Identification and interest of molecular markers to monitor plant Pi status.

BACKGROUND: Inorganic phosphate (Pi) is the sole source of phosphorus for plants. It is a limiting factor for plant yield in most soils worldwide. Due to economic and environmental constraints, the use of Pi fertilizer is and will be more and more limited. Unfortunately, evaluation of Pi bioavailability or Pi starvation traits remains a tedious task, which often does not inform us about the real Pi plant status. RESULTS: Here, we identified by transcriptomic studies carried out in the plant model Arabidopsis thaliana, early roots- or leaves-conserved molecular markers for Pi starvation, exhibiting fast response to modifications of phosphate nutritional status. We identified their homologues in three crops (wheat, rapeseed, and maize) and demonstrated that they offer a reliable opportunity to monitor the actual plant internal Pi status. They turn out to be very sensitive in the concentration range of 0-50 µM which is the most common case in the vast majority of soils and situations where Pi hardly accumulates in plants. Besides in vitro conditions, they could also be validated for plants growing in the greenhouse or in open field conditions. CONCLUSION: These markers provide valuable physiological tools for plant physiologists and breeders to assess phosphate bio-availability impact on plant growth in their studies. This also offers the opportunity to cope with the rising economical (shortage) and societal problems (pollution) resulting from the management of this critical natural resource.

TCD screening and spending among children with sickle cell anemia.

OBJECTIVES: National guidelines recommend that children with sickle cell anemia receive annual transcranial Doppler (TCD) screening to assess stroke risk. Our objectives were to estimate the rate of TCD screening among privately insured children with sickle cell anemia, estimate out-of-pocket spending for TCD screening, and evaluate the association between TCD screening and enrollment in high-deductible health plans (HDHPs). STUDY DESIGN: Cross-sectional. METHODS: Using the 2009-2017 IBM MarketScan Commercial Database, we identified children aged 2 to 15 years who met a validated claims-based definition of sickle cell anemia. We calculated the proportion of children receiving annual TCD screening and out-of-pocket spending per TCD screen. Using logistic regression with generalized estimating equations, we modeled the receipt of annual TCD screening as a function of HDHP enrollment, controlling for demographics and year. RESULTS: The 2519 children in the analysis accounted for 7197 person-years of enrollment; 14% of person-years were from HDHP enrollees. During 2009-2017, the proportion of children receiving TCD screening ranged from 40% to 44%. Median out-of-pocket spending for TCD screening was $20 overall and $65 among HDHP enrollees. Out-of-pocket spending exceeded $100 for 27% of all screens and 42% of screens among HDHP enrollees. HDHP enrollment was not associated with TCD screening (adjusted odds ratio, 0.99; 95% CI, 0.85-1.15). CONCLUSIONS: Among privately insured children with sickle cell anemia, fewer than half received annual TCD screening. Out-of-pocket spending exceeded $100 for 27% of TCD screens. Although HDHP enrollment was not associated with TCD screening, additional studies are needed to assess whether cost sharing might deter this screening.

Transcription Factor Dynamics in Cross-Regulation of Plant Hormone Signaling Pathways.

Cross-regulation between hormone signaling pathways is indispensable for plant growth and development. However, the molecular mechanisms by which multiple hormones interact and co-ordinate activity need to be understood. Here, we generated a cross-regulation network explaining how hormone signals are integrated from multiple pathways in etiolated Arabidopsis (Arabidopsis thaliana) seedlings. To do so we comprehensively characterized transcription factor activity during plant hormone responses and reconstructed dynamic transcriptional regulatory models for six hormones; abscisic acid, brassinosteroid, ethylene, jasmonic acid, salicylic acid and strigolactone/karrikin. These models incorporated target data for hundreds of transcription factors and thousands of protein-protein interactions. Each hormone recruited different combinations of transcription factors, a subset of which were shared between hormones. Hub target genes existed within hormone transcriptional networks, exhibiting transcription factor activity themselves. In addition, a group of MITOGEN-ACTIVATED PROTEIN KINASES (MPKs) were identified as potential key points of cross-regulation between multiple hormones. Accordingly, the loss of function of one of these (MPK6) disrupted the global proteome, phosphoproteome and transcriptome during hormone responses. Lastly, we determined that all hormones drive substantial alternative splicing that has distinct effects on the transcriptome compared with differential gene expression, acting in early hormone responses. These results provide a comprehensive understanding of the common features of plant transcriptional regulatory pathways and how cross-regulation between hormones acts upon gene expression.

