Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia.

BACKGROUND: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk evaluation. METHODS: A multidisciplinary committee created an infectious diseases DOOR endpoint customized for HABP/VABP, incorporating infectious complications, serious adverse events, and mortality. We applied this to 2 previously completed, large randomized controlled trials for HABP/VABP. ZEPHyR compared vancomycin to linezolid and VITAL compared linezolid to tedizolid. For each trial, we evaluated the DOOR distribution and probability, including DOOR component and partial credit analyses. We also applied DOOR in subgroup analyses. RESULTS: In both trials, the HABP/VABP DOOR demonstrated similar overall clinical outcomes between treatment groups. In ZEPHyR, the probability that a participant treated with linezolid would have a more desirable outcome than a participant treated with vancomycin was 50.2% (95% confidence interval [CI], 45.1%--55.3%). In VITAL, the probability that a participant treated with tedizolid would have a more desirable outcome than a participant treated with linezolid was 48.7% (95% CI, 44.8%-52.6%). The DOOR component analysis revealed that participants treated with tedizolid had a less desirable outcome than those treated with linezolid when considering clinical response alone. However, participants with decreased renal function had improved overall outcomes with tedizolid. CONCLUSIONS: The HABP/VABP DOOR provided more granular information about clinical outcomes than is typically presented in clinical trials. HABP/VABP trials would benefit from prospectively using DOOR.

Exploration of a Potential DOOR Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Using Six Registrational Trials for Antibacterial Drugs.

BACKGROUND: Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here, we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP). METHODS: Through comprehensive examination of data from nearly 4,000 participants enrolled in six registrational trials for HABP/VABP submitted to the FDA between 2005-2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that a participant assigned to the study treatment arm would have a more favorable overall DOOR or component outcome than a participant assigned to comparator. RESULTS: DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 48.3% to 52.9% and were not statistically different. There were no significant differences between treatment arms in the component analyses. Though infectious complications and serious adverse events occurred more frequently in ventilated participants compared to non-ventilated participants, the types of events were similar. CONCLUSIONS: Through a data-driven approach, we constructed and applied a potential DOOR endpoint for HABP/VABP trials. The inclusion of syndrome-specific events may help to better delineate and evaluate participant experiences and outcomes in future HABP/VABP trials and could help inform data collection and trial design.

Optimal hepatitis C treatment adherence patterns and sustained virologic response among people who inject drugs: The HERO study.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are highly effective for treating HCV infection even among people who inject drugs (PWID). Yet, little is known about patients' adherence patterns and their association with sustained virologic response (SVR) rates. We aimed to summarize various adherence patterns and determine their associations with SVR. METHODS: Electronic blister packs were used to measure daily adherence to once-a-day sofosbuvir/velpatasvir during the 12-week treatment period among active PWIDs. Blister pack data were available for 496 participants who initiated DAAs for whom SVR status was known. Adherence was summarized in multiple patterns, such as total adherent days, consecutive missed days, and early discontinuations. Thresholds for adherence patterns associated with >90% SVR rates were also determined. RESULTS: The overall SVR rate was 92.7%, with a median adherence rate of 75%. All adherence patterns indicating greater adherence were significantly associated with achieving SVR. Participant groups with ≥50% (>42/84) adherent days or <26 consecutive missed days achieved an SVR rate of >90%. Greater total adherent days during 9-12 weeks and no early discontinuation were significantly associated with higher SVR rates only in those with <50% adherence. Participants with first month discontinuation and ≥2 weeks of treatment interruption had low SVR rates, 25% and 85%, respectively. However, greater adherent days were significantly associated with SVR (adjusted odds ratio 1.10; 95% CI 1.04-1.16; p <0.001) even among participants with ≥14 consecutive missed days. CONCLUSIONS: High SVR rates can be achieved in the PWID population despite suboptimal adherence. Encouraging patients to take as much medication as possible, with <2 weeks consecutive missed days and without early discontinuation, was found to be important for achieving SVR. IMPACT AND IMPLICATIONS: People who inject drugs can be cured of HCV in >90% of cases, even with relatively low adherence to direct-acting antivirals, but early discontinuations and long treatment interruptions can significantly reduce the likelihood of achieving cure. Clinicians should encourage people who inject drugs who are living with HCV to adhere daily to direct-acting antivirals as consistently as possible, but if any days are interrupted, to continue and complete treatment. These results from the HERO study are important for patients living with HCV, clinicians, experts writing clinical guidelines, and payers. CLINICAL TRIAL NUMBER: NCT02824640.

