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Introduction: The objectives of this study were to examine if self-reported access to primary care is associated with actual patient wait times and use of telephone visits, and to assess whether this relationship differs by rural residence. Methods: This study used 2016 administrative data from 994 primary care clinics within the Veterans Health Administration. Multiple-linear regression was used to examine relationships between patient perceptions of access and average actual patient wait time, use of telephone visits, and rural residence. Average panel size, clinic type, and panel severity were included as model covariates with cross-product terms for actual wait time, telephone use, and rurality to test for interactions. Results: This study found patient perceptions of access aggregated at the clinic level to be conditional on the relationship between use of telephone visits, actual patient wait times, and rural residence. As actual wait time for routine appointments increases, Veterans served by clinics with a higher percent of rural Veterans perceive telephone visits more positively. Discussion: These findings contribute to our understanding of factors associated with patient perceptions of access by highlighting complex interrelationships between strategies intended to improve access to care and how they can have differing impacts on perceptions among those living in rural or urban locations.

Key Points Question What are the incidence, risk factors, and outcomes associated with in-hospital acute myocardial infarction (AMI)? Findings This cohort study of 1.3 million patients hospitalized in US Veterans Health Administration facilities found an incidence of in-hospital AMI of 4.27 per 1000 admissions, and risk factors associated with in-hospital AMI included history of coronary artery disease, elevated heart rate, low hemoglobin level, and elevated white blood cell count. Compared with a matched control group, mortality was significantly higher for in-hospital AMI. Meaning In-hospital AMI is common and is associated with prior cardiovascular disease, physiological disturbances, and poor survival., This cohort study investigates the incidence, risk factors, and outcomes associated with in-hospital acute myocardial infarction (AMI) among a population of patients hospitalized in US Veterans Health Administration facilities., Importance Studies of acute myocardial infarction (AMI) occurring outside the hospital have informed approaches to addressing risk, treatment, and patient outcomes. Similar insights for in-hospital AMI are lacking. Objective To determine the incidence, risk factors, and outcomes associated with in-hospital AMI. Design, Setting, and Participants Cohort, nested case-control, and matched cohort study of patients hospitalized in US Veterans Health Administration facilities between July 2007 and September 2009. The incidence of in-hospital AMI was determined from a complete cohort of in-hospital AMI relative to the total number of inpatient admissions. From the in-hospital AMI cohort, detailed medical record review was performed on 687 cases and 687 individually matched controls. Risk factors and outcomes associated with in-hospital AMI were determined from matched comparison of in-hospital AMI cases to hospitalized controls. Exposures Candidate risk factors for in-hospital AMI included characteristics at the time of admission and in-hospital variables prior to the index date. Main Outcomes and Measures In the determination of the incidence and risk factors associated with in-hospital AMI, the outcome of interest was in-hospital AMI. All-cause mortality was the main outcome of interest following in-hospital AMI. Results A total of 5556 patients with in-hospital AMI (mean [SD] age, 73 [10] years; 5456 [98.2%] male) were identified among 1.3 million admissions, with an incidence of 4.27 in-hospital AMI events per 1000 admissions. Independent risk factors associated with in-hospital AMI included intensive care unit setting, history of coronary artery disease, heart rate greater than 100 beats/min, hemoglobin level less than 8 g/dL, and white blood cell count 14 000/μL or greater. Compared with the matched control group, mortality was significantly higher for patients with in-hospital AMI (in-hospital mortality, 26.4% vs 4.2%; 30-day mortality, 33.0% vs 10.0%; 1-year mortality, 59.2% vs 34.4%). Conclusions and Relevance In-hospital AMI was common and associated with common cardiovascular risk factors and markers of acute illness. Patient outcomes following in-hospital AMI were poor, with 1-year mortality approaching 60%. Further study of in-hospital AMI may yield opportunities to reduce in-hospital AMI risk and improve patient outcomes.

Defining the specificities of the anti-human immunodeficiency virus type 1 (HIV-1) envelope antibodies able to mediate broad heterologous neutralization will assist in identifying targets for an HIV-1 vaccine. We screened 70 plasmas from chronically HIV-1-infected individuals for neutralization breadth. Of these, 16 (23%) were found to neutralize 80% or more of the viruses tested. Anti-CD4 binding site (CD4bs) antibodies were found in almost all plasmas independent of their neutralization breadth, but they mainly mediated neutralization of the laboratory strain HxB2 with little effect on the primary virus, Du151. Adsorption with Du151 monomeric gp120 reduced neutralizing activity to some extent in most plasma samples when tested against the matched virus, although these antibodies did not always confer cross-neutralization. For one plasma, this activity was mapped to a site overlapping the CD4-induced (CD4i) epitope and CD4bs. Anti-membrane-proximal external region (MPER) ( r = 0.69; P < 0.001) and anti-CD4i ( r = 0.49; P < 0.001) antibody titers were found to be correlated with the neutralization breadth. These anti-MPER antibodies were not 4E10- or 2F5-like but spanned the 4E10 epitope. Furthermore, we found that anti-cardiolipin antibodies were correlated with the neutralization breadth ( r = 0.67; P < 0.001) and anti-MPER antibodies ( r = 0.6; P < 0.001). Our study suggests that more than one epitope on the envelope glycoprotein is involved in the cross-reactive neutralization elicited during natural HIV-1 infection, many of which are yet to be determined, and that polyreactive antibodies are possibly involved in this phenomenon.