Age, race, insurance type, and digital divide index are associated with video visit completion for patients seen for oncologic care in a large hospital system during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic drove rapid adoption of telehealth across oncologic specialties. This revealed barriers to telehealth access and telehealth-related disparities. We explored disparities in telehealth access in patients with cancer accessing oncologic care. MATERIALS/METHODS: Data for all unique patient visits at a large academic medical center were acquired pre- and intra-pandemic (7/1/2019-12/31/2020), including visit type (in-person, video, audio only), age, race, ethnicity, rural/urban (per zip code by Federal Office of Rural Health Policy), distance from medical facility, insurance, and Digital Divide Index (DDI; incorporates technology/internet access, age, disability, and educational attainment metrics by geographic area). Pandemic phases were identified based on visit dynamics. Multivariable logistic regression models were used to examine associations of these variables with successful video visit completion. RESULTS: Data were available for 2,398,633 visits for 516,428 patients across all specialties. Among these, there were 253,880 visits from 62,172 patients seen in any oncology clinic. Dramatic increases in telehealth usage were seen during the pandemic (after 3/16/2020). In multivariable analyses, patient age [OR: 0.964, (95% CI 0.961, 0.966) P<0.0001], rural zip code [OR: 0.814 (95% CI 0.733, 0.904) P = 0.0001], Medicaid enrollment [OR: 0.464 (95% CI 0.410, 0.525) P<0.0001], Medicare enrollment [OR: 0.822 (95% CI 0.761, 0.888) P = 0.0053], higher DDI [OR: 0.903 (95% CI 0.877, 0.930) P<0.0001], distance from the facility [OR: 1.028 (95% CI 1.021, 1.035) P<0.0001], black race [OR: 0.663 (95% CI 0.584, 0.753) P<0.0001], and Asian race [OR: 1.229 (95% CI 1.022, 1.479) P<0.0001] were associated with video visit completion early in the pandemic. Factors related to video visit completion later in the pandemic and within sub-specialties of oncology were also explored. CONCLUSIONS: Patients from older age groups, those with minority backgrounds, and individuals from areas with less access to technology (high DDI) as well as those with Medicare or Medicaid insurance were less likely to use video visits. With greater experience through the pandemic, disparities were not mitigated. Further efforts are required to optimize telehealth to benefit all patients and avoid increasing disparities in care delivery.

Predictors of Video versus Audio-Only Telehealth Use among Urological Patients.

Introduction: During the COVID-19 public health emergency, telehealth use grew due to regulatory and reimbursement surrounding the use of video and audio-only visits for the evaluation and management of patients. Methods: We retrospectively reviewed patients seeking outpatient urological care from April 1, 2020 to June 30, 2020 at a urological tertiary care center. Our study was designed to determine the relative effect of demographic, socioeconomic and geographic variables on the likelihood of using video compared to an audio-only telehealth. Results: We identified 4,744 unique patients who had a urological telehealth visit. Demographic factors associated with lower probability of utilizing video telehealth were older age (ages >65 years, average marginal effect [AME] -38.3, 95% CI -40.8, -34.7), Black/African American race and American Indian and Alaska Native race (AME -9.7, 95% CI -10.7, -7.1; AME -17.1, 95% CI -18.8, -13.7, respectively), interpreter use (AME -4.5, 95% CI -5, -3.1), Medicaid insurance (AME -13.3, 95% CI -14.8, -9.8), rural residence and living in area with low broadband Internet access (AME -12.8, 95% CI -14.1, -9.1). Conclusions: Forty-four percent of patients used audio-only visits to connect with their urologists. Age, ethnicity, rurality, type of insurance and broadband access all impacted the type of telehealth used to receive urological care. Without coverage and reimbursement of audio-only visits, video telehealth could exacerbate health disparities in access to urological care.

Association Between Default Number of Opioid Doses in Electronic Health Record Systems and Opioid Prescribing to Adolescents and Young Adults Undergoing Tonsillectomy.

