Adjusting Incidence Estimates with Laboratory Test Performances: A Pragmatic Maximum Likelihood Estimation-Based Approach.

Understanding the incidence of disease is often crucial for public policy decision-making, as observed during the COVID-19 pandemic. Estimating incidence is challenging, however, when the definition of incidence relies on tests that imperfectly measure disease, as in the case when assays with variable performance are used to detect the SARS-CoV-2 virus. To our knowledge, there are no pragmatic methods to address the bias introduced by the performance of labs in testing for the virus. In the setting of a longitudinal study, we developed a maximum likelihood estimation-based approach to estimate laboratory performance-adjusted incidence using the expectation-maximization algorithm. We constructed confidence intervals (CIs) using both bootstrapped-based and large-sample interval estimator approaches. We evaluated our methods through extensive simulation and applied them to a real-world study (TrackCOVID), where the primary goal was to determine the incidence of and risk factors for SARS-CoV-2 infection in the San Francisco Bay Area from July 2020 to March 2021. Our simulations demonstrated that our method converged rapidly with accurate estimates under a variety of scenarios. Bootstrapped-based CIs were comparable to the large-sample estimator CIs with a reasonable number of incident cases, shown via a simulation scenario based on the real TrackCOVID study. In more extreme simulated scenarios, the coverage of large-sample interval estimation outperformed the bootstrapped-based approach. Results from the application to the TrackCOVID study suggested that assuming perfect laboratory test performance can lead to an inaccurate inference of the incidence. Our flexible, pragmatic method can be extended to a variety of disease and study settings.

Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2.

Long COVID (LC) occurs after at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, yet its etiology remains poorly understood. We used 'omic" assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. We found that LC individuals exhibited systemic inflammation and immune dysregulation. This was evidenced by global differences in T cell subset distribution implying ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. LC individuals displayed increased frequencies of CD4+ T cells poised to migrate to inflamed tissues and exhausted SARS-CoV-2-specific CD8+ T cells, higher levels of SARS-CoV-2 antibodies and a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Our analysis suggested an improper crosstalk between the cellular and humoral adaptive immunity in LC, which can lead to immune dysregulation, inflammation and clinical symptoms associated with this debilitating condition.

Innovation in public delivery systems: How one safety net hospital implemented new heart monitoring technology.

This case study examines how a public delivery system hospital implemented a heart monitoring patch in place of existing electrocardiogram (ECG) monitoring by pursuing a holistic value proposition. For example, leaders identified opportunity costs embedded in the existing ECG monitoring staffing. Stakeholders also rallied around values such as patient safety, patient experience, and quality of care. Implementation also benefited from external philanthropic and industry partnerships, which facilitated a pilot period to implement new workflows, demonstrate proof-of-concept, and evaluate process improvements. Despite implementation success, ongoing procurement and reimbursement challenges demonstrate the messiness of innovation, even after reaching a "maintenance" phase. Availability of patient-facing material in multiple languages is one example of an implementation gap in safety net settings. New policies by health systems, payers, and others are needed to establish pathways for future high-value innovations.

Pulmonary Specialist-Supported Health Coaching Delivered by Lay Personnel Improves Receipt of Quality Care for Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

Purpose: Half of people living with chronic obstructive pulmonary disease (COPD) do not receive high-quality, evidenced-based care as described in international guidelines. We conducted secondary data analysis of a previously published study to assess the ability of a model of lay health coaching to improve provision of guideline-based care in a primary care setting. Methods: As part of a randomized controlled trial, we recruited English- and Spanish-speaking patients with moderate to severe COPD from primary care clinics serving a low-income, predominantly African American population. Participants were randomized to receive usual care or 9 months of health coaching from primary care personnel informed by a pulmonary specialist practitioner. Outcome measures included prescription of appropriate inhaler therapy, participation in COPD-related education, engagement with specialty care, prescription of smoking cessation medications, and patient ratings of the quality of care. Results: Baseline quality measures did not differ between study arms. At 9 months, coached patients were more likely (increase of 9.3% over usual care; P=0.014) to have received guideline-based inhalers compared to those in usual care. Coached patients were more likely to engage with pulmonary specialty care (increase of 8.3% over usual care with at least 1 visit; P=0.04) and educational classes (increase of 5.3% over usual care; P=0.03). Receipt of smoking cessation medications among patients smoking at baseline in the health coaching group increased 21.1 percentage points more than in usual care, a difference near statistical significance (P=0.06). Conclusions: Health coaching may improve the provision of quality chronic illness care for conditions such as COPD.

Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection.

BACKGROUND: Persistent symptoms among some persons who develop COVID-19 has led to the hypothesis that SARS-CoV-2 may, in some form or location, persist for long periods following acute infection. Several studies have shown data in this regard but are limited by non-representative and small study populations, short duration since acute infection, and lack of a true-negative comparator group to assess assay specificity. METHODS: We evaluated adults with RNA-confirmed COVID-19 at multiple time points following acute infection (pandemic-era participants) and adults with specimens collected prior to 2020 (pre-pandemic era). Using once-thawed plasma, we employed the Simoa® (Quanterix) single molecule array detection platform to measure SARS-CoV-2 spike, S1, and nucleocapsid antigens. RESULTS: Compared to 250 pre-pandemic participants who had 2% assay positivity, detection of any SARS-CoV-2 antigen was significantly more frequent among 171 pandemic-era participants at three different time periods in the post-acute phase of infection. The absolute difference in SARS-CoV-2 plasma antigen prevalence was +11% (95% CI: +5.0% to +16%) at 3.0-6.0 months post-onset of COVID-19; +8.7% (95% CI: +3.1% to +14%) at 6.1 to 10.0 months; and +5.4% (95% CI: +0.42% to +10%) at 10.1-14.1 months. Hospitalization for acute COVID-19 and, among the non-hospitalized, worse self-reported health during acute COVID-19 were associated with greater post-acute phase antigen detection. CONCLUSIONS: Compared to uninfected persons, there is an excess prevalence of SARS-CoV-2 antigenemia in SARS-CoV-2-infected individuals up to 14 months after acute COVID-19. These findings motivate an urgent research agenda regarding the short-term and long-term clinical manifestations of this viral persistence.

Association of protective behaviors with SARS-CoV-2 infection: results from a longitudinal cohort study of adults in the San Francisco Bay Area.

PURPOSE: In an effort to decrease transmission during the first years of the COVID-19 pandemic, public health officials encouraged masking, social distancing, and working from home, and restricted travel. However, many studies of the effectiveness of these measures had significant methodologic limitations. In this analysis, we used data from the TrackCOVID study, a longitudinal cohort study of a population-based sample of 3846 adults in the San Francisco Bay Area, to evaluate the association between self-reported protective behaviors and incidence of SARS-CoV-2 infection. METHODS: Participants without SARS-CoV2 infection were enrolled from August to December 2020 and followed monthly with testing and surveys (median of four visits). RESULTS: A total of 118 incident infections occurred (3.0% of participants). At baseline, 80.0% reported always wearing a mask; 56.0% avoided contact with nonhousehold members some/most of the time; 9.6% traveled outside the state; and 16.0% worked 20 or more hours per week outside the home. Factors associated with incident infection included being Black or Latinx, having less than a college education, and having more household residents. The only behavioral factor associated with incident infection was working outside the home (adjusted hazard ratio 1.62, 95% confidence interval 1.02-2.59). CONCLUSIONS: Focusing on protecting people who cannot work from home could help prevent infections during future waves of COVID-19, or future pandemics from respiratory viruses. This focus must be balanced with the known importance of directing resources toward those at risk of severe infections.

Autoantigen profiling reveals a shared post-COVID signature in fully recovered and long COVID patients.

Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as long COVID. The underlying pathophysiology of long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of SARS-CoV-2 infection and certain other post-COVID sequelae, their potential role in long COVID is important to investigate. Here, we apply a well-established, unbiased, proteome-wide autoantibody detection technology (T7 phage-display assay with immunoprecipitation and next-generation sequencing, PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected that separated individuals with prior SARS-CoV-2 infection from those never exposed to SARS-CoV-2, we did not detect patterns of autoreactivity that separated individuals with long COVID from individuals fully recovered from COVID-19. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and long COVID was apparent by this assay.

Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2.

Long COVID (LC), a type of post-acute sequelae of SARS-CoV-2 infection (PASC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple "omics" assays (CyTOF, RNAseq/scRNAseq, Olink) and serology to deeply characterize both global and SARS-CoV-2-specific immunity from blood of individuals with clear LC and non-LC clinical trajectories, 8 months following infection and prior to receipt of any SARS-CoV-2 vaccine. Our analysis focused on deep phenotyping of T cells, which play important roles in immunity against SARS-CoV-2 yet may also contribute to COVID-19 pathogenesis. Our findings demonstrate that individuals with LC exhibit systemic inflammation and immune dysregulation. This is evidenced by global differences in T cell subset distribution in ways that imply ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. Individuals with LC harbored increased frequencies of CD4+ T cells poised to migrate to inflamed tissues, and exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and in contrast to non-LC individuals, exhibited a mis-coordination between their SARS-CoV-2-specific T and B cell responses. RNAseq/scRNAseq and Olink analyses similarly revealed immune dysregulatory mechanisms, along with non-immune associated perturbations, in individuals with LC. Collectively, our data suggest that proper crosstalk between the humoral and cellular arms of adaptive immunity has broken down in LC, and that this, perhaps in the context of persistent virus, leads to the immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition.

Autoantigen profiling reveals a shared post-COVID signature in fully recovered and Long COVID patients.

Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as Long COVID. The underlying pathophysiology of Long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of COVID infection and certain other post-COVID sequelae, their potential role in Long COVID is important to investigate. Here we apply a well-established, unbiased, proteome-wide autoantibody detection technology (PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with Long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected which separates individuals with prior COVID infection from those never exposed to COVID, we did not detect patterns of autoreactivity that separate individuals with Long COVID relative to individuals fully recovered from SARS-CoV-2 infection. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and Long COVID was apparent by this assay.

Incidence and Prevalence of Coronavirus Disease 2019 Within a Healthcare Worker Cohort During the First Year of the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic.

BACKGROUND: Preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2_ infections in healthcare workers (HCWs) is critical for healthcare delivery. We aimed to estimate and characterize the prevalence and incidence of coronavirus disease 2019 (COVID-19) in a US HCW cohort and to identify risk factors associated with infection. METHODS: We conducted a longitudinal cohort study of HCWs at 3 Bay Area medical centers using serial surveys and SARS-CoV-2 viral and orthogonal serological testing, including measurement of neutralizing antibodies. We estimated baseline prevalence and cumulative incidence of COVID-19. We performed multivariable Cox proportional hazards models to estimate associations of baseline factors with incident infections and evaluated the impact of time-varying exposures on time to COVID-19 using marginal structural models. RESULTS: A total of 2435 HCWs contributed 768 person-years of follow-up time. We identified 21 of 2435 individuals with prevalent infection, resulting in a baseline prevalence of 0.86% (95% confidence interval [CI], .53%-1.32%). We identified 70 of 2414 incident infections (2.9%), yielding a cumulative incidence rate of 9.11 cases per 100 person-years (95% CI, 7.11-11.52). Community contact with a known COVID-19 case was most strongly correlated with increased hazard for infection (hazard ratio, 8.1 [95% CI, 3.8-17.5]). High-risk work-related exposures (ie, breach in protective measures) drove an association between work exposure and infection (hazard ratio, 2.5 [95% CI, 1.3-4.8). More cases were identified in HCWs when community case rates were high. CONCLUSIONS: We observed modest COVID-19 incidence despite consistent exposure at work. Community contact was strongly associated with infections, but contact at work was not unless accompanied by high-risk exposure.

