Challenges and Solutions to Support Oncology Professionals Serving Underserved Populations With Cancer in the United States: Results From the ASCO Serving the Underserved Task Force.

PURPOSE: Little data exist regarding approaches to support oncology professionals who deliver cancer care for underserved populations. In response, ASCO developed the Serving the Underserved Task Force to learn from and support oncology professionals serving underserved populations. METHODS: The Task Force developed a 28-question survey to assess oncology professionals' experiences and strategies to support their work caring for underserved populations. The survey was deployed via an online link to 600 oncology professionals and assessed respondent and patient demographic characteristics, clinic-based processes to coordinate health-related social services, and strategies for professional society support and engagement. We used chi-square tests to evaluate whether there were associations between percent full-time equivalent (FTE) effort serving underserved populations (<50% FTE v ≥50% FTE) with responses. RESULTS: Of 462 respondents who completed the survey (77% response rate), 79 (17.1%) were Asian; 30 (6.5%) Black; 43 (9.3%) Hispanic or Latino/Latina; and 277 (60%) White. The majority (n = 366, 79.2%) had a medical doctor degree (MD). A total of 174 (37.7%) had <25% FTE, 151 (32.7%) had 25%-50% FTE, and 121 (26.2%) had ≥50% FTE effort serving underserved populations. Most best guessed patients' sociodemographic characteristics (n = 388; 84%), while 42 (9.2%) used data collected by the clinic. Social workers coordinated most health-related social services. However, in clinical settings with high proportions of underserved patients, there was greater reliance on nonclinical personnel, such as navigators (odds ratio [OR], 2.15 [95% CI, 1.07 to 4.33]) or no individual (OR, 2.55 [95% CI, 1.14 to 5.72]) for addressing mental health needs and greater reliance on physicians or advance practice practitioners (OR, 2.54 [95% CI, 1.11 to 5.81]) or no individual (OR, 1.91 [95% CI, 1.09 to 3.35]) for addressing childcare or eldercare needs compared with social workers. Prioritization of solutions, which did not differ by FTE effort serving underserved populations, included a return-on-investment model to support personnel, integrated health-related social needs screening, and collaboration with the professional society on advocacy and policy. CONCLUSION: The findings highlight crucial strategies that professional societies can implement to support oncology clinicians serving underserved populations with cancer.

A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons.

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for 'gain setting' of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.

Brain-wide correspondence of neuronal epigenomics and distant projections.

Single-cell analyses parse the brain's billions of neurons into thousands of 'cell-type' clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.

The effect of modality onset asynchrony and processing time on the recognition of text-supplemented speech.

This study examined the effect of modality onset asynchrony and response processing time for the recognition of text-supplemented speech. Speech and text were periodically interrupted by noise or black bars, respectively, to preserve 50% of the sentence and presented in unimodal and multimodal conditions. Sentence recognition and response errors were assessed for responses made simultaneous with the stimulus or after its presentation. Increased processing time allowed for the cognitive repair of initial response errors in working memory. Text-supplemented speech was best recognized with minimal temporal asynchrony. Overall, text supplementation facilitated the recognition of degraded speech when provided sufficient processing time.

Is it Feasible? A Quality Improvement Project to Integrate Complementary Therapy Into a Pain Management Program on a Transitional Care Unit.

BACKGROUND: The cost of pain to society is high, not only in dollars but in physical and emotional suffering. Undertreated pain in the geriatric population can lead to functional impairments and diminished quality of life. A transitional care unit (TCU) described having higher levels of moderate to severe pain than state and national levels in like facilities. OBJECTIVE: A team of university faculty and students, and staff members from the TCU developed a quality improvement project to examine the feasibility of integrating complementary therapies to treat pain into clinical practice. METHODS: The team integrated three evidence-based complementary therapies into staff workflow. RESULTS: The nursing and therapy staff reported minimal to no interruption to their workflow when patients used the complementary therapies. Staff expressed satisfaction with an expanded menu of pain management options. Patients reported statistically significant lower (p = 0.002) pain levels after using the complementary therapies and benefits beyond pain relief, including relaxation, stress reduction, and improved sleep. CONCLUSION: Adding complementary therapies to the pain management program was feasible and the patients had less pain along with other benefits when using the therapies with standard care. IMPLICATIONS FOR NURSING: Having additional methods for managing pain is beneficial and vital.

Single-cell and single-nucleus RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates, and humans.