Overreporting of adherence to hepatitis C direct-acting antiviral therapy and sustained virologic response among people who inject drugs in the HERO study.

BACKGROUND: Self-reported adherence to direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) among persons who inject drugs (PWID) is often an overreport of objectively measured adherence. The association of such overreporting with sustained virologic response (SVR) is understudied. This study among PWID aimed to determine a threshold of overreporting adherence that optimally predicts lower SVR rates, and to explore correlates of the optimal overreporting threshold. METHODS: This study analyzed per-protocol data of participants with adherence data (N = 493) from the HERO (Hepatitis C Real Options) study. Self-reported and objective adherence to a 12-week DAA regimen were measured using visual analogue scales and electronic blister packs, respectively. The difference (Δ) between self-reported and objectively measured adherence was calculated. We used the Youden index based on receiver operating characteristic (ROC) curve analysis to identify an optimal threshold of overreporting for predicting lower SVR rates. Factors associated with the optimal threshold of overreporting were identified by comparing baseline characteristics between participants at/above versus those below the threshold. RESULTS: The self-reported, objective, and Δ adherence averages were 95.1% (SD = 8.9), 75.9% (SD = 16.3), and 19.2% (SD = 15.2), respectively. The ≥ 25% overreporting threshold was determined to be optimal. The SVR rate was lower for ≥ 25% vs. < 25% overreporting (86.7% vs. 95.8%, p <.001). The factors associated with ≥ 25% Δ adherence were unemployment; higher number of days and times/day of injecting drugs; higher proportion of positive urine drug screening for amphetamine, methamphetamine, and oxycodone, and negative urine screening for THC (tetrahydrocannabinol)/cannabis. CONCLUSIONS: Self-reported DAA adherence was significantly greater than objectively measured adherence among PWID by 19.2%. Having ≥ 25% overreported adherence was associated with optimal prediction of lower SVR rates. PWID with risk factors for high overreporting may need to be more intensively managed to promote actual adherence.

Cerebral folate deficiency: a treatable cause of late deterioration in epilepsy with developmental delay.

A 25-year-old woman with childhood-onset refractory epilepsy and developmental delay experienced a gradually progressive marked deterioration in mobility and seizure control, with language regression. Investigation identified a homozygous deletion within the contactin-associated protein-like 2 gene (CNTNAP2), underlying her early presentation, but also cerebral folate deficiency that most likely contributed to her later deterioration. Following antiseizure medication adjustment and treatment with folinic acid, she stabilised with improved seizure control and limited improvement in language and motor function; she has remained neurologically stable for more than a decade. That the previously observed neurological decline was halted by folinic acid replacement supports this being due to cerebral folate deficiency. Metabolic conditions are less well recognised in adults and can be under-diagnosed. They are potentially treatable and should be considered even in the presence of another cause, particularly when the presentation is not fully compatible.

The Future Ain't What It Used to Be Out With the Old In With the Better: Antibacterial Resistance Leadership Group Innovations.

Clinical research networks conduct important studies that would not otherwise be performed by other entities. In the case of the Antibacterial Resistance Leadership Group (ARLG), such studies include diagnostic studies using master protocols, controlled phage intervention trials, and studies that evaluate treatment strategies or dynamic interventions, such as sequences of empiric and definitive therapies. However, the value of a clinical research network lies not only in the results from these important studies but in the creation of new approaches derived from collaborative thinking, carefully examining and defining the most important research questions for clinical practice, recognizing and addressing common but suboptimal approaches, and anticipating that the standard approaches of today may be insufficient for tomorrow. This results in the development and implementation of new methodologies and tools for the design, conduct, analyses, and reporting of research studies. These new methodologies directly impact the studies conducted within the network and have a broad and long-lasting impact on the field, enhancing the scientific value and efficiency of generations of research studies. This article describes innovations from the ARLG in diagnostic studies, observational studies, and clinical trials evaluating interventions for the prevention and treatment of antibiotic-resistant bacterial infections.