Importance: In prior studies, decreasing the default number of doses in opioid prescriptions written in electronic health record systems reduced opioid prescribing. However, these studies did not rigorously assess patient-reported outcomes, and few included pediatric patients. Objective: To evaluate the association between decreasing the default number of doses in opioid prescriptions written in electronic health record systems and opioid prescribing and patient-reported outcomes among adolescents and young adults undergoing tonsillectomy. Design, Setting, and Participants: This nonrandomized clinical trial included adolescents and young adults aged 12 to 50 years undergoing tonsillectomy from October 1, 2019, through July 31, 2021, at a tertiary medical center. The treatment group comprised patients from a pediatric otolaryngology service (mostly aged 12-21 years) and the control group comprised patients from a general otolaryngology service (mostly aged 18-25 years). Interventions: Data on patient-reported opioid consumption and outcomes were collected via a survey on postoperative day 14. Based on opioid consumption among pediatric otolaryngology patients before the intervention, the default number of opioid doses was decreased from 30 to 12 in a tonsillectomy order set. This change occurred only for pediatric otolaryngology patients. Main Outcomes and Measures: Proportion of patients with 12 doses in the discharge opioid prescription, number of doses in this prescription, and refills and pain-related visits within 2 weeks of surgery. In a secondary analysis of patients completing the postoperative survey, patient-reported opioid consumption, pain control, sleep disturbance, anxiety, and depression were assessed. Linear or log-linear difference-in-differences models were fitted, adjusting for patients' demographic characteristics and presence of a mental health or substance use disorder. Results: The study included 237 patients (147 female patients [62.0%]; mean [SD] age, 17.3 [3.6] years). Among 131 pediatric otolaryngology patients, 1 of 70 (1.4%) in the preintervention period and 27 of 61 (44.3%) in the postintervention period had 12 doses in the discharge opioid prescription (differential change, 45.5 percentage points; 95% CI, 32.2-58.8 percentage points). Among pediatric otolaryngology patients, the mean (SD) number of doses prescribed in the preintervention period was 22.3 (7.4) and in the postintervention period was 16.1 (6.5) (differential percentage change, -29.2%; 95% CI, -43.2% to -11.7%). The intervention was not associated with changes in refills or pain-related visits. The secondary analysis included 150 patients. The intervention was not associated with changes in patient-reported outcomes except for a 3.5-point (95% CI, 1.5-5.5 points) differential increase in a sleep disturbance score that ranged from 4 to 20, with higher scores indicating poorer sleep quality. Conclusions and Relevance: This nonrandomized clinical trial suggests that evidence-based default dosing settings may decrease perioperative opioid prescribing among adolescents and young adults undergoing tonsillectomy, without compromising analgesia. Trial Registration: ClinicalTrials.gov Identifier: NCT04066829.

Association Between Primary Care Practice Telehealth Use and Acute Care Visits for Ambulatory Care-Sensitive Conditions During COVID-19.

Importance: During the COVID-19 pandemic, many primary care practices adopted telehealth in place of in-person care to preserve access to care for patients with acute and chronic conditions. The extent to which this change was associated with their rates of acute care visits (ie, emergency department visits and hospitalizations) for these conditions is unknown. Objective: To examine whether a primary care practice's level of telehealth use is associated with a change in their rate of acute care visits for ambulatory care-sensitive conditions (ACSC visits). Design, Setting, and Participants: This retrospective cohort analysis used a difference-in-differences study design to analyze insurance claims data from 4038 Michigan primary care practices from January 1, 2019, to September 30, 2020. Exposures: Low, medium, or high tertile of practice-level telehealth use based on the rate of telehealth visits from March 1 to August 31, 2020, compared with prepandemic visit volumes. Main Outcomes and Measures: Risk-adjusted ACSC visit rates before (June to September 2019) and after (June to September 2020) the start of the COVID-19 pandemic, reported as an annualized average marginal effect. The study examined overall, acute, and chronic ACSC visits separately and controlled for practice size, in-person visit volume, zip code-level attributes, and patient characteristics. Results: A total of nearly 1.5 million beneficiaries (53% female; mean [SD] age, 40 [22] years) were attributed to 4038 primary care practices. Compared with 2019 visit volumes, median telehealth use was 0.4% for the low telehealth tertile, 14.7% for the medium telehealth tertile, and 39.0% for the high telehealth tertile. The number of ACSC visits decreased in all tertiles, with adjusted rates changing from 24.3 to 14.9 per 1000 patients per year (low), 23.9 to 15.3 per 1000 patients per year (medium), and 27.5 to 20.2 per 1000 patients per year (high). In difference-in-differences analysis, high telehealth use was associated with a higher ACSC visit rate (2.10 more visits per 1000 patients per year; 95% CI, 0.22-3.97) compared with low telehealth practices; practices in the middle tertile did not differ significantly from the low tertile. No difference was found in ACSC visits across tertiles when acute and chronic ACSC visits were examined separately. Conclusions and Relevance: In this cohort study that used a difference-in-differences analysis, the association between practice-level telehealth use and ACSC visits was mixed. High telehealth use was associated with a slightly higher overall ACSC visit rate than low telehealth practices. The association of telehealth with downstream care use should be closely monitored going forward.

