Opioid and Non-Opioid Pharmacotherapy Use for Pain Management Among Privately Insured Pediatric Patients With Cancer in the United States.

BACKGROUND: This study examined the trends and patterns of opioid and non-opioid pharmacotherapy use among a large national sample of privately insured pediatric patients with cancer in the United States. MATERIALS AND METHODS: We identified pediatric (aged < 21) patients diagnosed with central nervous system (CNS), lymphoma, gonadal, leukemia, or bone cancer from MarketScan data 2005-2019. We examined the proportion of patients who filled a prescription for the following 5 types of pharmacotherapy: opioid, anticonvulsant, non-steroidal anti-inflammatory drug (NSAID), antidepressant, and muscle relaxant during active cancer treatment. We assessed the trends and patterns in pharmacotherapy using multivariable logistic regressions. RESULTS: Among 4174 patients included, 2979 (71%) had an opioid prescription; 746 (18%), 384 (9%), 202 (5%), and 169 (4%) had anticonvulsant, NSAID, antidepressant and muscle relaxant prescriptions, respectively. Multivariable logistic regression showed a nonlinear trend in the use of opioids among pediatric patients with cancer over time such that use slightly increased until 2012 (OR of 1.40 [95% CI, 1.12-1.73] for 2012 vs. 2006) but then decreased thereafter (OR of 0.51 [0.37-0.68] for 2018 vs. 2012). The use of anticonvulsants, NSAIDs, and muscle relaxants increased significantly linearly over time (all P < .005). CONCLUSION: There has been a downward trend in the use of opioids in recent years among pediatric patients with cancer and an upward trend in the use of non-opioid pharmacotherapy for pain management potentially as an alternative to opioids.

Race, Ethnicity, and Intensive Care Utilization for Common Pediatric Diagnoses: U.S. Pediatric Health Information System 2019 Database Study.

OBJECTIVES: Racial and ethnic disparities in healthcare delivery for acutely ill children are pervasive in the United States; it is unknown whether differential critical care utilization exists. DESIGN: Retrospective study of the Pediatric Health Information System (PHIS) database. SETTING: Multicenter database of academic children's hospitals in the United States. PATIENTS: Children discharged from a PHIS hospital in 2019 with one of the top ten medical conditions where PICU utilization was present in greater than or equal to 5% of hospitalizations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Race and ethnicity categories included Asian, Black, Hispanic, White, and other. Primary outcomes of interest were differences in rate of PICU admission, and for children requiring PICU care, total hospital length of stay (LOS). One-quarter (n = 44,200) of the 178,134 hospital discharges included a PICU admission. In adjusted models, Black children had greater adjusted odds ratio (aOR [95% CI]) of PICU admission in bronchiolitis (aOR, 1.08 [95% CI, 1.02-1.14]; p = 0.01), respiratory failure (aOR, 1.18 [95% CI, 1.10-1.28]; p < 0.001), seizure (aOR, 1.28 [95% CI, 1.08-1.51]; p = 0.004), and diabetic ketoacidosis (DKA) (aOR, 1.18 [95% CI, 1.05-1.32]; p = 0.006). Together, Hispanic, Asian, and other race children had greater aOR of PICU admission in five of the diagnostic categories, compared with White children. The geometric mean (± sd) hospital LOS ranged from 47.7 hours (± 2.1 hr) in croup to 206.6 hours (± 2.8 hr) in sepsis. After adjusting for demographics and illness severity, non-White children had longer LOS in respiratory failure, pneumonia, DKA, and sepsis. CONCLUSIONS: The need for critical care to treat acute illness in children may be inequitable. Additional studies are needed to understand and eradicate differences in PICU utilization based on race and ethnicity.

Moving toward Equitable Care for Sleep Apnea in the United States: Positive Airway Pressure Adherence Thresholds: An Official American Thoracic Society Policy Statement.