Improving Traditional Registrational Trial End Points: Development and Application of a Desirability of Outcome Ranking End Point for Complicated Urinary Tract Infection Clinical Trials.

BACKGROUND: Traditional end points used in registrational randomized, controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials that incorporates benefits and risks of novel treatment strategies and provides a global assessment of patient experience. METHODS: Through a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience, we developed a DOOR end point for infectious disease syndromes and demonstrated how this could be applied to 3 registrational drug trials (ZEUS, APEKS-cUTI, and DORI-05) for complicated urinary tract infections (cUTIs). ZEUS compared fosfomycin to piperacillin/tazobactam, APEKS-cUTI compared cefiderocol to imipenem, and DORI-05 compared doripenem to levofloxacin. Using DOOR, we estimated the probability of a more desirable outcome with each investigational antibacterial drug. RESULTS: In each RCT, the DOOR distribution was similar and the probability that a patient in the investigational arm would have a more desirable outcome than a patient in the control arm had a 95% confidence interval containing 50%, indicating no significant difference between treatment arms. DOOR facilitated improved understanding of potential trade-offs between clinical efficacy and safety. Partial credit and subgroup analyses also highlight unique attributes of DOOR. CONCLUSIONS: DOOR can effectively be used in registrational cUTI trials. The DOOR end point presented here can be adapted for other infectious disease syndromes and prospectively incorporated into future clinical trials.

Exploration of a Potential Desirability of Outcome Ranking Endpoint for Complicated Intra-Abdominal Infections Using 9 Registrational Trials for Antibacterial Drugs.

BACKGROUND: Desirability of outcome ranking (DOOR) is a novel approach to clinical trial design that incorporates safety and efficacy assessments into an ordinal ranking system to evaluate overall outcomes of clinical trial participants. Here, we derived and applied a disease-specific DOOR endpoint to registrational trials for complicated intra-abdominal infection (cIAI). METHODS: Initially, we applied an a priori DOOR prototype to electronic patient-level data from 9 phase 3 noninferiority trials for cIAI submitted to the US Food and Drug Administration between 2005 and 2019. We derived a cIAI-specific DOOR endpoint based on clinically meaningful events that trial participants experienced. Next, we applied the cIAI-specific DOOR endpoint to the same datasets and, for each trial, estimated the probability that a participant assigned to the study treatment would have a more desirable DOOR or component outcome than if assigned to the comparator. RESULTS: Three key findings informed the cIAI-specific DOOR endpoint: (1) a significant proportion of participants underwent additional surgical procedures related to their baseline infection; (2) infectious complications of cIAI were diverse; and (3) participants with worse outcomes experienced more infectious complications, more serious adverse events, and underwent more procedures. DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 47.4% to 50.3% and were not significantly different. Component analyses depicted risk-benefit assessments of study treatment versus comparator. CONCLUSIONS: We designed and evaluated a potential DOOR endpoint for cIAI trials to further characterize overall clinical experiences of participants. Similar data-driven approaches can be utilized to create other infectious disease-specific DOOR endpoints.

Acute Effects of Ketamine on Intracranial Pressure in Children With Severe Traumatic Brain Injury.