Telehealth Use Before and During the COVID-19 Pandemic Among Children with Sickle Cell Anemia.

Introduction: Sickle cell anemia (SCA) is a genetic condition that predominantly affects minority populations in the United States. A lack of access to care is strongly associated with poor outcomes and quality of care among children and adolescents with SCA. The use of telehealth, which has rapidly expanded during the COVID-19 pandemic, has been shown to improve access to care for many conditions. However, the adoption of telehealth among children and adolescents with SCA is unknown. Methods: We identified children 1-17 years old with SCA continuously enrolled in Michigan Medicaid from January 2019 to December 2020. The number of in-person and telehealth outpatient visits (both urgent and routine) were summarized prepandemic (January 2019-February 2020) and during the pandemic (March 2020-December 2020); National Provider Identifier was used to identify provider specialty for telehealth visits. Results: The study population comprised 493 children with SCA with a mean age of 8.7 (±4.9) years at study entry. Prepandemic, there were 4,367 outpatient visits; 4,348 (99.6%) were in-person and 19 (0.4%) were telehealth. During the pandemic, there were 2,307 outpatient visits; 2,059 (89.3%) were in-person and 248 (10.7%) were telehealth. Telehealth visits peaked in April 2020 and declined thereafter. The majority of telehealth visits were to hematology (49%), followed by adult subspecialists (27%) and pediatrics/family medicine (14%). Discussion/Conclusions: While the overall number of outpatient visits declined during the initial months of the pandemic compared with 2019, use of telehealth rapidly increased among children and adolescents with SCA. Additional research is needed to understand patient and provider preferences for telehealth and the roles that federal and state policies can play in facilitating telehealth adoption among children and adolescents with SCA.

Predictors of Audio-Only Versus Video Telehealth Visits During the COVID-19 Pandemic.

BACKGROUND: Most health insurance organizations reimbursed both video and audio-only (i.e., phone) visits during the COVID-19 pandemic, but may discontinue phone visit coverage after the pandemic. The impact of discontinuing phone visit coverage on various patient subgroups is uncertain. OBJECTIVE: Identify patient subgroups that are more probable to access telehealth through phone versus video. DESIGN: Retrospective cohort. PATIENTS: All patients at a U.S. academic medical center who had an outpatient visit that was eligible for telehealth from April through June 2020. MAIN MEASURES: The marginal and cumulative effect of patient demographic, socioeconomic, and geographic characteristics on the probability of using video versus phone visits. KEY RESULTS: A total of 104,204 patients had at least one telehealth visit and 45.4% received care through phone visits only. Patient characteristics associated with lower probability of using video visits included age (average marginal effect [AME] -6.9% for every 10 years of age increase, 95%CI -7.8, -4.5), African-American (AME -10.2%, 95%CI -11.4, -7.6), need an interpreter (AME -19.3%, 95%CI -21.8, -14.4), Medicaid as primary insurance (AME -12.1%, 95%CI -13.7, -9.0), and live in a zip code with low broadband access (AME -7.2%, 95%CI -8.1, -4.8). Most patients had more than one factor which further reduced their probability of using video visits. CONCLUSIONS: Patients who are older, are African-American, require an interpreter, use Medicaid, and live in areas with low broadband access are less likely to use video visits as compared to phone. Post-pandemic policies that eliminate insurance coverage for phone visits may decrease telehealth access for patients who have one or more of these characteristics.

Association Between Receipt of Overlapping Opioid and Benzodiazepine Prescriptions From Multiple Prescribers and Overdose Risk.