Background: Positive airway pressure (PAP) is a highly effective treatment for obstructive sleep apnea (OSA), but adherence limits its efficacy. In addition, coverage of PAP by CMS (Centers for Medicare & Medicaid Services) and other insurers in the United States depends on adherence. This leaves many beneficiaries without PAP, disproportionally impacting non-white and low socioeconomic position patients with OSA and exacerbating sleep health disparities. Methods: An inter-professional, multidisciplinary, international committee with various stakeholders was formed. Three working groups (the historical policy origins, impact of current policy, and international PAP coverage models) met and performed literature reviews and discussions. Using surveys and an iterative discussion-based consensus process, the policy statement recommendations were created. Results: In this position paper, we advocate for policy change to CMS PAP coverage requirements to reduce inequities and align with patient-centered goals. We specifically call for eradicating repeat polysomnography, eliminating the 4-hour rule, and focusing on patient-oriented outcomes such as improved sleepiness and sleep quality. Conclusions: Modifications to the current policies for PAP insurance coverage could improve health disparities.

Patients' willingness to pay for naloxone: A national cross-sectional survey of prescription opioid users with chronic pain in the United States.

BACKGROUND: Millions of U.S. people have been heavily affected by opioids. In March 2023, the Food and Drug Administration approved naloxone as an over-the-counter medication. This has allowed more access to patients at high risk of opioid overdose. However, the patient's willingness to pay for naloxone at the pharmacy counter has not been assessed. OBJECTIVES: This study aimed to characterize factors associated with the willingness to pay for naloxone among the patient group. METHODS: A cross-sectional Qualtrics online panel survey instrument was developed. This survey was distributed to patients in the United States, aged ≥ 18 years, with any chronic pain and taking opioids. The survey included demographics, and clinical characteristics (pain assessment, opioid use, and knowledge of naloxone). In addition, willingness to pay was assessed using a 7-point Likert scale ranging from strongly disagree to strongly agree. An ordinal logistic regression model was used to examine demographic and clinical characteristics. RESULTS: A total of 549 subjects completed the survey (women [53.01%], white or Caucasian (83.61%), age mean [SD] 44 [13]). Women were associated with less willingness to pay (adjusted odds ratio [aOR] 0.685 [95% CI 0.478-0.983], P = 0.0403). Compared with the high household income group (≥ $150,000), low household income ≤ $25,000 (aOR 0.326 [95% CI 0.160-0.662], P = 0.0020) or income between $25,000 and 74,999 (aOR 0.369 [95% CI 0.207-0.657], P = 0.0007) was associated with less likelihood of willing to pay. Patients with a previous diagnosis of obstructive sleep apnea were associated with a higher likelihood of willingness to pay (aOR 1.685 [95% CI 1.138-2.496], P = 0.0092). Each unit increase in pain was also associated with a higher likelihood of willingness to pay (aOR 1.247 [95% CI 1.139-1.365], P < 0.0001). CONCLUSIONS: Demographics and clinical factors were associated with willingness to pay for naloxone. This study's findings are useful in the development of interventions to address pharmacy-based naloxone distribution programs.

Management of metastatic melanoma in Texas: disparities in the utilization of immunotherapy following the regulatory approval of immune checkpoint inhibitors.