OBJECTIVES: The acute cerebral physiologic effects of ketamine in children have been incompletely described. We assessed the acute effects of ketamine on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in children with severe traumatic brain injury (TBI). DESIGN: In this retrospective observational study, patients received bolus doses of ketamine for sedation or as a treatment for ICP crisis (ICP > 20 mm Hg for > 5 min). Administration times were synchronized with ICP and CPP recordings at 1-minute intervals logged in an automated database within the electronic health record. ICP and CPP were each averaged in epochs following drug administration and compared with baseline values. Age-based CPP thresholds were subtracted from CPP recordings and compared with baseline values. Trends in ICP and CPP over time were assessed using generalized least squares regression. SETTING: A 30-bed tertiary care children's hospital PICU. PATIENTS: Children with severe TBI who underwent ICP monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data from 33 patients, ages 1 month to 16 years, 22 of whom received bolus doses of ketamine, with 127 doses analyzed. Demographics, patient, and injury characteristics were similar between patients who did versus did not receive ketamine boluses. In analysis of the subset of ketamine doses used only for sedation, there was no significant difference in ICP or CPP from baseline. Eighteen ketamine doses were given during ICP crises in 11 patients. ICP decreased following these doses and threshold-subtracted CPP rose. CONCLUSIONS: In this retrospective, exploratory study, ICP did not increase following ketamine administration. In the setting of a guidelines-based protocol, ketamine was associated with a reduction in ICP during ICP crises. If these findings are reproduced in a larger study, ketamine may warrant consideration as a treatment for intracranial hypertension in children with severe TBI.

Margarita glasses and high heels: How attention to shape, age, and vocabulary impacts children's recognition of typical and atypical exemplars.

Children's ability to recognize object shape is foundational for successful early word learning. However, the prototypical shape of objects may not be easily accessible-take margarita glasses, for instance. The current study examined 304 U.S. children 17- to 42-month-old (152 females) from 2017 to 2020, asking how shape, age, and vocabulary abilities predict recognition of everyday objects. Children's ability to recognize objects increases with age and vocabulary, replicating prior work. Moreover, performance was partially moderated by object's typicality and shape features, and children's own attention to shape (shape bias) may mediate the effect, especially with prototypically shaped objects. The current study highlights how both child-specific variables and context features interact to shape language abilities, underscoring the emergent and multi-causal nature of word learning.

Podocytopathies related to either COVID-19 infection or its vaccination, our experience and literature review.

Coronavirus disease 2019 (COVID-19) affects several organs including the kidney resulting in acute kidney injury (AKI) and variants of podocytopathies. From the beginning to the middle period of the COVID-19 pandemic, we have collected eight renal biopsies with various renal diseases including 4 podocytopathies. In addition, from the middle period to the near end of the COVID-19 pandemic, we have seen two of the patients who developed nephrotic syndrome following COVID-19 vaccination. Three of 4 podocytopathies were collapsing glomerulopathy (also called collapsing focal segmental glomerulosclerosis) and the fourth was a minimal change disease (MCD). Two of three collapsing glomerulopathy were found in African American patients, one of who was tested positive for having the high-risk allele APOL-1 G1. In addition, the two renal biopsies showed either MCD or replaced MCD following COVID-19 vaccination. MCD can be a rare complication following COVID-19 infection and COVID-19 vaccination, raising the question if there are similar antigens induced by the infection or by the vaccination that trigger the MCD. This article reports our experience of diagnosing podocytopathies related to either COVID-19 infection or its vaccination and provides a literature review regarding the incidence and potential pathophysiology in the field.

Medical management of secondary postpartum haemorrhage: A prospective cohort study.

BACKGROUND: Secondary postpartum haemorrhage (PPH) complicates ~1% of pregnancies and can cause serious maternal morbidity. However, evidence guiding optimal management is scarce and often based on case series and expert opinion. AIMS: To measure the success of primary medical therapy in managing secondary PPH and to identify factors associated with need for surgical management. MATERIALS AND METHODS: Postpartum patients presenting to a tertiary women's hospital emergency department between July 2020 and October 2021 with secondary PPH were recruited. Data from the acute presentation were prospectively collected. Antenatal and intrapartum data were collected from medical record review. The primary outcome was the success of medical management for secondary PPH, defined by the implementation of medical or expectant measures without subsequent need for surgical intervention. RESULTS: One-hundred and twenty patients underwent primary medical management for secondary PPH. Ninety-eight (82%) were managed successfully with medical management and 22 (18%) required surgery. Medical management involved misoprostol (n = 33; 27.5%), antibiotics (n = 108; 90%), and less commonly other uterotonics (n = 6; 5%). Factors associated with lower rates of successful medical management included: antecedent manual removal of placenta (MROP) (odds ratio (OR) 0.2, P = 0.047), primary PPH ≥500 mL (OR 0.39, P = 0.048) or ≥1 L (OR 0.24, P = 0.009), >200 mL blood loss at presentation (OR 0.17, P = 0.015), increasing time post-delivery (OR 0.84, P = 0.044), retained products of conception (RPOC) on ultrasound (OR 0.024, P = 0.001) and vaginal birth (OR 0.27, P = 0.027). CONCLUSION: Medical management was highly successful. Vaginal birth, MROP, primary PPH, RPOC on ultrasound and increasing time post-delivery were associated with increased need for surgical management.