Importance: The receipt of overlapping opioid and benzodiazepine prescriptions is associated with increased overdose risk. It is unknown whether this increase in risk varies when overlapping prescriptions are written by multiple prescribers vs 1 prescriber. Objective: To evaluate the association between receipt of overlapping opioid and benzodiazepine prescriptions from multiple prescribers and overdose risk. Design, Setting, and Participants: This cohort study was conducted using 2017 to 2018 claims from the Optum deidentified Clinformatics Data Mart. Participants were patients with private insurance or Medicare Advantage aged 12 years or older with overlapping opioid and benzodiazepine prescriptions. Data were analyzed from March through November 2020. Exposures: For each patient, person-days on which opioid and benzodiazepine prescriptions overlapped were identified. The exposure was whether these prescriptions were written by multiple prescribers vs 1 prescriber. Main Outcomes and Measures: The outcome was a treated overdose, defined as the occurrence of 1 or more claims containing a diagnosis code for opioid or benzodiazepine poisoning on a person-day of opioid-benzodiazepine overlap. The association between exposure and outcome at the person-day level was estimated using logistic regression, controlling for opioid and benzodiazepine prescribing patterns, demographics, and comorbidities. The average marginal effect (AME) of the exposure, defined as the absolute difference in the probability of a treated overdose if all person-days of overlap involved prescriptions from multiple prescribers vs 1 prescriber, was calculated. Results: Among 529 053 patients, the mean (SD) age was 61.2 (15.6) years and 350 857 (66.3%) were female patients. Mean (SD) follow-up was 198.7 (249.8) days. During follow-up, overdose occurred on 1 or more person-days of opioid-benzodiazepine overlap for 2288 patients (0.4%, or 1 in 231 patients). There were 52 989 316 person-days of opioid-benzodiazepine overlap. Among 19 895 457 person-days (37.5%) involving prescriptions from multiple prescribers, there were 1390 overdoses (7.0 per 100 000 person-days), and among 33 093 859 person-days (62.5%) involving prescriptions from 1 prescriber, there were 1302 overdoses (3.9 per 100 000 person-days). Overdose risk was increased 1.8-fold (95% CI, 1.6-1.9) on person-days of overlap involving prescriptions from multiple prescribers vs 1 prescriber. The association between multiple prescribers and increased risk of overdose persisted in adjusted analyses (adjusted odds ratio, 1.20; 95% CI, 1.10-1.31; AME, 0.91 per 100 000 person-days of overlap; 95% CI, 0.46-1.37). Conclusions and Relevance: This study found that among patients already at increased risk of overdose owing to concurrent treatment with opioids and benzodiazepines, overdose risk was increased further when multiple prescribers were responsible for this treatment regimen compared with 1 prescriber. This increased risk was not fully accounted for by differences in prescribing patterns, demographics, or comorbidities. This finding suggests that other factors, such as poor care coordination, may be associated with the increase in risk.

Direct-To-Consumer Telemedicine Visits For Acute Respiratory Infections Linked To More Downstream Visits.

Use of direct-to-consumer telemedicine-on-demand virtual care for minor medical issues-is growing rapidly. Although it may yield immediate savings by diverting health care from higher-cost settings, these savings could be countered if direct-to-consumer telemedicine increases follow-up care and, therefore, episode costs. Comparing downstream care utilization data from a large, commercial payer for the period 2016-19, we found that patients with initial visits for acute respiratory infection were more likely to obtain follow-up care within seven days after direct-to-consumer telemedicine visits (10.3 percent) than after in-person visits (5.9 percent). In both settings approximately 90 percent of patients did not obtain additional care. The telemedicine cohort had fewer (0.5 percent versus 0.6 percent) emergency department visits-a small but statistically significant difference-but more subsequent office, urgent care, and telemedicine visits. Our findings suggest that potential savings from shifting initial care to a direct-to-consumer telemedicine setting should be balanced against the potential for higher spending on downstream care.

Pre-existing Antineuraminidase Antibodies Are Associated With Shortened Duration of Influenza A(H1N1)pdm Virus Shedding and Illness in Naturally Infected Adults.

BACKGROUND: Influenza causes a substantial burden worldwide, and current seasonal influenza vaccine has suboptimal effectiveness. To develop better, more broadly protective vaccines, a more thorough understanding is needed of how antibodies that target the influenza virus surface antigens, hemagglutinin (HA) (including head and stalk regions) and neuraminidase (NA), impact influenza illness and virus transmission. METHODS: We used a case-ascertained, community-based study of household influenza virus transmission set in Managua, Nicaragua. Using data from 170 reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed influenza virus A(H1N1)pdm infections and 45 household members with serologically confirmed infection, we examined the association of pre-existing NA, hemagglutination inhibiting, and HA stalk antibody levels and influenza viral shedding and disease duration using accelerated failure time models. RESULTS: Among RT-PCR-confirmed infections in adults, pre-existing anti-NA antibody levels ≥40 were associated with a 69% (95% confidence interval [CI], 34-85%) shortened shedding duration (mean, 1.0 vs 3.2 days). Neuraminidase antibody levels ≥80 were associated with further shortened shedding and significantly shortened symptom duration (influenza-like illness, 82%; 95% CI, 39-95%). Among RT-PCR-confirmed infections in children, hemagglutination inhibition titers ≥1:20 were associated with a 32% (95% CI, 13-47%) shortened shedding duration (mean, 3.9 vs 6.0 days). CONCLUSIONS: Our results suggest that anti-NA antibodies play a large role in reducing influenza illness duration in adults and may impact transmission, most clearly among adults. Neuraminidase should be considered as an additional target in next-generation influenza virus vaccine development.We found that antibodies against neuraminidase were associated with significantly shortened viral shedding, and among adults they were also associated with shortened symptom duration. These results support neuraminidase as a potential target of next-generation influenza virus vaccines.

Prevalence of Mental Health Disorders Among Adults With Cerebral Palsy: A Cross-sectional Analysis.

Background: Persons with cerebral palsy (CP) have an increased risk for secondary chronic conditions during childhood, including mental health disorders. However, little is known about how these disorders affect adults with CP. Objective: To determine the prevalence of mental health disorders among adults with CP compared with those without CP. Design: Cross-sectional. Setting: 2016 Optum Clinformatics Data Mart. Patients: 8.7 million adults (including 7348 adults with CP). Measurements: Other neurodevelopmental comorbid conditions (intellectual disabilities, autism spectrum disorders, epilepsy) and 37 mental health disorders (as 6 categories) were identified on the basis of diagnosis codes. Direct age-standardized prevalence of the mental health disorder categories was estimated by sex for adults with CP alone, adults with CP and neurodevelopmental disorders, and adults without CP. Results: Men with CP alone had higher age-standardized prevalence than men without CP for schizophrenic disorders (2.8% [95% CI, 2.2% to 3.4%] vs. 0.7%), mood affective disorders (19.5% [CI, 18.0% to 21.0%] vs. 8.1%), anxiety disorders (19.5% [CI, 18.0% to 21.0%] vs. 11.1%), disorders of adult personality and behavior (1.2% [CI, 0.8% to 1.6%] vs. 0.3%), and alcohol- and opioid-related disorders (4.7% [CI, 3.9% to 5.5%] vs. 3.0%). The same pattern was observed for women. Compared with adults with CP alone, those with CP and neurodevelopmental disorders had similar or higher age-standardized prevalence of the 6 mental health disorder categories, except for the lower prevalence of alcohol- and opioid-related disorders in men. Limitations: Single claims code was used to define the cohort of interest. Information on the severity of CP was not available. Conclusion: Compared with adults without CP, those with CP have an elevated prevalence of mental health disorders, some of which may be more pronounced in patients with comorbid neurodevelopmental disorders. Primary Funding Source: National Institute on Disability, Independent Living, and Rehabilitation Research.

Prevalence of high-burden medical conditions and health care resource utilization and costs among adults with cerebral palsy.

Purpose: Individuals with cerebral palsy (CP) are susceptible to early development of high-burden medical conditions, which may place a considerable strain on health care resources. However, little is known about the prevalence of high-burden medical conditions or health care resource utilization among adults with CP. The purpose of this study was to determine the prevalence of high-burden medical conditions and health care resource utilization and costs among adults with CP, as compared to adults without CP. Patients and methods: Cross-sectional data from the 2016 Optum Clinformatics® Data Mart, a de-identified nationwide claims database of beneficiaries from a single private payer in the US. ICD-10-CM diagnosis codes were used to identify all medical conditions among beneficiaries with and without CP who were between 18 and 64 years of age. Medical and outpatient pharmacy claims were used to identify annual all-cause health care resource utilization and health care costs as standardized reimbursement and patient out-of-pocket costs. Results: Adults with CP (n=5,555) had higher prevalence and odds of all medical conditions compared to adults without CP (OR=1.3-5.8; all P<0.05), except cancer (OR=1.1; 95% CI=0.9-1.3). Adults with CP had greater annual mean counts of all health care service types (eg, inpatient, emergency department) compared to adults without CP (all P<0.01). Adults with CP had higher unadjusted standardized reimbursement (mean difference=$16,288; cost ratio [CR]=3.0; 95% CI=2.9-3.1) and patient out-of-pocket (mean difference=$778; CR=1.7; 95% CI=1.6-1.7) costs compared to adults without CP. After adjusting for all prevalent medical conditions, adults with CP still had higher standardized reimbursement (CR=2.5; 95% CI=2.5-2.6) and patient out-of-pocket (CR=1.8; 95% CI=1.7-1.8) costs. Conclusion: Adults with CP have a higher prevalence of high-burden medical conditions, health care resource utilization, and health care costs compared to adults without CP. Study findings suggest the need for earlier screening strategies and preventive medical services to quell the disease and economic burden attributable to adults with CP.

The respiratory microbiota: associations with influenza symptomatology and viral shedding.