Race-ethnicity and COVID-19 Vaccination Beliefs and Intentions: A Cross-Sectional Study among the General Population in the San Francisco Bay Area.

OBJECTIVE: The study was designed to compare intentions to receive COVID-19 vaccination by race-ethnicity, to identify beliefs that may mediate the association between race-ethnicity and intention to receive the vaccine and to identify the demographic factors and beliefs most strongly predictive of intention to receive a vaccine. DESIGN: Cross-sectional survey conducted from November 2020 to January 2021, nested within a longitudinal cohort study of the prevalence and incidence of SARS-CoV-2 among a general population-based sample of adults in six San Francisco Bay Area counties (called TrackCOVID). Study Cohort: In total, 3161 participants among the 3935 in the TrackCOVID parent cohort responded. RESULTS: Rates of high vaccine willingness were significantly lower among Black (41%), Latinx (55%), Asian (58%), Multi-racial (59%), and Other race (58%) respondents than among White respondents (72%). Black, Latinx, and Asian respondents were significantly more likely than White respondents to endorse lack of trust of government and health agencies as a reason not to get vaccinated. Participants' motivations and concerns about COVID-19 vaccination only partially explained racial-ethnic differences in vaccination willingness. Concerns about a rushed government vaccine approval process and potential bad reactions to the vaccine were the two most important factors predicting vaccination intention. CONCLUSIONS: Vaccine outreach campaigns must ensure that the disproportionate toll of COVID-19 on historically marginalized racial-ethnic communities is not compounded by inequities in vaccination. Efforts must emphasize messages that speak to the motivations and concerns of groups suffering most from health inequities to earn their trust to support informed decision making.

Implementation and Impact of the Pulmonary Specialist Health Coach Consultation Model to Improve Care for Patients with COPD.

BACKGROUND: Health coaching has emerged as an important tool for improving patient-centered care in primary care practice but has not specifically been evaluated for patients whose care is shared by a primary care provider (PCP) and specialist. METHODS: As part of a nine-month randomized controlled trial comparing health coaching to usual care for patients with chronic obstructive pulmonary disease (COPD), the authors developed the Pulmonary Specialist Health Coach Consultation (PuSHCon). In this novel model, health coaches facilitated pulmonary specialist consultations for patients with COPD without the need for an in-person visit. Observational data from the randomized controlled trial were analyzed to study the implementation, adoption, and impact of the PuSHCon model for 70 of 92 patients randomized to the health coaching arm and for 17 of 100 patients in the control arm (who received PuSHCon after the end of the study). Quality of care was measured using the Patient Assessment of Chronic Illness Care (PACIC). RESULTS: Of 87 patients who participated in PuSHCon, 74 (85.1%) received one or more specialist recommendations, of which 86.8% were implemented. Only 12 patients (13.8%) subsequently required an in-person visit with the PuSHCon specialist. The proportion of PuSHCon participants receiving guideline-concordant care increased from 64.7% to 94.1% (p < 0.001). The mean PACIC item score increased from 3.48 to 3.74 (p = 0.03). CONCLUSION: The PuSHCon model facilitated consultations that resulted in changes in care, which were implemented for a majority of patients. Guideline-concordant care and patient-reported quality of care increased over nine months. This model could potentially be expanded to help patients with other chronic conditions when PCPs and specialists share patient care.

Patient and caregiver factors in ambulatory incident reports: a mixed-methods analysis.

