Publications

Energy-time entangled photons are critical in many quantum optical phenomena and have emerged as important elements in quantum information protocols. Entanglement in this degree of freedom often manifests itself on ultrafast time scales, making it very difficult to detect, whether one employs direct or interferometric techniques, as photon-counting detectors have insufficient time resolution. Here, we implement ultrafast photon counters based on nonlinear interactions and strong femtosecond laser pulses to probe energy-time entanglement in this important regime. Using this technique and single-photon spectrometers, we characterize all the spectral and temporal correlations of two entangled photons with femtosecond resolution. This enables the witnessing of energy-time entanglement using uncertainty relations and the direct observation of nonlocal dispersion cancellation on ultrafast time scales. These techniques are essential to understand and control the energy-time degree of freedom of light for ultrafast quantum optics.

OBJECTIVES: To estimate the prevalence and consequences of receiving prescription opioids from both the Department of Veterans Affairs (VA) and Medicare Part D.

METHODS: Among US veterans enrolled in both VA and Part D filling 1 or more opioid prescriptions in 2012 (n = 539 473), we calculated 3 opioid safety measures using morphine milligram equivalents (MME): (1) proportion receiving greater than 100 MME for 1 or more days, (2) mean days receiving greater than 100 MME, and (3) proportion receiving greater than 120 MME for 90 consecutive days. We compared these measures by opioid source.

RESULTS: Overall, 135 643 (25.1%) veterans received opioids from VA only, 332 630 (61.7%) from Part D only, and 71 200 (13.2%) from both. The dual-use group was more likely than the VA-only group to receive greater than 100 MME for 1 or more days (34.3% vs 10.9%; adjusted risk ratio [ARR] = 3.0; 95% confidence interval [CI] = 2.9, 3.1), have more days with greater than 100 MME (42.5 vs 16.9 days; adjusted difference = 16.4 days; 95% CI = 15.7, 17.2), and to receive greater than 120 MME for 90 consecutive days (7.8% vs 3.1%; ARR = 2.2; 95% CI = 2.1, 2.3).

CONCLUSIONS: Among veterans dually enrolled in VA and Medicare Part D, dual use of opioids was associated with more than 2 to 3 times the risk of high-dose opioid exposure.

High-dimensional quantum information processing promises capabilities beyond the current state of the art, but addressing individual information-carrying modes presents a significant experimental challenge. Here we demonstrate effective high-dimensional operations in the time-frequency domain of nonclassical light. We generate heralded photons with tailored temporal-mode structures through the pulse shaping of a broadband parametric down-conversion pump. We then implement a quantum pulse gate, enabled by dispersion-engineered sum-frequency generation, to project onto programmable temporal modes, reconstructing the quantum state in seven dimensions. We also manipulate the time-frequency structure by selectively removing temporal modes, explicitly demonstrating the effectiveness of engineered nonlinear processes for the mode-selective manipulation of quantum states.

OBJECTIVE: Patient refusal of and nonadherence to treatment with disease-modifying antirheumatic drugs (DMARDs) can adversely affect disease outcomes in rheumatoid arthritis (RA). This qualitative study describes how RA patients' feelings in response to experiences and information affected their decisions to accept (agree to adopt, initiate, and implement) or resist (refuse, avoid, and discontinue) DMARD treatment regimens.

METHODS: A total of 48 RA patients were interviewed about their experiences making decisions about DMARDs. The interviews were transcribed, coded, and analyzed for themes related to their internal motivations for accepting or resisting treatment regimens, using a narrative analysis approach.

RESULTS: In addition to feelings about the necessity and dangers of medications, patients' feelings towards their identity as an ill person, the act of taking medication, and the decision process itself were important drivers of patient's decisions. For patients' motivations to accept treatment regimens, 2 themes emerged: a desire to return to a normal life, and fear of future disability due to RA. For motivations to resist treatment regimens, 5 themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.

CONCLUSION: Feelings in response to experiences and information played a major role in how patients weighed the benefits and costs of treatment options, suggesting that addressing patients' feelings may be important when rheumatologists counsel about therapeutic options. Further research is needed to learn how best to address patients' feelings throughout the treatment decision-making process.

By projecting onto complex optical mode profiles, it is possible to estimate arbitrarily small separations between objects with quantum-limited precision, free of uncertainty arising from overlapping intensity profiles. Here we extend these techniques to the time-frequency domain using mode-selective sum-frequency generation with shaped ultrafast pulses. We experimentally resolve temporal and spectral separations between incoherent mixtures of single-photon level signals ten times smaller than their optical bandwidths with a tenfold improvement in precision over the intensity-only Cramér-Rao bound.