BACKGROUND: The utilization of modern-immunotherapies, notably immune checkpoint inhibitors (ICIs), has increased markedly in patients with metastatic melanoma over the past decade and are recommended as standard treatment. Given their increasing adoption in routine care for melanoma, understanding patient access to immunotherapy and patterns of its use in Texas is crucial as it remains one of the few states without Medicaid expansion and with high rates of the uninsured population. The objectives of this study were to examine the trend in the utilization of immunotherapy and to determine factors associated with immunotherapy utilization among patients with metastatic melanoma in the era of ICIs in Texas. METHODS: A retrospective cohort study was conducted using the Texas Cancer Registry (TCR) database. The cohort comprised of adult (≥ 18 years) patients with metastatic melanoma diagnosed between June 2011 and December 2018. The trend in immunotherapy utilization was assessed by determining the proportion of patients receiving immunotherapy each year. The Average Annual Percent Change (AAPC) in immunotherapy utilization was assessed using joinpoint regression, while multivariable logistic regression was used to determine the association between patient characteristics and immunotherapy receipt. RESULTS: A total of 1,795 adult patients with metastatic melanoma were identified from the TCR. Immunotherapy utilization was higher among younger patients, those with no comorbidities, and patients with private insurance. Multivariable analysis showed that the likelihood of receipt of immunotherapy decreased with older age [(adjusted Odds Ratio (aOR), 0.92; 95% CI, 0.89- 0.93, p = 0.001], living in high poverty neighborhood (aOR, 0.52; 95% CI, 0.44 - 0.66, p < 0.0001), having Medicaid (aOR, 0.58; 95% CI, 0.44 - 0.73, p = 0.02), being uninsured (aOR, 0.49; 95% CI, 0.31 - 0.64, p = 0.01), and having comorbidities (CCI score 1: aOR, 0.48; 95% CI, 0.34 - 0.71, p = 0.003; CCI score ≥ 2: aOR, 0.32; 95% CI, 0.16 - 0.56, p < 0.0001). CONCLUSIONS AND RELEVANCE: This cohort study identified sociodemographic and socioeconomic disparities in access to immunotherapy in Texas, highlighting the need for policies such as Medicaid expansion that would increase equitable access to this innovative therapy.

Perception of burden of oral and inhaled corticosteroid adverse effects on asthma-specific quality of life.

BACKGROUND: A multistakeholder core outcome set created for asthma trials showed that asthma-specific quality of life (QoL) was a critically meaningful outcome. However, the definition and measurement methods were undetermined. The adverse effects (AEs) of corticosteroids may be a vital clinical trial outcome. Nevertheless, the AE burden from the patient perspective has not yet been elucidated in an asthma population. OBJECTIVE: To characterize patient burden of AEs in oral (OCS) and inhaled corticosteroids (ICS) and how this relates to QoL within an asthma population. METHODS: We used a convergent parallel mixed-methods design with quantitative surveys of known ICS and OCS AEs that were distributed through the Allergy & Asthma Network database, social channels, and the Asthma UK newsletter. Participants rated the AEs that were (1) most burdensome and (2) most desired to be eliminated. Qualitative interviews and focus groups were performed to better understand patient views on barriers reported in the quantitative data, and to identify patient-important barriers that were not a part of the quantitative survey. RESULTS: The 3 most burdensome AEs for OCS were bone mineral density, infectious complications, and weight gain, whereas weight gain was the most desired to be eliminated. The 3 most burdensome AEs for ICS were pneumonia, hoarse voice, and oral thrush, with concordant results for the most desired to be eliminated. In the focus groups, OCS AEs were concordant with quantitative findings. Focus groups identified unmeasured psychosocial effects, such as embarrassment. CONCLUSION: The most burdensome AEs may not be those that would cause patients to stop therapy. Furthermore, qualitative focus groups suggest a psychosocial burden associated with ICS, which needs further investigation.

Palliative Care Early in the Care Continuum among Patients with Serious Respiratory Illness: An Official ATS/AAHPM/HPNA/SWHPN Policy Statement.