OBJECTIVES: Patients and caregivers are the primary stakeholders in ambulatory safety, given they perform daily chronic disease self-management, medication administration and outpatient follow-up. However, little attention has been given to their role in adverse events. We identified themes related to patient and caregiver factors and challenges in ambulatory safety incident reports from a Patient Safety Organization. METHODS: We conducted a mixed-methods analysis of ambulatory incident reports submitted to the Collaborative Healthcare Patient Safety Organization, including 450 hospitals or clinic members in 13 US states. We included events that had patient and/or caregiver behavioural, socioeconomic and clinical factors that may have contributed to the event. Two members of the team independently coded patient/caregiver factors, with dual coding of 20% of events. We then conducted a 'frequent item set' analysis to identify which factors most frequently co-occurred. We applied inductive analysis to the most frequent sets to interpret themes. Our team included a diverse stakeholder advisory council of patients, caregivers and healthcare staff. RESULTS: We analysed 522 incident reports and excluded 73 for a final sample of 449 events. Our co-occurrence analysis found the following three themes: (1) clinical advice may conflict with patient priorities; (2) breakdowns in communication and patient education cause medication adverse events and (3) patients with disabilities are vulnerable to the external environment. CONCLUSIONS: Ambulatory safety reports capture both structural and behavioural factors contributing to adverse events. Actionable takeaways include the following: improving clinician counselling of patients to convey medical advice to elicit priorities, enhanced education regarding medication adverse events and expanding safety precautions for patients with disabilities at home. Ambulatory safety reporting must include patients in reporting and event review for better mitigation of future harm.

Primary Care Clinician Burnout and Engagement Association With Clinical Quality and Patient Experience.

BACKGROUND: Burnout and engagement are commonly conceptualized as opposite ends of a spectrum, and there is concern that high clinician burnout and lack of engagement may adversely impact patient care. METHODS: We matched self-reported data on burnout and engagement for 182 primary care clinicians with data on clinical quality (cancer screenings, hypertension and diabetes control) and patient experience (Clinician and Group Survey-Consumer Assessment of Healthcare Providers and Systems [CG-CAHPS] communication scores, overall rating, and likelihood to recommend the clinic). Multivariable linear regression models examined burnout, engagement, or burnout-engagement phenotype (eg, high burnout-low engagement) as predictors of quality and patient experience. RESULTS: One-third of clinicians in this sample did not fall along the spectrum of low burnout-high engagement to high burnout-low engagement. Neither burnout nor engagement on their own was associated with quality or patient experience measures. However, clinicians with high burnout who also were highly engaged had the highest average ratings for all 3 patient experience domains: clinician communication, overall rating of the clinician, and overall rating of the clinic. DISCUSSION: The results of our study challenge the assumptions that burnout and engagement are opposite ends of a spectrum and that burnout or low engagement adversely impact quality of care and patient experience. Greater understanding is needed of how best to support dedicated clinicians who may provide quality care at the expense of their personal well-being.

"She Showed Me How to Help Myself": A Qualitative Study of Health Coaching for Management of Chronic Obstructive Pulmonary Disease.

OBJECTIVE: To explore attitudes and beliefs about the role of health coaching for vulnerable populations, including people experiencing substance use or homelessness. METHODS: From May-July 2016, we conducted semi-structured qualitative interviews with patients, primary care clinicians, pulmonary specialists, and health coaches participating in a study of health coaching for chronic obstructive pulmonary disease (COPD). We developed a codebook and applied it in Atlas.ti, generating themes for frequently occurring codes. RESULTS: All stakeholder groups (n=20 patients, 11 primary care clinicians, three specialists, and two health coaches), reported improved COPD management and behavior change, even for patients experiencing substance use or homelessness. Clinicians observed greater symptom awareness and prioritization of COPD during the medical visit. The strength of the health coaching relationship and flexibility of the role were key to its effectiveness. CONCLUSION: Lay health coaching may provide a model to meet the needs of highly vulnerable populations with COPD.

Pilot of Brief Health Coaching Intervention to Improve Adherence to Positive Airway Pressure Therapy.