Background CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT ( r = −0.28, p = 0.0001) and SRWA ( r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

The characterization of the cross-reactive, or heterologous, neutralizing antibody responses developed during human immunodeficiency virus type 1 (HIV-1) infection and the identification of factors associated with their generation are relevant to the development of an HIV vaccine. We report that in healthy HIV-positive, antiretroviral-naïve subjects, the breadth of plasma heterologous neutralizing antibody responses correlates with the time since infection, plasma viremia levels, and the binding avidity of anti-Env antibodies. Anti-CD4-binding site antibodies are responsible for the exceptionally broad cross-neutralizing antibody responses recorded only in rare plasma samples. However, in most cases examined, antibodies to the variable regions and to the CD4-binding site of Env modestly contributed in defining the overall breadth of these responses. Plasmas with broad cross-neutralizing antibody responses were identified that targeted the gp120 subunit, but their precise epitopes mapped outside the variable regions and the CD4-binding site. Finally, although several plasmas were identified with cross-neutralizing antibody responses that were not directed against gp120, only one plasma with a moderate breadth of heterologous neutralizing antibody responses contained cross-reactive neutralizing antibodies against the 4E10 epitope, which is within the gp41 transmembrane subunit. Overall, our study indicates that more than one pathway leads to the development of broad cross-reactive neutralizing antibodies during HIV infection and that the virus continuously escapes their action.

Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs) that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected subjects should assist in the design of vaccines to elicit similar responses. Here, we investigated the activities of a panel of 24 broadly neutralizing plasmas from subtype B- and C-infected donors using a series of complementary mapping methods, focusing mostly on JR-FL as a prototype subtype B primary isolate. Adsorption with gp120 immobilized on beads revealed that an often large but variable fraction of plasma neutralization was directed to gp120 and that in some cases, neutralization was largely mediated by CD4 binding site (CD4bs) Abs. The results of a native polyacrylamide gel electrophoresis assay using JR-FL trimers further suggested that half of the subtype B and a smaller fraction of subtype C plasmas contained a significant proportion of NAbs directed to the CD4bs. Anti-gp41 neutralizing activity was detected in several plasmas of both subtypes, but in all but one case, constituted only a minor fraction of the overall neutralization activity. Assessment of the activities of the subtype B plasmas against chimeric HIV-2 viruses bearing various fragments of the membrane proximal external region (MPER) of HIV-1 gp41 revealed mixed patterns, implying that MPER neutralization was not dominated by any single specificity akin to known MPER-specific monoclonal Abs. V3 and 2G12-like NAbs appeared to make little or no contribution to JR-FL neutralization titers. Overall, we observed significant titers of anti-CD4bs NAbs in several plasmas, but approximately two-thirds of the neutralizing activity remained undefined, suggesting the existence of NAbs with specificities unlike any characterized to date.

A questionnaire was mailed to 300 Iowa family physicians to determine the influence of a prior psychiatric history on decision making. The response rate was 77%. Respondents were less likely to believe that a patient had serious illness when presenting with a severe headache or abdominal pain if the patient had a prior history of depression ( P < .05) or prior history of somatic complaints ( P < .05), compared with a patient with no past history. Respondents were less likely to report that they would order testing for a patient with headache or abdominal pain if the patient had a history of depression ( P < .05, P = .08, respectively) or somatic complaints ( P < .01). Differences in likelihood of ordering tests were not significant after adjusting for differences in estimated probability of disease. We conclude that physicians respond differently to patients with psychiatric illness because of their estimation of pretest probability of disease rather than bias. We conclude that past psychiatric history influences physicians' estimation of disease presence and willingness to order tests.

Background: The V3 loop of the HIV-1 envelope (Env) glycoprotein gp120 was identified as the ‘‘principal neutralizing domain’’ of HIV-1, but has been considered too variable to serve as a neutralizing antibody (Ab) target. Structural and immunochemical data suggest, however, that V3 contains conserved elements which explain its role in binding to virus coreceptors despite its sequence variability. Despite this evidence of V3 conservation, the ability of anti-V3 Abs to neutralize a significant proportion of HIV-1 isolates from different subtypes (clades) has remained controversial. Methods: HIV-1 neutralization experiments were conducted in two independent laboratories to test human anti-V3 monoclonal Abs (mAbs) against pseudoviruses (psVs) expressing Envs of diverse HIV-1 subtypes from subjects with acute and chronic infections. Neutralization was defined by 50% inhibitory concentrations (IC50), and was statistically assessed based on the area under the neutralization titration curves (AUC). Results: Using AUC analyses, statistically significant neutralization was observed by $1 anti-V3 mAbs against 56/98 (57%) psVs expressing Envs of diverse subtypes, including subtypes A, AG, B, C and D. Even when the 10 Tier 1 psVs tested were excluded from the analysis, significant neutralization was detected by $1 anti-V3 mAbs against 46/88 (52%) psVs from diverse HIV-1 subtypes. Furthermore, 9/24 (37.5%) Tier 2 viruses from the clade B and C standard reference panels were neutralized by $1 anti-V3 mAbs. Each anti-V3 mAb tested was able to neutralize 28–42% of the psVs tested. By IC50 criteria, 40/98 (41%) psVs were neutralized by $1 anti-V3 mAbs. Conclusions: Using standard and new statistical methods of data analysis, 6/7 anti-V3 human mAbs displayed cross-clade neutralizing activity and revealed that a significant proportion of viruses can be neutralized by anti-V3 Abs. The new statistical method for analysis of neutralization data provides many advantages to previously used analyses.