BACKGROUND: Sexually transmitted infection (STI) screening prevents complications and is cost-effective. Annual screening is recommended in sexually active women below 25 years and older women at increased risk. Cervical cancer (CC) screening guideline changes in 2009 and 2012 recommended less frequent screening, causing concern that STI screening would decrease. Pennsylvania Medicaid implemented a family planning program in 2007 which covered women's health services (including STI testing) for uninsured women. It is unclear how STI screening was affected by these countervailing forces.

OBJECTIVE: The main objective of this study was to assess STI screening before and after CC screening guideline changes and family planning program implementation, and to determine factors associated with STI screening.

RESEARCH DESIGN: This study was an observational cross-sectional study of Pennsylvania Medicaid administrative claims from 2007 to 2013.

SUBJECTS: Sixteen-year-old to 30-year-old women enrolled in Pennsylvania Medicaid.

MEASURES: Annual STI screening, defined as receipt of ≥1 STI test in respective 1-year periods.

RESULTS: Our population included 1,226,079 women-years for 467,143 women. STI screening increased by 48% between 2007 and 2011, and stabilized by 2013. Odds for STI screening were higher among black compared with white women [adjusted odds ratio (AOR), 2.56; 95% confidence interval (CI), 2.60-3.10]; Hispanic compared with non-Hispanic women (AOR, 1.42; 95% CI, 1.39-1.46); family planning program enrollees (AOR, 1.42; 95% CI, 1.40-1.45); and urban compared with rural residents (AOR, 1.05; 95% CI, 1.03-1.06).

CONCLUSIONS: STI screening dramatically increased between 2007 and 2011. Potential reasons are family planning program implementation, increased urine/vaginal testing, and reporting improvements. It is reassuring that STI screening did not decrease despite CC screening guideline changes. Between 2011 and 2013, rates stabilized at 45% among all women and 60% among sexually active women below 25 years, suggesting opportunities for improvement.

OBJECTIVE: Guidelines recommend that rheumatoid arthritis (RA) patients with moderate-to-high disease activity (MHDAS) adjust disease-modifying antirheumatic drug (DMARD) therapy at least every 3 months until reaching low disease activity or remission (LDAS). We examined how quickly RA patients with MHDAS adjust DMARD therapy in clinical practice, and whether those who adjust DMARDs within 90 days in response to MHDAS reach LDAS sooner.

METHODS: We identified RA patients with MHDAS in the University of Pittsburgh Rheumatoid Arthritis Comparative Effectiveness Research registry, and conducted a competing risks regression on time to DMARD therapy adjustment and a Cox regression on time to LDAS.

RESULTS: We identified 538 eligible subjects with 943.5 patient-years of followup. Sixty percent of patients with persistent MHDAS adjusted DMARDs within 90 days. Among all subjects, median times to DMARD adjustment and LDAS were 154 (interquartile range [IQR] 1-706) days and 301 (IQR 140-706) days, respectively. Being elderly (subdistribution hazard ratio [SHR] 0.61, P = 0.02), lower baseline disease activity (SHR 0.72, P < 0.01), longer duration of RA (SHR 0.98, P < 0.01), and biologic use (SHR 0.71, P < 0.01) were significantly associated with longer times to therapy adjustment. African American race (hazard ratio [HR] 0.63, P = 0.01), higher baseline disease activity (HR 0.75, P < 0.01), and not adjusting DMARD therapy within 90 days (HR 0.76, P = 0.01) were associated with longer times to LDAS.

CONCLUSION: Adjusting DMARDs within 90 days was associated with shorter times to LDAS, but many patients with persistent MHDAS waited >90 days to adjust DMARDs. Interventions are needed to address the timeliness of DMARD adjustments for RA patients with MHDAS.