BACKGROUND: Adherence to positive airway pressure (PAP) therapies is poor, particularly among low-income populations and racial minorities. This study tested a low-resource, brief telephonic health coaching intervention to improve PAP adherence. METHODS: Post hoc analysis of a quality improvement initiative in which English- and Spanish-speaking patients from a county-based public health system were randomly assigned to receive health coaching or usual care. An unlicensed, trained health coach called patients three times to resolve barriers to adherence. A per-protocol analysis was conducted for adherence measures collected by device modem at baseline and 30 days. RESULTS: Of 131 people for whom device data were available, 56 were randomized to health coaching and 75 to usual care. At baseline, 47.3% of patients had used their device at any time in the past 30 days, with a mean of 2 hours of use per night. At 30 days, adjusting for baseline, patients in the coaching arm were more likely than usual care patients to use their device (55.4% vs. 41.3%, p = 0.03), and they increased their use for 0.4 hours over usual care (p = 0.04). CONCLUSION: This pilot study suggests that a low-cost intervention could be effective at improving PAP adherence, even in a population known to have poor adherence and among long-term PAP users with poor adherence. Future research may examine whether a higher-touch intervention or one using videoconferencing yields greater improvements. This promising intervention warrants further study.

The impact of increasing general hospital admissions on Consultation-Liaison Psychiatry.

OBJECTIVE: The objective of this study was to identify changes in patients referred to CLP at a typical inner urban teaching hospital over two decades in the context of increased hospital admissions. METHOD: Multivariate analyses were conducted on data collected for all referrals to CLP at Royal Melbourne Hospital between 1998 and 2017. Analyses were conducted with reason for referral, current psychiatric contact, psychiatric diagnosis, discharge destination and follow up as dependent variables, and the year and annual hospital admissions as independent variables. RESULTS: Annual hospital admissions grew at a rate (4.6%), greater than the annual increase in beds (2.0%). Psychosis, suicide attempt, past psychiatric history and behaviour became more common reasons for referral, whilst depression and somatisation became less common. Transfers to and from mental health inpatient units increased. CONCLUSIONS: An increasing proportion of patients seen by CLP have 'acute' problems. Patients with somatisation and depression are seen less frequently. These findings indicate that CLP services need to provide timely assessment and work closely with other elements of the local mental health service in order to optimise patient flow and ensure continuity of care. Local strategies may be required to ensure an adequate breadth of experience for trainees.

Lay Health Coaching to Increase Appropriate Inhaler Use in COPD: A Randomized Controlled Trial.

PURPOSE: Poor adherence to medications is more prevalent for chronic obstructive pulmonary disease (COPD) than for other chronic conditions and is associated with unfavorable health outcomes. Few interventions have successfully improved adherence for COPD medications; none of these use unlicensed health care personnel. We explored the efficacy of lay health coaches to improve inhaler adherence and technique. METHODS: Within a randomized controlled trial, we recruited English- and Spanish-speaking patients with moderate to severe COPD from urban, public primary care clinics serving a low-income, predominantly African American population. Participants were randomized to receive 9 months of health coaching or usual care. Outcome measures included self-reported adherence to inhaled controller medications in the past 7 days and observed technique for all inhalers. We used generalized linear models, controlling for baseline values and clustering by site. RESULTS: Baseline adherence and inhaler technique were uniformly poor and did not differ by study arm. At 9 months, health-coached patients reported a greater number of days of adherence compared with usual care patients (6.4 vs 5.5 days; adjusted P = .02) and were more likely to have used their controller inhalers as prescribed for 5 of the last 7 days (90% vs 69%; adjusted P = .008). They were more than 3 times as likely to demonstrate perfect technique for all inhaler devices (24% vs 7%; adjusted P = .01) and mastery of essential steps (40% vs 11%; adjusted P <.001). CONCLUSIONS: Health coaching may provide a scalable model that can improve care for people living with COPD.