Background: Patients with serious respiratory illness and their caregivers suffer considerable burdens, and palliative care is a fundamental right for anyone who needs it. However, the overwhelming majority of patients do not receive timely palliative care before the end of life, despite robust evidence for improved outcomes. Goals: This policy statement by the American Thoracic Society (ATS) and partnering societies advocates for improved integration of high-quality palliative care early in the care continuum for patients with serious respiratory illness and their caregivers and provides clinicians and policymakers with a framework to accomplish this. Methods: An international and interprofessional expert committee, including patients and caregivers, achieved consensus across a diverse working group representing pulmonary-critical care, palliative care, bioethics, health law and policy, geriatrics, nursing, physiotherapy, social work, pharmacy, patient advocacy, psychology, and sociology. Results: The committee developed fundamental values, principles, and policy recommendations for integrating palliative care in serious respiratory illness care across seven domains: 1) delivery models, 2) comprehensive symptom assessment and management, 3) advance care planning and goals of care discussions, 4) caregiver support, 5) health disparities, 6) mass casualty events and emergency preparedness, and 7) research priorities. The recommendations encourage timely integration of palliative care, promote innovative primary and secondary or specialist palliative care delivery models, and advocate for research and policy initiatives to improve the availability and quality of palliative care for patients and their caregivers. Conclusions: This multisociety policy statement establishes a framework for early palliative care in serious respiratory illness and provides guidance for pulmonary-critical care clinicians and policymakers for its proactive integration.

Experiences with Continuous Positive Airway Pressure Among African American Patients and their Bed Partners.

RATIONALE: Despite having a higher prevalence and severity of obstructive sleep apnea (OSA), African Americans have lower adherence to continuous positive airway pressure (CPAP) compared to other groups. Information regarding challenges faced by African Americans prescribed CPAP are lacking. OBJECTIVES: To determine the barriers and facilitators to optimal management of OSA with CPAP among African Americans and to understand the role bed partners may play. METHODS: We conducted semi-structured in-depth interviews via video conferencing with African American patients of an urban safety-net health care system with OSA prescribed CPAP and their bed partners. Recruitment continued until theoretical saturation was achieved. Verbatim transcripts were analyzed using the principles of thematic analysis. RESULTS: 15 patients (12 women) diagnosed with OSA and prescribed CPAP a mean 2.6 years prior along with 15 bed partners (3 women) were individually interviewed. Four themes emerged regarding impediments to CPAP use: 1) inadequate education and support, 2) CPAP maintenance and hygiene, 3) inconvenient design of CPAP interfaces, and 4) impediment to intimacy. Four themes emerged as facilitators to CPAP use: 1) provider and technical support, 2) properly fitted CPAP masks, 3) active support from partner and family, and 4) experiencing positive results from CPAP. CONCLUSIONS: African American patients with OSA and their bed partners identified several unique barriers and facilitators to CPAP use. Active involvement by bed partners was considered by both patients and partners as helpful in improving CPAP adherence. Interventions to improve OSA outcomes in this population should focus on patients and their bed partners.

Physician perspective on the implementation of risk mitigation strategies when prescribing opioid medications: a qualitative analysis.

OBJECTIVE: To understand the physician perspective on the barriers and facilitators of implementing nine different opioid risk mitigation strategies (RMS) when prescribing opioid medications. METHODS: We created and dispersed a cross-sectional online survey through the Qualtrics© data collection platform among a nationwide sample of physicians licensed to practice medicine in the United States who have prescribed an opioid medication within the past year. The responses were analyzed using a deductive thematic analysis approach based on the Consolidated Framework for Implementation Research (CFIR) to ensure a holistic approach to identifying the barriers and facilitators for each RMS assessed. In concordance with this method, the themes and codes for the thematic analysis were defined prior to the analysis. The five domains within the CFIR were used as themes and the 39 nested constructs were treated as the codes. Two members of the research team independently coded the transcripts and discussed points of disagreement until consensus was reached. All analyses were conducted in ATLAS.ti© V7. RESULTS: The completion rate for this survey was 85.1% with 273 participant responses eligible for analysis. Intercoder reliability was calculated to be 82%. Deductive thematic analysis yielded 2,077 descriptions of factors affecting implementation of the nine RMS. The most salient code across all RMS was Knowledge and Beliefs about the Intervention, which refers to individuals' attitudes towards and value placed on the intervention. Patient Needs and Resources, a code referring to the extent to which patient needs are known and prioritized by the organization, also emerged as a salient code. The physicians agreed that the patient perspective on the issue is vital to the uptake of each of the RMS. CONCLUSIONS: This deductive thematic analysis identified key points for actionable intervention across the nine RMS assessed and established the importance of patient concordance with physicians when deciding on a course of treatment.

