml at study week 16 or later.</p>g<p>Change in any component of initial randomized antiretroviral regimen.</p>h<p>The following antiretroviral substitutions were prespecified and were not included in this endpoint: stavudine or TDF for ZDV, nevirapine for EFV, or didansoine for TDF.</p>i<p>CD4+ lymphocytes <100/µl at week 48 or later.</p

Primary and secondary time-to-event outcomes for the comparison of atazanavir plus didanosine-EC and emtricitabine to efavirenz plus lamivudine-zidovudine using data collected through 22 May 2008.

a<p>Also known as relative risk. Estimated from Cox regression model stratified by both country and RNA stratum and including randomized treatment group as sole covariate.</p>b<p><i>p</i>-Value calculated from stratified log-rank test between arms.</p>c<p>The five most common causes of death were infection (six deaths), liver disease (three deaths), malignancy (two deaths), suicide (two deaths), and unknown cause (two deaths).</p>d<p>Disease progression diagnoses are in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001290#pmed.1001290.s007" target="_blank">Table S2</a>; grade 3 and 4 laboratory events in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001290#pmed.1001290.s008" target="_blank">Table S3</a>; and signs and symptoms in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001290#pmed.1001290.s009" target="_blank">Table S4</a>.</p>e<p>All events meeting these criteria are reported; some participants met criteria for multiple endpoints.</p>f<p>Confirmed plasma HIV RNA≥1,000 copies/ml at study week 16 or later.</p>g<p>Elevated bilirubin concentration not included.</p>h<p>Change in any component of initial randomized antiretroviral regimen.</p>i<p>The following antiretroviral substitutions were prespecified and were not included in this endpoint: TDF for DDI, stavudine or TDF for ZDV, or nevirapine for EFV.</p>j<p>CD4+ lymphocytes <100/µl at week 48 or later.</p

Subgroup analysis for primary efficacy and safety endpoints by randomly assigned antiretroviral treatment.

<p>Subgroup analyses were conducted for the baseline covariates self-reported sex and race/ethnicity and the countries in which the participating research sites were located. The relative risk and 95% CIs are provided for all participants (overall) and for each subgroup. <i>p</i>-Value represents interaction test between baseline covariate and randomized treatment group. Comparisons between ATV plus DDI and FTC and EFV plus 3TC-ZDV are in red. Comparisons between EFV plus FTC-TDF and EFV plus 3TC-ZDV are in green. (A) Treatment failure (efficacy) composite endpoint. (B) Safety events composite endpoint.</p

Efficacy and safety of randomized study treatment over time.

<p>(A–H) black circles, EFV plus 3TC-ZDV; red triangles, ATV plus DDI-EC and FTC; green squares, EFV plus FTC-TDF. (A–B) Estimated cumulative probability of antiretroviral regimen failure defined by the protocol-specified primary efficacy endpoint: comparison of EFV plus 3TC-ZDV to ATV plus FTC and DDI (A) and EFV plus FTC-TDF (B). (C–D) Proportion of participants with plasma HIV-1 RNA less than 400 copies/ml for comparison of EFV plus 3TC-ZDV to ATV plus FTC and DDI (C) and EFV plus FTC-TDF (D). These comparisons included all randomized study participants according to assigned study treatment. The analysis that counted missing values as greater than 400 copies/ml (open symbols) is truncated at the maximum potential duration of study follow-up for participants who entered the study at the end of the enrollment period (144 wk). (E–F) Median change in CD4+ lymphocyte count from screening value over time for comparison of EFV plus 3TC-ZDV to ATV plus FTC and DDI (E) and EFV plus FTC-TDF (F). (G–H) Estimated cumulative probability a safety endpoint over time for comparison of EFV plus 3TC-ZDV to ATV plus FTC and DDI (G) and EFV plus FTC-TDF (H). For (A–D, G and H), bars represent the 95% CI for the estimate. For (E–F), bars represent the interquartile range. (A–H) The number of evaluable participants at each time point is provided for each randomized treatment assignment.</p