PURPOSE: Manifestations of infection and the degree of influenza virus vary. We hypothesized that the nose/throat microbiota modifies the duration of influenza symptoms and viral shedding. Exploring these relationships may help identify additional methods for reducing influenza severity and transmission. METHODS: Using a household transmission study in Nicaragua, we identified secondary cases of influenza virus infection, defined as contacts with detectable virus or a greater than 4-fold change in hemagglutinin inhibition antibody titer. We characterized the nose/throat microbiota of secondary cases before infection and explored whether the duration of symptoms and shedding differed by bacterial community characteristics. RESULTS: Among 124 secondary cases of influenza, higher bacterial community diversity before infection was associated with longer shedding duration (Shannon acceleration factor [AF]: 1.61, 95% confidence interval [CI]: 1.24, 2.10) and earlier time to infection (Shannon AF: 0.72, 95% CI: 0.53, 0.97; Chao1 AF: 0.992, 95% CI: 0.986, 0.998). Neisseria and multiple other oligotypes were significantly associated with symptom and shedding durations and time to infection. CONCLUSIONS: The nose/throat microbiota before influenza virus infection was associated with influenza symptoms and shedding durations. Further studies are needed to determine if the nose/throat microbiota is a viable target for reducing influenza symptoms and transmission.

SPX4 Acts on PHR1-Dependent and -Independent Regulation of Shoot Phosphorus Status in Arabidopsis.

Phosphorus (P) is an essential macronutrient for all living organisms and limits plant growth. Four proteins comprising a single SYG1/Pho81/XPR1 (SPX) domain, SPX1 to SPX4, are putative phosphate-dependent inhibitors of Arabidopsis (Arabidopsis thaliana) PHOSPHATE STARVATION RESPONSE1 (PHR1), the master transcriptional activator of phosphate starvation responses. This work demonstrated that SPX4 functions as a negative regulator not only of PHR1-dependent but also of PHR1-independent responses in P-replete plants. Transcriptomes of P-limited spx4 revealed that, unlike SPX1 and SPX2, SPX4 modulates the shoot phosphate starvation response but not short-term recovery after phosphate resupply. In roots, transcriptional regulation of P status is SPX4 independent. Genes misregulated in spx4 shoots intersect with both PHR1-dependent and PHOSPHATE2-dependent signaling networks associated with plant development, senescence, and ion/metabolite transport. Gene regulatory network analyses suggested that SPX4 interacts with transcription factors other than PHR1, such as SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 and ARABIDOPSIS NAC DOMAIN CONTAINING PROTEIN55, known regulators of shoot development. Transient expression studies in protoplasts indicated that PHR1 retention in the cytosol by SPX4 occurs in a dose- and P-status-dependent manner. Using a luciferase reporter in vivo, SPX4 expression kinetics and stability revealed that SPX4 is a short-lived protein with P-status-dependent turnover. SPX4 protein levels were quickly restored by phosphate resupply to P-limited plants. Unlike its monocot ortholog, AtSPX4 was not stabilized by the phosphate analog phosphite, implying that intracellular P status is sensed by its SPX domain via phosphate-rich metabolite signals.

Psychological morbidity and chronic disease among adults with nontraumatic spinal cord injuries: a cohort study of privately insured beneficiaries.

BACKGROUND: Individuals living with a spinal cord injury (SCI) are at heightened risk for a number of chronic health conditions such as secondary comorbidities that may develop or be influenced by the injury, the presence of impairment, and/or the process of aging. However, very little is known about the development of secondary comorbidities among individuals living with nontraumatic SCIs (NTSCIs). PURPOSE: The objective of this study was to compare the prevalence of psychological morbidities and chronic diseases among adults with and without NTSCIs. DESIGN: Cross-sectional cohort from a nationwide insurance claims database. METHODS: Privately insured beneficiaries were included if they had an ICD-9-CM diagnostic code for a NTSCI and accompanying diagnosis of paraplegia, tetraplegia, quadriplegia, or unspecified paralysis (n=10,006). Adults without SCIs were also included (n=779,545). Prevalence estimates of common psychological morbidities, chronic diseases, and multimorbidity (≥2 conditions) were compared. RESULTS: Adults with NTSCIs had a higher prevalence of adjustment reaction (11.4% vs 5.1%), anxiety disorders (23.7% vs 14.5%), depressive disorders (31.6% vs 9.6%), drug dependence (3.4% vs 0.8%), episodic mood disorders (15.9% vs 5.4%), central pain syndrome (1% vs 0%), psychogenic pain (1.9% vs 0.2%), dementia (5.2% vs 1.5%), and psychological multimorbidity (29.3% vs 11.6%), as compared to adults without SCIs. The adjusted odds of psychological multimorbidity were 1.86 (95% confidence interval: 1.76-2.00). Adults with NTSCIs also had a significantly higher prevalence of all chronic diseases and chronic disease multimorbidity (73.5% vs 18%), except HIV/AIDS. After propensity matching for age, education, race, sex, and the chronic diseases (n=7,419 matched pairs), there was still a higher prevalence of adjustment reaction (9.2% vs 5.4%), depressive symptoms (23.5% vs 16.0%), central pain syndrome (1% vs 0%), psychogenic pain (1.5% vs 0.3%), and psychological multimorbidity (20.2% vs 17.4%) among adults with NTSCIs. CONCLUSIONS: Adults with NTSCIs have a significantly increased prevalence of psychological morbidities, chronic disease, and multimorbidity, as compared to adults without SCIs. Efforts are needed to facilitate the development of improved clinical screening algorithms and early interventions to reduce risk of disease onset/progression in this higher risk population.