Differences in Perceived Threat and Efficacy in Managing Opioid Use Disorder versus Alcohol Use Disorder.

Background: Efforts to increase the availability of Medication Assisted Treatment for alcohol use disorder (AUD) and opioid use disorder (OUD) may be futile if patients lack motivation for recovery and are unwilling to seek treatment. Objectives: In this cross-sectional, online survey, we used the Extended Parallel Process Model (EPPM) to assess how participants at risk of AUD or OUD react to their perceived threat and assess their response to pharmacotherapy as a potential treatment. EPPM constructs were assessed using the Risk Based Diagnosis Scale. Descriptive statistics measure the proportion of treated vs untreated participants. Untreated participants were sorted into one of three groups categorizing perceived threat - low threat appraisal, and danger or fear control. Results: Of 411 total responses, most (n = 293[71.29%]) sorted into the AUD cohort and 118(28.71%) into the OUD cohort. Overall, 104(25.30%) had received treatment and 307(74.70%) didn't. Within the OUD cohort, there were 67 untreated participants - 16(23.88%) exhibited low threat appraisal, 13(19.40%) were likely to undergo fear control, and 38(56.72%) were likely to undergo danger control. Within the AUD cohort, there were 240 untreated participants - 75(31.25%) exhibited low threat appraisal, 100(41.67%) were likely to experience fear control, and 65(27.08%) were likely to experience danger control. Participants in the OUD cohort were more likely to undergo danger control than those in the AUD cohort (χ2 = 19.26, p < 0.05). Conclusions: This study identified perceived threat and efficacy when an individual was at risk of a SUD, but more insight into potential early interventions is needed - particularly in those individuals with polysubstance use disorder.

Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction.

PURPOSE: To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). MATERIALS AND METHODS: A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0-36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. RESULTS: 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. CONCLUSION: An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.

Parents' intention to have their child vaccinated at a community pharmacy: A national cross-sectional survey.

BACKGROUND: During the coronavirus disease 2019 pandemic, pediatric vaccination rates for routine childhood vaccines have been declining. To boost pediatric immunizations, pharmacists in the United States may order and administer age-appropriate vaccines to children of 3 years of age and older without a prescription. OBJECTIVE: The objective of this study was to examine parents' intention to have their young children between 3 and 10 years of age vaccinated in a community pharmacy setting. METHODS: A survey instrument was designed based on the health belief model (HBM). The cross-sectional survey was administered online via Qualtrics Panels to parents in the United States with at least 1 child between the ages of 3 and 10 years. Confirmatory factor analysis was used to estimate the correlation between each of the HBM constructs and a 3-item scale measuring parents' intention to have their children between the ages of 3 and 10 vaccinated in a community pharmacy. RESULTS: There were 416 usable responses collected for an effective response rate of 25.95%. Most participants were white (79.09%) and female (51.44%), and many had a graduate degree (48.32%). More than half of parents (69.7%) indicated they would be willing to have their child vaccinated in a community pharmacy. Intention to have their child vaccinated in a pharmacy was most strongly corrected with health benefit beliefs (ψ 0.79 [95% CI 0.75-0.83]), (ψ 0.86 [95% CI 0.83-0.89])cues to action, and perceived convenience.(ψ 0.71 [95% CI 0.66-0.76]). CONCLUSION: Many parents have high intention to vaccinate their young children in community pharmacies. Parents should be educated and informed about services that community pharmacies offer. Stakeholders need to engage in interventions targeted at promoting health benefits of getting vaccinations at a pharmacy and strong recommendations from health care providers.

Resolvin D2 promotes host defense in a 2 - hit model of sepsis with secondary lung infection.