Abundant evidence supports the presence of at least three distinct types of thalamocortical (TC) neurons in the primate dorsal lateral geniculate nucleus (dLGN) of the thalamus, the brain region that conveys visual information from the retina to the primary visual cortex (V1). Different types of TC neurons in mice, humans, and macaques have distinct morphologies, distinct connectivity patterns, and convey different aspects of visual information to the cortex. To investigate the molecular underpinnings of these cell types, and how these relate to differences in dLGN between human, macaque, and mice, we profiled gene expression in single nuclei and cells using RNA-sequencing. These efforts identified four distinct types of TC neurons in the primate dLGN: magnocellular (M) neurons, parvocellular (P) neurons, and two types of koniocellular (K) neurons. Despite extensively documented morphological and physiological differences between M and P neurons, we identified few genes with significant differential expression between transcriptomic cell types corresponding to these two neuronal populations. Likewise, the dominant feature of TC neurons of the adult mouse dLGN is high transcriptomic similarity, with an axis of heterogeneity that aligns with core vs. shell portions of mouse dLGN. Together, these data show that transcriptomic differences between principal cell types in the mature mammalian dLGN are subtle relative to the observed differences in morphology and cortical projection targets. Finally, alignment of transcriptome profiles across species highlights expanded diversity of GABAergic neurons in primate versus mouse dLGN and homologous types of TC neurons in primates that are distinct from TC neurons in mouse.

Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior.

The ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) contains ∼4,000 neurons that project to multiple targets and control innate social behaviors including aggression and mounting. However, the number of cell types in VMHvl and their relationship to connectivity and behavioral function are unknown. We performed single-cell RNA sequencing using two independent platforms-SMART-seq (∼4,500 neurons) and 10x (∼78,000 neurons)-and investigated correspondence between transcriptomic identity and axonal projections or behavioral activation, respectively. Canonical correlation analysis (CCA) identified 17 transcriptomic types (T-types), including several sexually dimorphic clusters, the majority of which were validated by seqFISH. Immediate early gene analysis identified T-types exhibiting preferential responses to intruder males versus females but only rare examples of behavior-specific activation. Unexpectedly, many VMHvl T-types comprise a mixed population of neurons with different projection target preferences. Overall our analysis revealed that, surprisingly, few VMHvl T-types exhibit a clear correspondence with behavior-specific activation and connectivity.

Shared and distinct transcriptomic cell types across neocortical areas.

The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. We define 133 transcriptomic cell types by deep, single-cell RNA sequencing. Nearly all types of GABA (γ-aminobutyric acid)-containing neurons are shared across both areas, whereas most types of glutamatergic neurons were found in one of the two areas. By combining single-cell RNA sequencing and retrograde labelling, we match transcriptomic types of glutamatergic neurons to their long-range projection specificity. Our study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct areas of the adult mouse cortex.

Distinct descending motor cortex pathways and their roles in movement.

Activity in the motor cortex predicts movements, seconds before they are initiated. This preparatory activity has been observed across cortical layers, including in descending pyramidal tract neurons in layer 5. A key question is how preparatory activity is maintained without causing movement, and is ultimately converted to a motor command to trigger appropriate movements. Here, using single-cell transcriptional profiling and axonal reconstructions, we identify two types of pyramidal tract neuron. Both types project to several targets in the basal ganglia and brainstem. One type projects to thalamic regions that connect back to motor cortex; populations of these neurons produced early preparatory activity that persisted until the movement was initiated. The second type projects to motor centres in the medulla and mainly produced late preparatory activity and motor commands. These results indicate that two types of motor cortex output neurons have specialized roles in motor control.

Integration of partial information for spoken and written sentence recognition by older listeners.

Older adults have difficulty understanding speech in challenging listening environments. Combining multisensory signals may facilitate speech recognition. This study measured recognition of interrupted spoken and written sentences by older adults for different preserved stimulus proportions. Unimodal performance was first examined when only interrupted text or speech stimuli were presented. Multimodal performance with concurrently presented text and speech stimuli was tested with delayed and simultaneous participant responses. Older listeners performed better in unimodal speech-only compared to text-only conditions across all proportions preserved. Performance was also better in delayed multimodal conditions. Comparison to a younger sample suggests age-related amodal processing declines.

Health service utilisation by people living with chronic non-cancer pain: findings from the Pain and Opioids IN Treatment (POINT) study.