Novel correlates of protection against pandemic H1N1 influenza A virus infection.

Influenza viruses remain a severe threat to human health, causing up to 650,000 deaths annually1,2. Seasonal influenza virus vaccines can prevent infection, but are rendered ineffective by antigenic drift. To provide improved protection from infection, novel influenza virus vaccines that target the conserved epitopes of influenza viruses, specifically those in the hemagglutinin stalk and neuraminidase, are currently being developed3. Antibodies against the hemagglutinin stalk confer protection in animal studies4-6. However, no data exist on natural infections in humans, and these antibodies do not show activity in the hemagglutination inhibition assay, the hemagglutination inhibition titer being the current correlate of protection against influenza virus infection7-9. While previous studies have investigated the protective effect of cellular immune responses and neuraminidase-inhibiting antibodies, additional serological correlates of protection from infection could aid the development of broadly protective or universal influenza virus vaccines10-13. To address this gap, we performed a household transmission study to identify alternative correlates of protection from infection and disease in naturally exposed individuals. Using this study, we determined 50% protective titers and levels for hemagglutination inhibition, full-length hemagglutinin, neuraminidase and hemagglutinin stalk-specific antibodies. Further, we found that hemagglutinin stalk antibodies independently correlated with protection from influenza virus infection.

The respiratory microbiome and susceptibility to influenza virus infection.

Influenza is a major cause of morbidity and mortality worldwide. However, vaccine effectiveness has been low to moderate in recent years and vaccine coverage remains low, especially in low- and middle-income countries. Supplementary methods of prevention should be explored to reduce the high burden of influenza. A potential target is the respiratory tract microbiome, complex microbial communities which envelop the respiratory epithelium and play an important role in shaping host immunity. Using a household transmission study, we examined whether the nose/throat microbiota was associated with influenza susceptibility among participants exposed to influenza virus in the household. Further, we characterized changes in the nose/throat microbiota to explore whether community stability was influenced by influenza virus infection. Using a generalized linear mixed effects model, we found a nasal/oropharyngeal community state type (CST) associated with decreased susceptibility to influenza. The CST was rare and transitory among young children but a prevalent and stable CST among adults. Using boosting and linear mixed effects models, we found associations between the nose/throat microbiota and influenza also existed at the taxa level, specifically with the relative abundance of Alloprevotella, Prevotella, and Bacteroides oligotypes. We found high rates of change between bacterial community states among both secondary cases and household contacts who were not infected during follow up. Further work is needed to separate the effect of influenza virus infection from the considerable short-term changes that occur even in the absence of virus. Lastly, age was strongly associated with susceptibility to influenza and the nose/throat bacterial community structure. Although additional studies are needed to determine causality, our results suggest the nose/throat microbiome may be a potential target for reducing the burden of influenza.

Obesity Increases the Duration of Influenza A Virus Shedding in Adults.

Epidemiologic studies indicate that obesity increases the risk of severe complications and death from influenza virus infections, especially in elderly individuals. This work investigates the effect of obesity on the duration of viral shedding within household transmission studies in Managua, Nicaragua, over 3 seasons (2015-2017). Symptomatic obese adults were shown to shed influenza A virus 42% longer than nonobese adults (adjusted event time ratio [ETR], 1.42; 95% confidence interval [CI], 1.06-1.89); no association was observed with influenza B virus shedding duration. Even among paucisymptomatic and asymptomatic adults, obesity increased the influenza A shedding duration by 104% (adjusted ETR, 2.04; 95% CI, 1.35-3.09). These findings suggest that obesity may play an important role in influenza transmission.