In the development of sepsis, there is early, massive inflammation which can lead to multiple organ failure. Later there is an immunosuppressed phase where the host is susceptible to secondary infections or is unable to clear existing infection. Specialized Pro-resolving Mediators (SPMs) are endogenously produced lipids which resolve infection by decreasing bacteria load and reducing systemic inflammatory response. There has been little work studying if SPMs given late, can promote host defense. We examined if an SPM, Resolvin D2 (RvD2) could promote host defense in a 2-hit mouse model of cecal ligation and puncture (CLP) sepsis and secondary Pseudomonas aeruginosa lung infection. RvD2 given 48 h after mild CLP (1st hit), increased gene expression of Toll-like receptor-2 (TLR-2) and alveolar macrophage/monocyte phagocytic ability compared to CLP mice given saline vehicle. In this model, RvD2 did not affect plasma IL-6 or IL-10. These effects induced by RvD2, lowered lung bacterial load and decreased mortality after the secondary infection of Pseudomonas aeruginosa (2nd hit). Splenic T-cell numbers were also increased in RvD2 treated mice compared to saline vehicle treated animals. The results suggest that RvD2 promoted mechanisms of host defense in a 2-hit model sepsis and secondary lung infection.

Intention to get naloxone among patients prescribed opioids for chronic pain.

BACKGROUND: Prescription opioids have been increasingly prescribed for chronic pain while the opioid-related death rates grow. Naloxone, an opioid antagonist, is increasingly recommended in these patients, yet there is limited research that investigates the intention to get naloxone. This study aimed to investigate intention toward getting naloxone in patients prescribed opioids for chronic pain and to assess the predictive utility of the theory of reasoned action (TRA) constructs in explaining intention to get naloxone. METHODS: This was a cross-sectional study of a panel of U.S. adult patients prescribed opioids for chronic pain using a Qualtrics®XM survey. These patients participated in the study during February to March 2020. The online internet survey assessed the main outcome of intention to get naloxone and constructs of TRA (attitudes and subjective norms); additional measures assessed the characteristics of patients' opioid overdose risk factors, knowledge of naloxone, and their demographics. The relationship between TRA constructs, namely, attitudes and subjective norms, and the intention variable was examined using logistic regression analyses with the intention outcome contrasted as follows: high intention (scores ≥ 5) and non-high intention (scores < 5). RESULTS: A total of 549 participants completed the survey. Most of them were female (53.01%), White or Caucasian (83.61%), non-Hispanic (87.57%) and had a mean age of 44.16 years (SD = 13.37). Of these, 167 (30.42%) had high intention to get naloxone. The TRA construct of subjective norm was significantly associated with increased likelihood of higher intentions to get naloxone (OR 3.04, 95% CI 2.50-3.70, P < 0.0001). CONCLUSIONS: Our study provides empirical support of the TRA in predicting intention to get naloxone among chronic pain patients currently taking opioids. Subjective norms significantly predicted intention to get naloxone in these patients. The interventions targeting important reference groups of these patients would have greater impact on increasing intention to get naloxone in this population. Future studies should test whether theory-based interventions focusing on strengthening subjective norms increase intention to get naloxone in this population.

Association of cash payment with intensity of opioid prescriptions.

BACKGROUND: It is difficult to track use and outcomes in patients who pay cash for their prescriptions at the pharmacy. In Texas, 14% of all opioid prescriptions are paid with cash, often by uninsured patients and pharmacy shoppers. OBJECTIVE: To evaluate the association of cash payment with intensity of opioid prescriptions. METHODS: Using a prescription drug monitoring program and the U.S. Census data for the 2019 calendar year, this cross-sectional descriptive study analyzed more than 4 million opioid prescriptions in Texas residents aged 18-64 years. The payment type was coded as insurance if the prescription was paid in whole or in part by a health plan and as cash otherwise. Daily morphine milligram equivalent (MME) dose was used to compare the intensity of opioid prescriptions. The association of uninsured rates with mean daily MME and the number of opioid prescriptions paid with cash per 100,000 persons were assessed at a county level. RESULTS: Cash payment was associated with 30% higher mean daily MME (59 vs. 45; P < 0.001) than insurance payment. This difference was driven by the prescriptions for patients aged 25-34 years and from the highest decile of prescribers based on the percentage of opioid prescriptions paid by cash. For instance, cash payment was associated with 82% higher mean daily MME (91 vs. 50; P < 0.001) when patients aged 25-34 years obtained their prescriptions from the highest decile of prescribers. At a county level, uninsured rates were not associated with mean daily MMEs or the number of opioid prescriptions paid with cash. CONCLUSION: Cash payment was associated with a higher intensity of opioid prescriptions, mirroring the rates of drug overdose deaths across the patient age groups. Further research and policy actions need to address unmet pain management needs in uninsured patients and potential pharmacy shopping with cash payment and fraudulent identifications.

The Impact of an Electronic Health Record Intervention on Spirometry Completion in Patients with Chronic Obstructive Pulmonary Disease.

Spirometry is necessary to diagnose chronic obstructive pulmonary disease (COPD), yet a large proportion of patients are diagnosed and treated without having received testing. This study explored whether the effects of interventions using the electronic health record (EHR) to target patients diagnosed with COPD without confirmatory spirometry impacted the incidence rates of spirometry referrals and completions. This retrospective before and after study assessed the impact of provider-facing clinical decision support that identified patients who had a diagnosis of COPD but had not received spirometry. Spirometry referrals, completions, and results were ascertained 1.5 years prior to and 1.5 years after the interventions were initiated. Inhaler prescriptions by class were also tallied. There were 10,949 unique patients with a diagnosis of COPD who were eligible for inclusion. 4,895 patients (44.7%) were excluded because they had completed spirometry prior to the cohort start dates. The pre-intervention cohort consisted of 2,622 patients, while the post-intervention cohort had 3,392. Spirometry referral rates pre-intervention were 20.2% compared to 31.6% post-intervention (p < 0.001). Spirometry completion rates rose from 13.2% pre-intervention to 19.3% afterwards (p < 0.001). 61.7% (585 of 948) had no evidence of airflow obstruction. After excluding patients with a diagnosis of asthma, 25.8% (126 of 488) patients who had no evidence of airflow obstruction had prescriptions for long-acting bronchodilators or inhaled steroids. A concerted EHR intervention modestly increased spirometry referral and completion rates in patients with a diagnosis of COPD without prior spirometry and decreased misclassification of disease.

Lipoxin A4 promotes reduction and antibiotic efficacy against Pseudomonas aeruginosa biofilm.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic bacterium commonly found in wound infections and airways of cystic fibrosis patients. P. aeruginosa readily forms biofilms which can reduce the efficacy of antibiotics used to eradicate the pathogen. We have previously shown that a Specialized Pro-resolving Mediator (SPM), Lipoxin A4 (LxA4) is a quorum sensing inhibitor which can reduce P. aeruginosa virulence. In this study, we examined the direct actions of LxA4 and RvD2 on P. aeruginosa biofilm formation and virulence gene expression. The influence of LxA4 on antibiotic efficacy and the combined effects on biofilm formation were also investigated. LxA4 and RvD2 reduced P. aeruginosa biofilm formation and virulence gene expression. LxA4 increased ciprofloxacin inhibition on biofilm formation but did not affect ciprofloxacin's action on non-adherent bacteria. On the other hand, LxA4 increased bacterial killing action of imipenem but did not affect imipenem's action on biofilm. We also found that LxA4 can increase ciprofloxacin's bacterial killing ability in established biofilm. Together these results suggest that LxA4 has direct effects on P. aeruginosa biofilm formation and can increase antibiotic efficacy directly.

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a secondary analysis of the PITCHES trial.