Objective The aims of the present study were to describe the use, and barriers to the use, of non-medication pain therapies and to identify the demographic and clinical correlates of different non-opioid pain treatments. Methods The study was performed on a cohort (n=1514) of people prescribed pharmaceutical opioids for chronic non-cancer pain (CNCP). Participants reported lifetime and past month use of healthcare services, mental and physical health, pain characteristics, current oral morphine equivalent daily doses and financial and access barriers to healthcare services. Results Participants reported the use of non-opioid pain treatments, both before and after commencing opioid therapy. Services accessed most in the past month were complementary and alternative medicines (CAMs; 41%), physiotherapy (16%) and medical and/or pain specialists (15%). Higher opioid dose was associated with increased financial and access barriers to non-opioid treatment. Multivariate analyses indicated being younger, female and having private health insurance were the factors most commonly associated with accessing non-opioid treatments. Conclusions Patients on long-term opioid therapy report using multiple types of pain treatments. High rates of CAM use are concerning given limited evidence of efficacy for some therapies and the low-income status of most people with CNCP. Financial and insurance barriers highlight the importance of considering how different types of treatments are paid for and subsidised. What is known about the topic? Given concerns regarding long-term efficacy, adverse side-effects and risk of misuse and dependence, prescribing guidelines recommend caution in prescribing pharmaceutical opioids in cases of CNCP, typically advising a multidisciplinary approach to treatment. There is a range of evidence supporting different (non-drug) treatment approaches for CNCP to reduce pain severity and increase functioning. However, little is known about the non-opioid treatments used among those with CNCP and the demographic and clinical characteristics that may be associated with the use of different types of treatments. Understanding the use of non-drug therapy among people with CNCP is crucial given the potential to improve pain control for these patients. What does this paper add? The present study found that a wide range of non-opioid treatments was accessed by the study sample, both before and after commencing opioids, indicating that in this sample opioids were not the sole strategy used for pain management. The most common treatment (other than opioids) was CAM, reported by two-fifths of the sample. Having private health insurance was associated with increased use of non-opioid treatments for pain, highlighting the importance of considering how treatments are paid for and potential financial barriers to effective treatments. What are the implications for practitioners? Patients' beliefs and financial barriers may affect the uptake of different treatments. Many patients may be using complementary and alternative approaches with limited evidence to support their use, highlighting the need for clinicians to discuss with patients the range of prescribed and non-prescribed treatments they are accessing and to help them understand the benefits and risks of treatments that have not been tested sufficiently, or have inconsistent evidence, as to their efficacy in improving pain outcomes.

Improving the reliability of physician "report cards".

BACKGROUND: Performance measures are widely used to profile primary care physicians (PCPs) but their reliability is often limited by small sample sizes. We evaluated the reliability of individual PCP profiles and whether they can be improved by combining measures into composites or by profiling practice groups. METHODS: We performed a cross-sectional analysis of electronic health record data for patients with diabetes (DM), congestive heart failure (CHF), ischemic vascular disease (IVD), or eligible for preventive care services seen by a PCP within a large, integrated health care system between April 2009 and May 2010. We evaluated performance on 14 measures of DM care, 9 of CHF, 7 of IVD, and 4 of preventive care. RESULTS: There were 51,771 patients observed by 163 physicians in 17 clinics. Few PCPs (0%-60%) could be profiled with 80% reliability using single process or intermediate-outcome measures. Combining measures into single-disease composites improved reliability for DM and preventive care with 74.5% and 76.7% of PCPs having sufficient panel sizes, but composites remained unreliable for CHF and IVD. A total of 85.3% of PCPs could be reliably profiled using a single overall composite. Aggregating PCPs into practice groups (3 to 21 PCPs per group) did not improve reliability in most cases because of little between-group practice variation. CONCLUSIONS: Single measures rarely differentiate between individual PCPs or groups of PCPs reliably. Combining measures into single-disease or multidisease composites can improve reliability for some common conditions, but not all. Assessing PCP practice groups within a single health care system, rather than individual PCPs, did not substantially improve reliability.

Relationship between fish intake, n-3 fatty acids, mercury and risk markers of CHD (National Health and Nutrition Examination Survey 1999-2002).

BACKGROUND: Fish consumption has been shown to be inversely associated with CHD, which may be due to n-3 fatty acids. The n-3 fatty acids, EPA and DHA, are naturally found only in marine sources. Dietary intakes of methylmercury from certain fish have been hypothesized to increase the risk of CHD. OBJECTIVE: To investigate the relationship between 30 d fish frequency consumption (assessed by FFQ), total blood Hg concentrations and risk markers of CHD in women aged 16-49 years participating in the National Health and Nutrition Examination Survey 1999-2002. DESIGN: Multiple linear regression analyses were used to test (i) the relationships between 30 d fish frequency consumption and five CHD risk markers, i.e. HDL cholesterol (HDL-C), LDL cholesterol, total cholesterol, TAG and C-reactive protein (CRP); and (ii) if total blood Hg attenuated any associations between fish consumption and CHD risk markers in non-pregnant, non-diabetic females aged 16-49 years. RESULTS: Total 30 d fish frequency consumption was negatively associated with CRP (b = -0.10, 95 % CI -0.19, -0.02, P = 0.015) and positively associated with HDL-C (b = 1.40, 95 % CI 0.31, 2.50, P = 0.014). Adjustment for other risk factors did not significantly attenuate the associations. Despite the collinearity between fish and Hg, there is a protective association between fish intake and CHD risk factors. CONCLUSIONS: The levels of DHA + EPA and other nutrients in fish may be adequate to offset the hypothesized risks of heart disease related to ingesting Hg from fish.

