Introduction

Human immunodeficiency virus (HIV)-infected patients in the current treatment era can achieve normal life expectancies but experience a high degree of medical and psychiatric comorbidity. Impaired physical function and pain, often in the context of mood disorders and substance abuse, are common in HIV-infected patients. The objective of this study was to investigate the relationship of pain, a modifiable condition, to functional impairment in HIV-infected patients, independent of mood disorders and substance abuse.

Methods

Participants in a prospective cohort of HIV-infected patients at the University of Alabama at Birmingham were included. Patient-reported outcome measures were used to cross-sectionally assess pain and physical function (EuroQOL), mood disorders (PHQ), and substance abuse (ASSIST). Univariate and multivariable models were built with pain as the principal independent variable of interest and three domains of physical function (mobility, self-care, and usual activities) as outcomes. Covariates included mood, substance abuse, age, race, sex, insurance status, HIV transmission risk factor, and CD4+ T-cell count.

Results

Among 1,903 participants, 693 (37%) reported pain; 509 (27%) had a mood disorder; and 157 (8.4%) reported current substance abuse. In multivariable models, pain was independently associated with increased odds of impairment in all three domains of physical function investigated-mobility (aOR 10.5, 95% CI 7.6-14.6), self-care (aOR 4.1, 95% CI 2.2-7.4), and usual activities (aOR 5.4, 95% CI 4.0-7.4).

Discussion

Pain was associated with substantially increased odds of impairment in physical function. Pain should be an important consideration in HIV primary care. Interventions to address pain and impaired physical function should be investigated.

BACKGROUND: Anal cancer rates are higher for human immunodeficiency virus (HIV)-infected adults than for uninfected adults. Limited published data exist characterizing the incidence of precursor lesions detected by anal cytology. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in 4 US cities. At baseline and annually thereafter, each participant completed a behavioral questionnaire, and healthcare professionals collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. RESULTS: Among 243 participants with negative baseline results of anal cytology, 37% developed abnormal cytology findings (incidence rate, 13.9 cases/100 person-years of follow-up; 95% confidence interval [CI], 11.3-16.9) over a median follow-up duration of 2.1 years. Rates among men having sex with men, among women, and among men having sex with women were 17.9 cases/person-years of follow-up (95% CI, 13.9-22.7), 9.4 cases/person-years of follow-up (95% CI, 5.6-14.9), and 8.9 cases/person-years of follow-up (95% CI, 4.8-15.6), respectively. In multivariable analysis, the number of persistent high-risk HPV types (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.01-1.36), persistent high-risk HPV types except 16 or 18 (aHR, 2.46; 95% CI, 1.31-4.60), and persistent types 16 or 18 (aHR, 3.90; 95% CI, 1.78-8.54) remained associated with incident abnormalities. CONCLUSIONS: The incidence of abnormal anal cytology findings was high and more likely to develop among persons with persistent high-risk HPV.

Background

Anal cancer rates are higher for human immunodeficiency virus (HIV)-infected adults than for uninfected adults. Limited published data exist characterizing the incidence of precursor lesions detected by anal cytology.

Methods

The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in 4 US cities. At baseline and annually thereafter, each participant completed a behavioral questionnaire, and healthcare professionals collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping.

Results

Among 243 participants with negative baseline results of anal cytology, 37% developed abnormal cytology findings (incidence rate, 13.9 cases/100 person-years of follow-up; 95% confidence interval [CI], 11.3-16.9) over a median follow-up duration of 2.1 years. Rates among men having sex with men, among women, and among men having sex with women were 17.9 cases/person-years of follow-up (95% CI, 13.9-22.7), 9.4 cases/person-years of follow-up (95% CI, 5.6-14.9), and 8.9 cases/person-years of follow-up (95% CI, 4.8-15.6), respectively. In multivariable analysis, the number of persistent high-risk HPV types (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.01-1.36), persistent high-risk HPV types except 16 or 18 (aHR, 2.46; 95% CI, 1.31-4.60), and persistent types 16 or 18 (aHR, 3.90; 95% CI, 1.78-8.54) remained associated with incident abnormalities.

Conclusions

The incidence of abnormal anal cytology findings was high and more likely to develop among persons with persistent high-risk HPV.

Background

Meta-analyses of general population studies report mean low-density lipoprotein cholesterol (LDL-C) reductions of 30% to <50% with moderate-intensity and ≥50% with high-intensity statins. Persons living with human immunodeficiency virus (PLWH) are at high risk for atherosclerotic cardiovascular disease (ASCVD), yet many have elevated LDL-C.

Objective

To evaluate LDL-C response after statin initiation among PLWH.

Methods

We conducted a retrospective cohort study of PLWH initiating statins between 2009 and 2013 (N = 706). Patients were categorized into mutually exclusive groups in the following hierarchy: history of coronary heart disease (CHD), diabetes, prestatin LDL-C ≥190 mg/dL, 10-year predicted ASCVD risk ≥7.5%, and none of the above (ie, unknown statin indication). The primary outcome was a ≥30% reduction in LDL-C after statin initiation.