Contemporary Nurse-Midwifery Care in Colorado: A Survey of Certified Nurse-Midwife Practices in Hospital and Community Settings.

Lack of access to birth facilities and maternity care providers has contributed to rising US maternal mortality and morbidity rates, especially among women in rural areas. Evidence supports the increased use of midwives as a potential solution for access-to-care issues. This observational survey was conducted to identify the practice environment for Certified Nurse-Midwives® in Colorado for the purpose of informing future workforce expansion. Study results indicate that midwives provide services aligned with the midwifery model of care and have mostly autonomous practice in hospitals where midwifery practices are already established. However, there is limited use of midwives, as fewer than half of Colorado's 69 birthing hospitals have midwifery practices, and financial constraint created by low Medicaid reimbursement could be a limiting factor in establishing new midwifery practices. Policy recommendations based on survey results include (a) support for midwifery education and workforce development, (b) removal of hospital-level restrictions for privileges of midwives, and (c) consideration for public payment models that promote expansion of midwifery practices.

Prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa and association with clinical outcomes in patients: an observational study.

OBJECTIVES: To describe the prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa (CRPA) and evaluate the association with clinical outcomes. METHODS: Colistin heteroresistance was evaluated in CRPA isolates collected from patients without cystic fibrosis in Atlanta, Georgia, USA using two definitions: HR1, growth at 4 and 8 mg/L of colistin at a frequency ≥1 × 10-6 the main population; and HR2, growth at a colistin concentration ≥8× the MIC of the main population at a frequency ≥1 × 10-7. A modified population analysis profile (mPAP) technique was compared with reference PAP for detecting heteroresistance. For adults hospitalized at the time of or within 1 week of CRPA culture, multivariable logistic regression estimated the association between heteroresistance and 90 day mortality. RESULTS: Of 143 colistin-susceptible CRPA isolates, 8 (6%) met the HR1 definition and 37 (26%) met the HR2 definition. Compared with the reference PAP, mPAP had a sensitivity and specificity of 50% and 100% for HR1 and 32% and 99% for HR2. Of 82 hospitalized patients, 45 (56%) were male and the median age was 63 years (IQR 49-73). Heteroresistance was not associated with 90 day mortality using HR1 (0% in heteroresistant versus 22% in non-heteroresistant group; P = 0.6) or HR2 (12% in heteroresistant versus 24% in non-heteroresistant group; P = 0.4; adjusted OR 0.8; 95% CI 0.2-3.4). CONCLUSIONS: Colistin heteroresistance was identified in up to 26% of patients with CRPA in our sample, although the prevalence varied depending on the definition. We did not observe an apparent association between colistin heteroresistance and 90 day mortality.

Multicenter Study Evaluating Nitrous Oxide Use for Labor Analgesia at High- and Low-Altitude Institutions.

BACKGROUND: Nitrous oxide (N2O) has been used nationally as an analgesic in many clinical settings. While neuraxial analgesia is still the most commonly used labor analgesic in the United States, there is increasing use of N2O in labor. Given the reduction in the partial pressure of gases at a higher altitude, N2O has been reported to have reduced analgesic properties. However, there is no study to date evaluating the impact of altitude on labor analgesia and N2O. METHODS: We conducted a multicenter retrospective data analysis of a N2O registry collected from 4 institutions over a 3-year period. We compared the impact of altitude on 50% N2O administration for labor analgesia, conversion rates to another analgesic modality, as well as collected side effect frequencies and conversion predictors. Multivariable regression models were used to compare clinical characteristics and outcomes between parturients at high and low altitudes, while adjusting for race, ethnicity, education, and age (logistic and linear regressions for categorical and quantitative outcomes, respectively). RESULTS: A total of 1856 laboring parturients (age 18-50) were included in the analysis. The odds of converting from 50% N2O to another analgesic modality had no statistically significant difference between high- versus low-altitude institutions (adjusted odds ratio [aOR], 1.13; 95% confidence interval [CI], 0.90-1.42; P = .3). Yet, when parturients at low altitude converted from N2O, they were more likely (aOR, 3.03; 95% CI, 1.59-5.88) to choose neuraxial analgesia instead of another analgesic modality when compared to high-altitude parturients. This is possibly due to higher epidural rates at the low-altitude institutions. When parturients at high altitude did convert into another modality, they were more likely (aOR, 2.19; 95% CI, 1.14-4.21) to convert due to inadequate pain relief compared to low-altitude parturients; however, missing data may have affected this finding. Laboring individuals at low altitude were significantly more likely to experience side effects (aOR, 2.13; 95% CI, 1.45-3.12). Those requiring labor augmentation, assisted vaginal, or cesarean delivery converted to neuraxial analgesia significantly more often than those that delivered via spontaneous vaginal delivery (P < .05) in both high- and low-altitude groups. CONCLUSIONS: This is the first study evaluating 50% N2O as a labor analgesic at high altitude. As expected, we found lower side effects at high altitude, likely due to the lower partial pressure of N2O. However, there was not a statistically significant increase in conversion from N2O to another analgesic modality at high altitude and no clinically significant differences in neonatal outcomes.

Case Commentary: Uncertainty in Evaluating Treatment Outcomes in Carbapenem-Resistant Acinetobacter baumannii Infections.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are challenging to treat and associated with poor clinical outcomes. In this issue, sulbactam-durlobactam, a novel ß-lactam-ß-lactamase inhibitor, was used with cefiderocol to successfully treat CRAB pneumonia. While this report and in vitro data are encouraging, determining the impact of treatment regimens on clinical outcomes after CRAB infections is not straightforward. Therefore, careful evaluation in pathogen-directed randomized controlled trials is needed to determine the optimal treatment of CRAB infections.

A sequential explanatory study of the employment experiences of population-based breast, colorectal, and prostate cancer survivors.

PURPOSE: Cancer treatment often leads to work disruptions including loss of income, resulting in long-term financial instability for cancer survivors and their informal caregivers. METHODS: In this sequential explanatory study, we conducted a cross-sectional survey of employment experiences among ethnically diverse, working-age individuals diagnosed with breast, colorectal, or prostate cancer. Following the survey, we conducted semi-structured interviews with cancer survivors and informal caregivers to explore changes in employment status and coping techniques to manage these changes. RESULTS: Among employed survivors (n = 333), cancer caused numerous work disruptions including issues with physical tasks (53.8%), mental tasks (46.5%) and productivity (76.0%) in the workplace. Prostate cancer survivors reported fewer work disruptions than female breast and male and female colorectal cancer survivors. Paid time off and flexible work schedules were work accommodations reported by 52.6% and 36.3% of survivors, respectively. In an adjusted regression analysis, household income was positively associated with having received a work accommodation. From the qualitative component of the study (survivors n = 17; caregivers n = 11), three key themes emerged: work disruptions, work accommodations, and coping mechanisms to address the disruptions. Survivors and caregivers shared concerns about lack of support at work and resources to navigate issues caused by changes in employment. CONCLUSIONS: This study characterized employment changes among a diverse group of cancer survivors. Work accommodations were identified as a specific unmet need, particularly among low-income cancer survivors. Addressing changes in employment among specific groups of cancer survivors and caregivers is critical to mitigate potential long-term consequences of cancer.

Analytical validation of the Percepta genomic sequencing classifier; an RNA next generation sequencing assay for the assessment of Lung Cancer risk of suspicious pulmonary nodules.