Cross validation of multiple methods for measuring pyrethroid and pyrethrum insecticide metabolites in human urine.

The objective of our study was to compare three vastly different analytical methods for measuring urinary metabolites of pyrethroid and pyrethrum insecticides to determine whether they could produce comparable data and to determine if similar analytical characteristics of the methods could be obtained by a secondary laboratory. This study was conducted as a part of a series of validation studies undertaken by the German Research Foundation's Committee on the Standardization of Analytical Methods for Occupational and Environmental Medicine. We compared methods using different sample preparation methods (liquid-liquid extraction and solid-phase extraction with and without chemical derivatization) and different analytical detection methods (gas chromatography-mass spectrometry (single quadrupole), gas chromatography-high resolution mass spectrometry (magnetic sector) in both electron impact ionization and negative chemical ionization modes, and high-performance liquid chromatography-tandem mass spectrometry (triple quadrupole) with electrospray ionization). Our cross validation proved that similar analytical characteristics could be obtained with any combination of sample preparation/analytical detection method and that all methods produced comparable analytical results on unknown urine samples.

Fish consumption: recommendations versus advisories, can they be reconciled?

Consumption of at least two servings of fish per week is recommended by the American Heart Association (AHA) to achieve cardio-protective effects. However, some fish are contaminated with methylmercury, which may counteract the positive effect of the omega-3 fatty acids, and numerous governments have issued advisories for certain fish species. These mixed messages may be a source of confusion to the consumer and to the health professional. This paper reviews whether it is possible to follow the AHA recommendation for fish consumption while avoiding the risks associated with consuming mercury in amounts in excess of government thresholds.

Light promotes regeneration and functional recovery and alters the immune response after spinal cord injury.

BACKGROUND AND OBJECTIVES: Photobiomodulation (PBM) has been proposed as a potential therapy for spinal cord injury (SCI). We aimed to demonstrate that 810 nm light can penetrate deep into the body and promote neuronal regeneration and functional recovery. STUDY DESIGN/MATERIALS AND METHODS: Adult rats underwent a T9 dorsal hemisection, followed by treatment with an 810 nm, 150 mW diode laser (dosage = 1,589 J/cm2). Axonal regeneration and functional recovery were assessed using single and double label tract tracing and various locomotor tasks. The immune response within the spinal cord was also assessed. RESULTS: PBM, with 6% power penetration to the spinal cord depth, significantly increased axonal number and distance of regrowth (P < 0.001). PBM also returned aspects of function to baseline levels and significantly suppressed immune cell activation and cytokine/chemokine expression. CONCLUSION: Our results demonstrate that light, delivered transcutaneously, improves recovery after injury and suggests that light will be a useful treatment for human SCI.

A pilot study of the safety and efficacy of cholestin in treating HIV-related dyslipidemia.

OBJECTIVE: We collected preliminary safety and efficacy data on the effects of Cholestin, a statin-containing dietary supplement, in individuals with dsylipidemia related to human immunodeficiency virus. METHODS: Fourteen adults with dsylipidemia related to human immunodeficiency virus characterized by hypercholesterolemia, hypertriacylglycerolemia, or both participated in a randomized, double-blind, placebo-controlled pilot study in an infectious disease clinic based in an academic medical center. Participants were randomly assigned to receive 1.2 g of Cholestin twice daily (n = 7) or placebo (n = 7) for 8 wk. The main outcome measures were safety (hepatic function tests, plasma human immunodeficiency virus-1 RNA levels, CD4(+) cell counts, adverse effects) and efficacy (fasting serum cholesterol: total, high- and low-density lipoproteins, and fasting serum triacylglycerols). Safety and efficacy outcomes were evaluated at 2- and 8-wk intervals. RESULTS: Twelve participants (n = 6 per group) completed the 8-wk treatment protocol. After 8 wk of treatment with Cholestin, there were significant declines from baseline in mean (+/- standard error of the mean) fasting total cholesterol (-30.8 +/- 8.8 versus 7.7 +/- 5.6; P = 0.01) and low-density lipoprotein cholesterol (-32.2 +/- 7.2 versus 26.3 +/- 14.2; P = 0.01) versus placebo. Moreover, the decline in fasting total cholesterol was significant (-40.2 +/- 4.8 versus 2.8 +/- 11.9; P = 0.006) after 2 wk of therapy, at which time the low-density lipoprotein cholesterol approached significance (-30.2 +/- 7.4 versus 4.4 +/- 15.2; P = 0.068). High-density lipoprotein cholesterol and triacylglycerol levels did not change at either time point. No adverse effects were seen with Cholestin. CONCLUSIONS: Cholestin may safely lower total and low-density lipoprotein cholesterol in patients with dsylipidemia related to human immunodeficiency virus. Larger and longer-term trials of this approach are warranted.