Results

Among patients initiating statins, 5.8% had a history of CHD, 13.6% had diabetes, 6.2% had LDL-C ≥190 mg/dL, 35.4% had 10-year ASCVD risk ≥7.5%, and 39.0% had an unknown statin indication. Among patients with a history of CHD, 31.7% achieved a ≥30% LDL-C reduction compared with 25.0%, 59.1%, and 33.9% among those with diabetes, LDL-C ≥190 mg/dL, and 10-year ASCVD risk ≥7.5%, respectively. In multivariable adjusted analyses and compared to patients with an unknown statin indication, LDL-C ≥ 190 mg/dL was associated with a prevalence ratio for an LDL-C reduction ≥30% of 1.81 (95% confidence interval, 1.34-2.45), whereas no statistically significant association was present for history of CHD, diabetes, and 10-year ASCVD risk ≥7.5%.

Conclusion

A low percentage of PLWH achieved the expected reductions in LDL-C after statin initiation, highlighting an unmet need for ASCVD risk reduction.

Despite its potential to improve metabolic health outcomes, longitudinal physical activity (PA) patterns and their association with cardiometabolic disease among people living with HIV (PLWH) have not been well characterized. We investigated this relationship among PLWH in the Centers for AIDS Research Network of Integrated Clinical Systems with at least one PA self-report between 2008 and 2015. The 4-item Lipid Research Clinics PA instrument was used to categorize habitual PA levels as: Very Low, Low, Moderate, or High. We analyzed demographic differences in PA patterns. Multivariable generalized estimating equation regression models were fit to assess longitudinal associations of PA with blood pressure, lipid, and glucose levels. Logistic regression modeling was used to assess the odds of being diagnosed with obesity, cardiovascular disease (CVD), cerebrovascular disease, hypertension, diabetes, or multimorbidity. A total of 40,462 unique PA assessments were provided by 11,719 participants. Only 13% of PLWH reported High PA, while 68% reported Very Low/Low PA at baseline and did not increase PA levels during the study period. Compared to those reporting High PA, participants with Very Low PA had almost 2-fold increased risk for CVD. Very Low PA was also associated with several risk factors associated with CVD, most notably elevated triglycerides (odds ratio 25.4), obesity (odds ratio 1.9), hypertension (odds ratio 1.4), and diabetes (odds ratio 2.3; all p < 0.01). Low levels of PA over time among PLWH are associated with increased cardiometabolic disease risk.

Muon beams of low emittance provide the basis for the intense, well-characterized neutrino beams necessary to elucidate the physics of flavor at a neutrino factory and to provide lepton-antilepton collisions at energies of up to several TeV at a muon collider. The international Muon Ionization Cooling Experiment (MICE) aims to demonstrate ionization cooling, the technique by which it is proposed to reduce the phase-space volume occupied by the muon beam at such facilities. In an ionization-cooling channel, the muon beam passes through a material in which it loses energy. The energy lost is then replaced using rf cavities. The combined effect of energy loss and reacceleration is to reduce the transverse emittance of the beam (transverse cooling). A major revision of the scope of the project was carried out over the summer of 2014. The revised experiment can deliver a demonstration of ionization cooling. The design of the cooling demonstration experiment will be described together with its predicted cooling performance.

The Muon Ionization Cooling Experiment (MICE) collaboration seeks to demonstrate the feasibility of ionization cooling, the technique by which it is proposed to cool the muon beam at a future neutrino factory or muon collider. The emittance is measured from an ensemble of muons assembled from those that pass through the experiment. A pure muon ensemble is selected using a particle-identification system that can reject efficiently both pions and electrons. The position and momentum of each muon are measured using a high-precision scintillating-fibre tracker in a 4 T solenoidal magnetic field. This paper presents the techniques used to reconstruct the phase-space distributions in the upstream tracking detector and reports the first particle-by-particle measurement of the emittance of the MICE Muon Beam as a function of muon-beam momentum.

The Muon Ionization Cooling Experiment (MICE) will perform a detailed study of ionization cooling to evaluate the feasibility of the technique. To carry out this program, MICE requires an efficient particle-identification (PID) system to identify muons. The Electron-Muon Ranger (EMR) is a fully-active tracking-calorimeter that forms part of the PID system and tags muons that traverse the cooling channel without decaying. The detector is capable of identifying electrons with an efficiency of 98.6%, providing a purity for the MICE beam that exceeds 99.8%. The EMR also proved to be a powerful tool for the reconstruction of muon momenta in the range 100-280 MeV/c.

The use of accelerated beams of electrons, protons or ions has furthered the development of nearly every scientific discipline. However, high-energy muon beams of equivalent quality have not yet been delivered. Muon beams can be created through the decay of pions produced by the interaction of a proton beam with a target. Such 'tertiary' beams have much lower brightness than those created by accelerating electrons, protons or ions. High-brightness muon beams comparable to those produced by state-of-the-art electron, proton and ion accelerators could facilitate the study of lepton-antilepton collisions at extremely high energies and provide well characterized neutrino beams^1-6. Such muon beams could be realized using ionization cooling, which has been proposed to increase muon-beam brightness^7,8. Here we report the realization of ionization cooling, which was confirmed by the observation of an increased number of low-amplitude muons after passage of the muon beam through an absorber, as well as an increase in the corresponding phase-space density. The simulated performance of the ionization cooling system is consistent with the measured data, validating designs of the ionization cooling channel in which the cooling process is repeated to produce a substantial cooling effect^9-11. The results presented here are an important step towards achieving the muon-beam quality required to search for phenomena at energy scales beyond the reach of the Large Hadron Collider at a facility of equivalent or reduced footprint⁶.

The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240 MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than ∼1% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is fπ < 1.4% at 90% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling.