Latent class analysis of health, social, and behavioral profiles associated with psychological distress among pregnant and postpartum women during the COVID-19 pandemic in the United States.

BACKGROUND: There is a growing body of literature documenting negative mental health impacts from the COVID-19 pandemic. The purpose of this study was to identify risk and protective factors associated with mental health and well-being among pregnant and postpartum women during the pandemic. METHODS: This was a cross-sectional, anonymous online survey study distributed to pregnant and postpartum (within 6 months) women identified through electronic health records from two large healthcare systems in the Northeastern and Midwestern United States. Survey questions explored perinatal and postpartum experiences related to the pandemic, including social support, coping, and health care needs and access. Latent class analysis was performed to identify classes among 13 distinct health, social, and behavioral variables. Outcomes of depression, anxiety, and stress were examined using propensity-weighted regression modeling. RESULTS: Fit indices demonstrated a three-class solution as the best fitting model. Respondents (N = 616) from both regions comprised three classes, which significantly differed on sleep- and exercise-related health, social behaviors, and mental health: Higher Psychological Distress (31.8%), Moderate Psychological Distress (49.8%), and Lower Psychological Distress (18.4%). The largest discriminatory issue was support from one's social network. Significant differences in depression, anxiety, and stress severity scores were observed across these three classes. Reported need for mental health services was greater than reported access. CONCLUSIONS: Mental health outcomes were largely predicted by the lack or presence of social support, which can inform public health decisions and measures to buffer the psychological impact of ongoing waves of the COVID-19 pandemic on pregnant and postpartum women. Targeted early intervention among those in higher distress categories may help improve maternal and child health.

Prevalence of Moral Injury, Burnout, Anxiety, and Depression in Healthcare Workers 2 Years in to the COVID-19 Pandemic.

ABSTRACT: COVID-19 has led to marked increases in healthcare worker distress. Studies of these phenomena are often limited to a particular element of distress or a specific subset of healthcare workers. We administered the Moral Injury Symptom Scale for Healthcare Professionals, Copenhagen Burnout Inventory, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 via online survey to 17,000 employees of a large academic medical center between December 2021 and February 2022. A total of 1945 participants completed the survey. Across all roles, the prevalence of moral injury, burnout, depression, and anxiety were 40.9%, 35.3%-60.6%, 25.4%, and 24.8%, respectively. Furthermore, 8.1% had been bothered by thoughts that they would be better off dead or of hurting themselves for "several days" or more frequently. Healthcare workers across all roles and practice settings are experiencing unsustainable levels of distress, with 1 in 12 regularly experiencing thoughts of self-harm.

Meningitis in the Guise of Dementia: Lyme-Induced Normal Pressure Hydrocephalus.

While the cause of altered mentation in the elderly may be multifactorial, infectious etiologies may be missed. This case report aims to detail an account of a patient with dementia, found to have Lyme meningitis in the setting of a normal pressure hydrocephalus (NPH). The patient smelled of urine and presented with ambulatory dysfunction, fitting the "wet, wacky, and wobbly" triad of NPH while also having subjective chills and leukocytosis. Non-contrast brain CT scan showed dilated ventricles. Cerebrospinal fluid (CSF) studies suggested aseptic meningitis. Serum studies using a modified two-tiered algorithm confirmed the diagnosis of Lyme disease. Treatment of the underlying condition with a prolonged course of doxycycline improved symptoms and clinical course. Review of the literature on the association between Lyme meningitis and NPH reveals that few cases of Lyme-related NPH have been reported worldwide and further research into the pathophysiology, diagnostic approach, treatment modalities, and management of NPH secondary to Lyme meningitis may be warranted.

COVID-19 Mitigation Among College Students: Social Influences, Behavioral Spillover, and Antibody Results.

By fall 2020, students returning to U.S. university campuses were mandated to engage in COVID-19 mitigation behaviors, including masking, which was a relatively novel prevention behavior in the U.S. Masking became a target of university mandates and campaigns, and it became politicized. Critical questions are whether the influences of injunctive norms and response efficacy on one behavior (i.e. masking) spill over to other mitigation behaviors (e.g. hand-washing), and how patterns of mitigation behaviors are associated with clinical outcomes. We conducted a cross-sectional survey of college students who returned to campus (N = 837) to explore these questions, and conducted COVID-19 antibody testing on a subset of participants to identify correlations between behaviors and disease burden. The results showed that college students were more likely to intend to wear face masks as they experienced more positive injunctive norms, liberal political views, stronger response efficacy for masks, and less pessimism. Latent class analysis revealed four mitigation classes: Adherents who intended to wear face masks and engage in the other COVID-19 mitigation behaviors; Hygiene Stewards and Masked Symptom Managers who intended to wear masks but only some other behaviors, and Refusers who intended to engage in no mitigation behaviors. Importantly, the Hygiene Stewards and Refusers had the highest likelihood of positive antibodies; these two classes differed in their masking intentions, but shared very low likelihoods of physical distancing from others and avoiding crowds or mass gatherings. The implications for theories of normative influences on novel behaviors, spillover effects, and future messaging are discussed.

Adoption and Discontinuance of Innovation Packages: A Longitudinal Study of Transitions in COVID-19 Mitigation.

The past decades have seen growing interest and application of interventions targeting the change of multiple behaviors at once. We advance this work by using the diffusion of innovations theory (DOI) to consider constellations of behaviors as innovation packages: multiple innovations that are logically related, interdependent in their use or effects, and often promoted as a set (Rogers, 2003). In addition, we embraced DOI's focus on behavioral decisions as a continual process that can include adoption and discontinuance over time, especially as new innovations (e.g., COVID-19 vaccine) appear. To that end, we conducted a latent transition analysis of COVID-19 mitigation behaviors (N = 697; 97% received a COVID-19 vaccine) across three time points in the pandemic: initial outbreak; a secondary, record-breaking rise in cases; and after the CDC recommended that fully vaccinated adults could discontinue wearing masks. This analysis allowed us to identify latent classes based on shared behavioral patterns and transitions between classes over time. The results showed evidence of three possible packages: (a) a package of traditional, symptom-management behaviors (covering coughs and sneezes, staying home if ill, and seeking medical care), (b) a package of just-novel COVID-19 behaviors (wearing masks, keeping six feet apart, and avoiding mass gatherings), and (c) a package of all COVID-19 mitigation behaviors. Movement between classes exemplified adoption and discontinuance of different packages, as well as widespread discontinuance with the replacement innovation: COVID-19 vaccines. Additional analyses showed that increases in hope were associated with sustained and delayed adoption; decreases in social approval were associated with discontinuance. Future directions in theorizing around innovation packages are discussed.

The potential of folate derivatives and Hantzsch esters to inhibit ultraviolet-induced reactive oxygen species.

Context: Ultraviolet (UV) radiation causes 60,000 premature deaths worldwide per year. In the US alone, UV-associated skin cancers cost over $8 billion annually. UV radiation causes harm primarily through inducing carcinogenic reactive oxygen species (ROS). Agents that reduce UV-induced ROS before carcinogenesis can occur are therefore highly desirable. Folate derivatives and Hantzsch esters have been shown to inhibit chemically-induced ROS, but have not been demonstrated to be effective at inhibiting UV-induced ROS. Objectives: (1) To evaluate in vitro inhibition of UV-induced ROS with a folate derivative. (2) To identify promising Hantzsch esters for further study by evaluating their energy favorability to inhibit some ROS through high precision quantum chemical methods (CBS-QB3, SMD solvent model, water). Study Design and Analysis: UACC 903 cells (Melanoma cell line) and fibroblast cells were cultured and marked with a fluorescent ROS dye. Cells were exposed to varying concentrations of a folate derivative, and ROS were induced by H2O2 or ultraviolet radiation. ROS inhibition was measured over time, and modeled on an S-shaped curve. High precision chemical methods (CBS-QB3, SMD solvent model, water) of elementary reaction steps involving the transfer of electrons (SET step), the transfer of hydrogen radicals and the transfer of hydride anions were used to evaluate the energy favorability of Hantzsch esters as ROS inhibitors and identify promising Hantzsch esters for future in vitro evaluation. Setting: In vitro analysis and quantum calculation. Intervention: Exposure to UV radiation. Outcome Measures: (1) ROS inhibition (2) Net energy of Hantzsch ester ROS interaction. Results: Folate derivatives inhibit ultraviolet radiation-induced ROS in melanoma and fibroblast cell lines in vitro. Several Hantzsch esters demonstrate energy favorability in inhibiting ROS in silico. Conclusions: Folate derivatives and their chemical analogs, Hantzsch esters, offer a method of inhibiting ROS induced by ultraviolet radiation, and hence, a potential method for reducing the tremendous health burden of ultraviolet radiation. Further study is needed to determine the extent to which this ROS inhibition decreased carcinogenesis.

Using artificial intelligence to support rapid, mixed-methods analysis: Developing an automated qualitative assistant (AQUA).

Context: Qualitative research - crucial for understanding human behavior - remains underutilized, in part due to the time and cost of annotating qualitative data (coding). Artificial intelligence (AI) has been suggested as a means to reduce those burdens. Older AI techniques (Latent Semantic Indexing / Latent Dirichlet Allocation (LSI/LDA)) have fallen short, in part because qualitative data is rife with idiom, non-standard expressions, and jargon. Objective: To develop an AI platform using updated techniques to augment qualitative data coding. Study Design and Analysis: We previously completed traditional qualitative analysis of a large dataset, with 11 qualitative categories and 72 subcategories (categories), and a final Cohen's kappa ≥ 0.65 as a measure of human inter-coder reliability (ICR) after coding. We built our Automated Qualitative Assistant (AQUA) using a semi-classical approach, replacing LSI/LDA with a graph-theoretic topic extraction and clustering method. AQUA was given the previously-identified qualitative categories and tasked with coding free-text data into those categories. Item coding was scored using cosine-similarity. Population Studied: Pennsylvanian adults. Instrument: Free-text responses to five open ended questions related to the COVID-19 pandemic (e.g. "What worries you most about the COVID-19 pandemic?"). Outcome Measures: AQUA's coding was compared to human coding using Cohen's kappa. This was done on all categories in aggregate, and also on category clusters to identify category groups amenable to AQUA support. AQUA's time to complete coding was compared to the time taken by the human coding team. Dataset: Five unlimited free-text survey answers from 538 responders. Results: AQUA's kappa for all categories was low (kappa~0.45), reflecting the challenge of automated analysis of diverse language. However, for several 3-category combinations (with less linguistic diversity), AQUA performed comparably to human coders, with an ICR kappa range of 0.62 to 0.72 based on test-train split. AQUA's analysis (including human interpretation) took approximately 5 hours, compared to approximately 30 person hours for traditional coding. Conclusions: AQUA enables qualitative researchers to identify categories amenable to automated coding, and to rapidly conduct that coding on the entirety of very large datasets. This saves time and money, and avoids limitations inherent in limiting qualitative analysis to limited samples of a given dataset.

External Validation of the COVID-NoLab and COVID-SimpleLab Prognostic Tools.

Our objective was to externally validate 2 simple risk scores for mortality among a mostly inpatient population with COVID-19 in Canada (588 patients for COVID-NoLab and 479 patients for COVID-SimpleLab). The mortality rates in the low-, moderate-, and high-risk groups for COVID-NoLab were 1.1%, 9.6%, and 21.2%, respectively. The mortality rates for COVID-SimpleLab were 0.0%, 9.8%, and 20.0%, respectively. These values were similar to those in the original derivation cohort. The 2 simple risk scores, now successfully externally validated, offer clinicians a reliable way to quickly identify low-risk inpatients who could potentially be managed as outpatients in the event of a bed shortage. Both are available online (https://ebell-projects.shinyapps.io/covid_nolab/ and https://ebell-projects.shinyapps.io/COVID-SimpleLab/).

Perceptions and knowledge regarding the COVID-19 pandemic between U.S. and China: a mixed methods study.

BACKGROUND: SARS-CoV-2, a new coronavirus first reported by China on December 31st, 2019, has led to a global health crisis that continues to challenge governments and public health organizations. Understanding COVID-19 knowledge, attitudes, and practices (KAP) is key for informing messaging strategies to contain the pandemic. Cross-national studies (e.g.: comparing China to the U.S.) are needed to better understand how trans-cultural differences may drive differences in pandemic response and behaviors. The goal of the study is to compare knowledge and perceptions of COVID-19 between adults in China and the U.S. These data will provide insight into challenges these nations may face in coordinating pandemic response. METHODS: This is a convergent mixed methods study comparing responses from China and the U.S. to a multinational COVID-19 KAP online survey. The survey included five quantitative constructs and five open-ended questions. Chinese respondents (n = 56) were matched for gender, age, education, perceived social standing, and time of survey completion with a U.S. cohort (n = 57) drawn from 10,620 U.S. RESPONDENTS: Quantitative responses were compared using T-test & Fisher-Exact tests. Inductive thematic analysis was applied to open-ended questions. RESULTS: Both U.S. and Chinese samples had relatively high intention to follow preventive behaviors overall. Differences in intended compliance with a specific recommendation appear to be driven by the different cultural norms in U.S. and China. Both groups expressed trepidation about the speed of COVID-19 vaccine development, driven by concern for safety among Chinese respondents, and concern for efficacy among U.S. RESPONDENTS: The Chinese cohort expressed worries about other countries' passive handling of the pandemic while the U.S. cohort focused on domestic responses from individuals and government. U.S. participants appeared more knowledgeable on some aspects of COVID-19. Different perspectives regarding COVID-19 origins were identified among the two groups. Participants from both samples reported high trust in health professionals and international health organizations. CONCLUSIONS: Mixed methods data from this cross-national analysis suggests sociocultural differences likely influence perceptions and knowledge of COVID-19 and its related public health policies. Discovering and addressing these culturally-based differences and perceptions are essential to coordinate a global pandemic response.

Skeptical Health Mavens May Limit COVID-19 Vaccine Diffusion: Using the Innovation Diffusion Cycle to Interpret Results of a Cross-sectional Survey among People Who are Socially Vulnerable.

We sought to identify barriers to COVID-19 vaccine uptake among persons who are socially vulnerable in light of the natural cycle of innovation diffusion. Widespread adoption of a health innovation requires a cadre of opinion leaders to build on successes experienced by early adopters. One type of opinion leader in healthcare are health mavens: members of a community who maintain up-to-date health knowledge and share their knowledge others. We surveyed 139 persons who are socially vulnerable regarding their COVID-19 vaccination intention, and evaluated their responses based on psychological traits captured by two scales: innovativeness and health mavenism. Health mavenism was not strongly correlated with COVID-19 vaccine intention. Health mavens often relied on their own healthcare providers (n = 46) and health agency websites (n = 42) for vaccine information. Those who relied on their faith leaders (n = 4) reported a lower likelihood of getting vaccinated (31.5% vs. 76.0%, p < .05). The observed lack of support by health mavens represents a critical barrier to COVID-19 vaccine uptake; targeting campaigns to health mavens may increase COVID-19 vaccine uptake in socially vulnerable communities.

Extending the Theory of Normative Social Behavior: Collective Norms, Opinion Leadership, and Masking During the COVID-19 Pandemic.

Novel, public behaviors, such as masking, should be susceptible to normative influence. This paper advances the theory of normative social behavior by considering a new set of moderators of normative influence - superdiffuser traits - and by clarifying the antecedents and consequences of exposure to collective norms. We use data from a two-wave survey of a cohort living in one U.S. county during the pandemic (N = 913) to assess normative effects on masking. We also used a bipartite network (based on people shopping for food in the same stores) to examine exposure to collective norms. The results show different superdiffuser traits have distinct effects on the relationship between perceived injunctive norms and masking intentions. Exposure to collective norms influences masking, but this influence depends on how people interact with their social environments. Network analysis shows that behavioral homophily is a significant predictor of selective exposure to collective norms earlier (but not later) in the pandemic. Implications for understanding normative influence in a context where opinion leadership matters are discussed.

Risks of Severe COVID-19 Outcomes Among Patients With Diabetic Polyneuropathy in the United States.

CONTEXT: Diabetic neuropathy (DN) affects more than 50% of diabetic patients who are also likely to have compromised immune system and respiratory function, both of which can make them susceptible to the SARS-CoV-2 virus. OBJECTIVE: To assess the risk of severe COVID-19 illness among adults with DN, compared with those with no DN and those with no diabetes. SETTING: The analysis utilized electronic health records from 55 US health care organizations in the TriNetX research database. DESIGN: A retrospective cohort study. PARTICIPANTS: The analysis included 882 650 adults diagnosed with COVID-19 in January 2020 to June 2021, including 16 641 with DN, 81 329 with diabetes with no neuropathy, and 784 680 with no diabetes. OUTCOME MEASURES: The presence of health care utilization (admissions to emergency department, hospital, intensive care unit), 30-day mortality, clinical presentation (cough, fever, hypoxemia, dyspnea, or acute respiratory distress syndrome), and diagnostic test results after being infected affected by COVID-19. RESULTS: The DN cohort was 1.19 to 2.47 times more likely than the non-DN cohorts to utilize care resources, receive critical care, and have higher 30-day mortality rates. Patients with DN also showed increased risk (1.13-2.18 times) of severe symptoms, such as hypoxemia, dyspnea, and acute respiratory distress syndrome. CONCLUSIONS: Patients with DN had a significantly greater risk of developing severe COVID-19-related complications than those with no DN. It is critical for the public health community to continue preventive measures, such as social distancing, wearing masks, and vaccination, to reduce infection rates, particularly in higher risk groups, such as those with DN.

Adjunctive osteopathic therapy for hospitalized COVID-19 patients: A feasibility-oriented chart review study with matched controls.

Background: Osteopathic manipulative treatment (OMT) may improve outcomes during COVID-related respiratory distress - the most common cause of death from novel coronavirus (SARS-CoV-2). Outcomes from OMT treatments of respiratory distress during the COVID-19 pandemic have not been reported. Objective: Assess adjunctive OMT in hospitalized patients with SARS-CoV-2 and respiratory distress. Design: Feasibility oriented retrospective observational cohort study. Setting: COVID-19 (non-ICU) ward in a tertiary academic medical center. Methods: Inpatients received daily OMT treatments of rib raising, abdominal diaphragm doming, thoracic pump and pedal pump. Primary outcomes were procedural acceptance, satisfaction, side effects, and adverse events. Secondary outcomes were patient-reported clinical change after therapy; number of hospital days; need during hospitalization for high-flow oxygen, C-PAP/BiPAP or intensive care; need for supplementary oxygen at discharge; and discharge disposition. Participants: Hospitalized adults with SARS-CoV-2 infection and respiratory distress. Results: OMT (n = 27) and Control (n = 152) groups were similar in demographics and most laboratory studies. 90% of patients accepted OMT and reported high satisfaction (4.26/±0.71 (maximum 5)), few negative effects, no adverse events, and positive clinical change (5.07 ± 0.96 (maximum 7)). Although no significant differences were found in secondary outcomes, OMT patients trended towards fewer hospital days than Controls (p = 0.053; Cohen's d = 0.22), a relationship that trended towards correlation with number of co-morbidities (p = 0.068). Conclusion: Hospitalized patients with respiratory distress and COVID-19 reported acceptance, satisfaction, and greater ease of breathing after a four-part OMT protocol, and appear to have a shorter length of hospitalization. Randomized controlled trials are needed to confirm these results.

Knowledge, Perceptions, and Preferred Information Sources Related to COVID-19 Among Central Pennsylvania Adults Early in the Pandemic: A Mixed Methods Cross-Sectional Survey.

PURPOSE: To explore public knowledge, understanding of public health recommendations, perceptions, and trust in information sources related to COVID-19. METHODS: A cross-sectional survey of central Pennsylvanian adults evaluated self-reported knowledge, and a convergent, mixed methods design was used to assess beliefs about recommendations, intended behaviors, perceptions, and concerns related to infectious disease risk, and trust of information sources. RESULTS: The survey was completed by 5,948 adults. The estimated probability of correct response for the basic knowledge score, weighted with confidence, was 0.79 (95% CI, 0.79-0.80). Knowledge was significantly higher in patients with higher education and nonminority race. While the majority of respondents reported that they believed following CDC recommendations would decrease the spread of COVID-19 in their community and intended to adhere to them, only 65.2% rated social isolation with the highest level of belief and adherence. The most trusted information source was federal public health websites (42.8%). Qualitative responses aligned with quantitative data and described concerns about illness, epidemiologic issues, economic and societal disruptions, and distrust of the executive branch's messaging. The survey was limited by a lack of minority representation, potential selection bias, and evolving COVID-19 information that may impact generalizability and interpretability. CONCLUSIONS: Knowledge about COVID-19 and intended adherence to behavioral recommendations were high. There was substantial distrust of the executive branch of the federal government, however, and concern about mixed messaging and information overload. These findings highlight the importance of consistent messaging from trusted sources that reaches diverse groups.

Physician moral injury in the context of moral, ethical and legal codes.

After 40 years of attributing high rates of physician career dissatisfaction, attrition, alcoholism, divorce and suicide to 'burnout', there is growing recognition that these outcomes may instead be caused by moral injury. This has led to a debate about the relative diagnostic merits of these two terms, a recognition that interventions designed to treat burnout may be ineffective, and much perplexity about how-if at all-this changes anything.The current research seeks to develop the construct of moral injury outside military contexts, generate more robust validity tests and more fully describe and measure the experiences of persons exposed to moral harms. Absent from the literature is a mechanism through which to move from the collective moral injury experience of physicians to a systematic change in the structure of medical practice. To address this, after providing a brief history, definitions and contrasts between burnout, moral distress and moral injury, we review the interplay of moral and ethical codes in the context of moral injury. We conclude by suggesting that professional associations can potentially prevent moral injury by providing protections for physicians within their codes of ethics.

Exploring Behavioral Typologies to Inform COVID-19 Health Campaigns: A Person-Centered Approach.

As the United States continues to be ravaged by COVID-19, it becomes increasingly important to implement effective public health campaigns to improve personal behaviors that help control the spread of the virus. To design effective campaigns, research is needed to understand the current mitigation intentions of the general public, diversity in those intentions, and theoretical predictors of them. COVID-19 campaigns will be particularly challenging because mitigation involves myriad, diverse behaviors. This study takes a person-centered approach to investigate data from a survey (N = 976) of Pennsylvania adults. Latent class analysis revealed five classes of mitigation: one marked by complete adherence with health recommendations (34% of the sample), one by complete refusal (9% of the sample), and three by a mixture of adherence and refusal. Statistically significant covariates of class membership included relatively positive injunctive norms, risk due to essential workers in the household, personal knowledge of someone who became infected with COVID-19, and belief that COVID-19 was a leaked biological weapon. Additionally, trait reactance was associated with non-adherence while health mavenism was associated with adherence. These findings may be used to good effect by local healthcare providers and institutions, and also inform broader policy-making decisions regarding public health campaigns to mitigate COVID-19.

Lower Intent to Comply with COVID-19 Public Health Recommendations Correlates to Higher Disease Burden in Following 30 Days.

OBJECTIVES: We sought to determine whether self-reported intent to comply with public health recommendations correlates with future coronavirus disease 2019 (COVID-19) disease burden. METHODS: A cross-sectional, online survey of US adults, recruited by snowball sampling, from April 9 to July 12, 2020. Primary measurements were participant survey responses about their intent to comply with public health recommendations. Each participant's intent to comply was compared with his or her local COVID-19 case trajectory, measured as the 7-day rolling median percentage change in COVID-19 confirmed cases within participants' 3-digit ZIP code area, using public county-level data, 30 days after participants completed the survey. RESULTS: After applying raking techniques, the 10,650-participant sample was representative of US adults with respect to age, sex, race, and ethnicity. Intent to comply varied significantly by state and sex. Lower reported intent to comply was associated with higher COVID-19 case increases during the following 30 days. For every 3% increase in intent to comply with public health recommendations, which could be achieved by improving average compliance by a single point for a single item, we estimate a 9% reduction in new COVID-19 cases during the subsequent 30 days. CONCLUSIONS: Self-reported intent to comply with public health recommendations may be used to predict COVID-19 disease burden. Measuring compliance intention offers an inexpensive, readily available method of predicting disease burden that can also identify populations most in need of public health education aimed at behavior change.