Although physicians learn about new medical technologies from their peers, the magnitude and source of peer influence is unknown. We estimate the effect of peer adoption of three first-in-class medications (dabigatran, sitigliptin, and aliskiren) on physicians' own adoption of those medications. We included 11,958 physicians in Pennsylvania prescribing anticoagulant, antidiabetic, and antihypertensive medications. We constructed 4 types of peer networks based on shared Medicare and Medicaid patients, medical group affiliation, hospital affiliation, and medical school/residency training. Instrumental variables analysis was used to estimate the causal effect of peer adoption (fraction of peers in each network adopting the new drug) on physician adoption (prescribing at least the median number prescriptions within 15 months of the new drug's introduction). We illustrate how physician network position can inform targeting of interventions to physicians by computing a social multiplier. Dabigatran was adopted by 25.2%, sitagliptin by 24.5% and aliskiren by 8.3% of physicians. A 10-percentage point increase in peer adoption in the patient-sharing network led to a 5.90% (SE = 1.50%, p<0.001) increase in physician adoption of dabigatran, 8.32% (SE = 1.51%, p<0.001) increase in sitagliptin, and 7.84% increase in aliskiren adoption (SE = 2.93%, p<0.001). Peer effects through shared hospital affiliation were positive but not significant, and medical group and training network effects were not reliably estimated. Physicians in the top decile of patient-sharing network peers were estimated to have nearly 2-fold stronger influence on their peers' adoption compared to physicians in the top decile of prescribing volume. Limitations include lack of detailed clinical information and pharmaceutical promotion, variables which may influence physician adoption but which are unlikely to bias our peer effect estimates. Peer adoption, especially by those with whom physicians share patients, strongly influenced physician adoption of new drugs. Our study shows the potential for using information on physician peer networks to improve technology diffusion.

BACKGROUND: The Pharmacy Quality Alliance (PQA) recently developed 3 quality measures for prescribing opioids: high dosages, multiple providers and pharmacies, and concurrent use of opioids and benzodiazepines.

OBJECTIVE: To examine the prevalence of the PQA measures and identify the patient demographic and health characteristics associated with the measures.

METHODS: We conducted a cross-sectional analysis using Pennsylvania Medicaid data (2013-2015). We limited our analyses to noncancer patients who were aged 18-64 years and not dual-eligible for Medicare/Medicaid. Per PQA specifications, patients were required to possess ≥ 2 opioid prescriptions for ≥ 15 days annual supply each year. Outcome measures included (a) high dosages, defined as > 120 morphine milligram equivalents for ≥ 90 consecutive days; (b) multiple providers/pharmacies, defined as receiving opioid prescriptions from ≥ 4 providers and ≥ 4 pharmacies; and (c) concurrent use of opioids and benzodiazepines, defined as ≥ 30 cumulative days of overlapping opioids and benzodiazepines among individuals having ≥ 2 opioid and ≥ 2 benzodiazepine fills. Patient characteristics assessed included demographics; other medication use; and physical, mental, and behavioral health comorbidities. We present descriptive and multivariable statistical analyses of the data to describe trends in quality measure prevalence and associations with enrollee health characteristics.

RESULTS: Numbers of enrollees meeting inclusion criteria ranged from 73,082 in 2013 to 85,710 in 2015. From 2013 to 2015, high dosage prevalence increased from 5.1% to 5.5%; the use of multiple providers/pharmacies decreased from 7.1% to 5.0%; and concurrent use of opioids and benzodiazepines decreased from 29.1% to 28.4% (all P < 0.05). A substantial portion of patients with > 1 PQA measure from 2013 to 2015 was eligible for Medicaid because of disability (41.8%-81.9%). Enrollees with opioid use disorder were more likely to have high dosages (adjusted odds ratio [AOR] = 2.01, 95% CI = 1.83-2.21). Enrollees with anxiety and mood disorders were more likely to have multiple providers/pharmacies (anxiety: AOR = 1.54, 95% CI = 1.43-1.65; mood: AOR = 1.15, 95% CI = 1.06-1.25) and concurrent use of opioids and benzodiazepines (anxiety: AOR = 3.50, 95% CI = 3.38-3.63; mood: AOR = 1.42, 95% CI = 1.36-1.48).

CONCLUSIONS: Given high levels of eligibility based on disability and the prevalence of mood, anxiety, and opioid use disorders among those identified by the quality measures, providers may require additional support to care for this patient population.

DISCLOSURES: This project was supported by a grant from the Centers for Disease Control and Prevention and was also supported by an intergovernmental agreement between the Pennsylvania Department of Human Services and the University of Pittsburgh. Lo-Ciganic was supported by the University of Arizona Health Sciences Career Development Award. The other authors have nothing to disclose. The conclusions, findings, and opinions expressed by authors contributing to this article do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the Commonwealth of Pennsylvania. A portion of these results was presented at the Association for Medical Education and Research in Substance Abuse 41st National Conference; November 2-4, 2017; Washington, DC.