BACKGROUND: Bronchoscopy is a common procedure used for evaluation of suspicious lung nodules, but the low diagnostic sensitivity of bronchoscopy often results in inconclusive results and delays in treatment. Percepta Genomic Sequencing Classifier (GSC) was developed to assist with patient management in cases where bronchoscopy is inconclusive. Studies have shown that exposure to tobacco smoke alters gene expression in airway epithelial cells in a way that indicates an increased risk of developing lung cancer. Percepta GSC leverages this idea of a molecular "field of injury" from smoking and was developed using RNA sequencing data generated from lung bronchial brushings of the upper airway. A Percepta GSC score is calculated from an ensemble of machine learning algorithms utilizing clinical and genomic features and is used to refine a patient's risk stratification. METHODS: The objective of the analysis described and reported here is to validate the analytical performance of Percepta GSC. Analytical performance studies characterized the sensitivity of Percepta GSC test results to input RNA quantity, the potentially interfering agents of blood and genomic DNA, and the reproducibility of test results within and between processing runs and between laboratories. RESULTS: Varying the amount of input RNA into the assay across a nominal range had no significant impact on Percepta GSC classifier results. Bronchial brushing RNA contaminated with up to 10% genomic DNA by nucleic acid mass also showed no significant difference on classifier results. The addition of blood RNA, a potential contaminant in the bronchial brushing sample, caused no change to classifier results at up to 11% contamination by RNA proportion. Percepta GSC scores were reproducible between runs, within runs, and between laboratories, varying within less than 4% of the total score range (standard deviation of 0.169 for scores on 4.57 scale). CONCLUSIONS: The analytical sensitivity, analytical specificity, and reproducibility of Percepta GSC laboratory results were successfully demonstrated under conditions of expected day to day variation in testing. Percepta GSC test results are analytically robust and suitable for routine clinical use.

Screening, brief intervention, and referral to treatment (SBIRT) expansion of training to non-physician healthcare graduate students: Counseling psychology, nursing, occupational therapy, physical therapy, and physician assistant studies.

BACKGROUND: Although Screening, Brief Intervention and Referral to Treatment (SBIRT) has now been disseminated in many areas of the United States (US), much remains to be discovered about the training outcomes of non-physician professional trainees such as nurses, physician assistants, physical therapists, occupational therapists, and psychologists following SBIRT training. Methods: Training in SBIRT, an evidence-based approach to screening substance use, was embedded into five health science graduate curricula: Physician Assistant Studies, Nursing, Occupational Therapy, Physical Therapy, and Psychology. The SBIRT curriculum was adapted for each profession to include a brief introductory module addressing SBIRT's relevance for each profession, as well as profession-specific case examples and terminology. Using a nonequivalent group design, participants completed pre-and post-training assessments of substance use related attitudes, perceived competency and knowledge. Data were analyzed using a parametric test to compare pre- and post-differences. Results: Findings suggest improved attitudes as well as increased perceived competencies and core knowledge following the graduate-curriculum embedded SBIRT training, as well as between group differences on the same variables. Conclusions: SBIRT training of non-physician healthcare graduate student-trainees is a feasible training activity and results in improved trainee attitudes, perceived competency, and knowledge. SBIRT training embedded into graduate health science curricula offers an early foundation to this well-established, universal screening approach.

Meeting the Challenge of Perinatal Care in Rural Communities.

The complexities of providing quality perinatal care within rural communities provide significant challenges to providers and policy makers. Provision of healthcare in rural communities is challenging on individual as well as community-based levels. A quality improvement lens is applied to consider key challenges that pertain to patients, providers, place, and policy. Potential solutions from a provider perspective include nurse-midwifery care and inclusion of advanced practice providers in a variety of specialties in addition to creating care models for registered nurses to practice at the top of their scope. To enhance access in the rural place, telehealth and coordination activities are recommended. Finally, policy approaches such as Perinatal Care Collaboratives, Area Health Education Centers, and enhanced financial resources to eliminate socioeconomic disparities will enhance perinatal care in rural communities.