Increasing system-wide implementation of opioid prescribing guidelines in primary care: findings from a non-randomized stepped-wedge quality improvement project.

BACKGROUND: Clinician utilization of practice guidelines can reduce inappropriate opioid prescribing and harm in chronic non-cancer pain; yet, implementation of "opioid guidelines" is subpar. We hypothesized that a multi-component quality improvement (QI) augmentation of "routine" system-level implementation efforts would increase clinician adherence to the opioid guideline-driven policy recommendations. METHODS: Opioid policy was implemented system-wide in 26 primary care clinics. A convenience sample of 9 clinics received the QI augmentation (one-hour academic detailing; 2 online educational modules; 4-6 monthly one-hour practice facilitation sessions) in this non-randomized stepped-wedge QI project. The QI participants were volunteer clinic staff. The target patient population was adults with chronic non-cancer pain treated with long-term opioids. The outcomes included the clinic-level percentage of target patients with a current treatment agreement (primary outcome), rates of opioid-benzodiazepine co-prescribing, urine drug testing, depression and opioid misuse risk screening, and prescription drug monitoring database check; additional measures included daily morphine-equivalent dose (MED), and the percentages of all target patients and patients prescribed ≥90 mg/day MED. T-test, mixed-regression and stepped-wedge-based analyses evaluated the QI impact, with significance and effect size assessed with two-tailed p < 0.05, 95% confidence intervals and/or Cohen's d. RESULTS: Two-hundred-fifteen QI participants, a subset of clinical staff, received at least one QI component; 1255 patients in the QI and 1632 patients in the 17 comparison clinics were prescribed long-term opioids. At baseline, more QI than comparison clinic patients were screened for depression (8.1% vs 1.1%, p = 0.019) and prescribed ≥90 mg/day MED (23.0% vs 15.5%, p = 0.038). The stepped-wedge analysis did not show statistically significant changes in outcomes in the QI clinics, when accounting for the comparison clinics' trends. The Cohen's d values favored the QI clinics in all outcomes except opioid-benzodiazepine co-prescribing. Subgroup analysis showed that patients prescribed ≥90 mg/day MED in the QI compared to comparison clinics improved urine drug screening rates (38.8% vs 19.1%, p = 0.02), but not other outcomes (p ≥ 0.05). CONCLUSIONS: Augmenting routine policy implementation with targeted QI intervention, delivered to volunteer clinic staff, did not additionally improve clinic-level, opioid guideline-concordant care metrics. However, the observed effect sizes suggested this approach may be effective, especially in higher-risk patients, if broadly implemented. TRIAL REGISTRATION: Not applicable.

Managing Hypertension Using Combination Therapy.

More than 70% of adults treated for primary hypertension will eventually require at least two antihypertensive agents, either initially as combination therapy or as add-on therapy if monotherapy and lifestyle modifications do not achieve adequate blood pressure control. Four main classes of medications are used in combination therapy for the treatment of hypertension: thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). ACEIs and ARBs should not be used simultaneously. In black patients, at least one agent should be a thiazide diuretic or a calcium channel blocker. Patients with heart failure with reduced ejection fraction should be treated initially with a beta blocker and an ACEI or ARB (or an angiotensin receptor-neprilysin inhibitor), followed by add-on therapy with a mineralocorticoid receptor antagonist and a diuretic based on volume status. Treatment for patients with chronic kidney disease and proteinuria should include an ACEI or ARB plus a thiazide diuretic or a calcium channel blocker. Patients with diabetes mellitus should be treated similarly to those without diabetes unless proteinuria is present, in which case combination therapy should include an ACEI or ARB.