OBJECTIVE: To evaluate whether a particular group of women with intrahepatic cholestasis of pregnancy (ICP), based on their presenting characteristics, would benefit from treatment with ursodeoxycholic acid (UDCA). DESIGN: Secondary analysis of the PITCHES trial (ISRCTN91918806). SETTING: United Kingdom. POPULATION OR SAMPLE: 527 women with ICP. METHODS: Subgroup analyses were performed to determine whether baseline bile acid concentrations or baseline itch scores moderated a woman's response to treatment with UDCA. MAIN OUTCOME MEASURES: Bile acid concentration and itch score. RESULTS: In women with baseline bile acid concentrations less than 40 µmol/l, treatment with UDCA resulted in increased post-randomisation bile acid concentrations (geometric mean ratio 1.19, 95% CI 1.00-1.41, P = 0.048). A test of interaction showed no significance (P = 0.647). A small, clinically insignificant difference was seen in itch response in women with a high baseline itch score (-6.0 mm, 95% CI -11.80 to -0.21, P = 0.042), with a test of interaction not showing significance (P = 0.640). Further subgroup analyses showed no significance. Across all women there was a weak relationship between bile acid concentrations and itch severity. CONCLUSIONS: There was no subgroup of women with ICP in whom a beneficial effect of treatment with UDCA on bile acid concentration or itch score could be identified. This confirms that its routine use in women with this condition for improvement of bile acid concentration or itch score should be reconsidered. TWEETABLE ABSTRACT: PITCHES: No group of women with ICP has been found in whom UDCA reduces bile acid concentrations or pruritus.

The impact of pre-eclampsia definitions on the identification of adverse outcome risk in hypertensive pregnancy - analyses from the CHIPS trial (Control of Hypertension in Pregnancy Study).

OBJECTIVE: To examine the association between pre-eclampsia definition and pregnancy outcome. DESIGN: Secondary analysis of Control of Hypertension in Pregnancy Study (CHIPS) trial data. SETTING: International multicentre randomised controlled trial (RCT). POPULATION: In all, 987 women with non-severe non-proteinuric pregnancy hypertension. METHODS: We evaluated the association between pre-eclampsia definitions and adverse pregnancy outcomes, stratified by hypertension type and blood pressure control. MAIN OUTCOME MEASURES: Main CHIPS trial outcomes: primary (perinatal loss or high-level neonatal care for >48 hours), secondary (serious maternal complications), birthweight <10th centile, severe maternal hypertension, delivery at <34 or <37 weeks, and maternal hospitalisation before birth. RESULTS: Of 979/987 women with informative data, 280 (28.6%) progressed to pre-eclampsia defined restrictively by new proteinuria, and 471 (48.1%) to pre-eclampsia defined broadly as proteinuria or one/more maternal symptoms, signs or abnormal laboratory tests. The broad (versus restrictive) definition had significantly higher sensitivities (range 62-79% versus 36-50%), lower specificities (range 53-65% versus 72-82%), and similar or higher diagnostic odds ratios and 'true-positive' to 'false-positive' ratios. Stratified analyses showed similar results. Addition of available fetoplacental manifestations (stillbirth or birthweight <10th centile) to the broad pre-eclampsia definition improved sensitivity (74-87%). CONCLUSIONS: A broad (versus restrictive) pre-eclampsia definition better identifies women who develop adverse pregnancy outcomes. These findings should be replicated in a prospective study within routine healthcare to ensure that the anticipated increase in surveillance and intervention in a larger number of women with pre-eclampsia is associated with improved outcomes, reasonable costs and congruence with women's values. TWEETABLE ABSTRACT: A broad (versus restrictive) pre-eclampsia definition better identifies the risk of adverse pregnancy outcomes.

Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett's Esophagus: A Phase 1 Pilot Study.

BACKGROUND: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. AIMS: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. METHODS: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. RESULTS: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1ß, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. CONCLUSIONS: When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.