A distinct, high-affinity, alkaline phosphatase facilitates occupation of P-depleted environments by marine picocyanobacteria.

Marine picocyanobacteria of the genera Prochlorococcus and Synechococcus, the two most abundant phototrophs on Earth, thrive in oligotrophic oceanic regions. While it is well known that specific lineages are exquisitely adapted to prevailing in situ light and temperature regimes, much less is known of the molecular machinery required to facilitate occupancy of these low-nutrient environments. Here, we describe a hitherto unknown alkaline phosphatase, Psip1, that has a substantially higher affinity for phosphomonoesters than other well-known phosphatases like PhoA, PhoX, or PhoD and is restricted to clade III Synechococcus and a subset of high light I-adapted Prochlorococcus strains, suggesting niche specificity. We demonstrate that Psip1 has undergone convergent evolution with PhoX, requiring both iron and calcium for activity and likely possessing identical key residues around the active site, despite generally very low sequence homology. Interrogation of metagenomes and transcriptomes from TARA oceans and an Atlantic Meridional transect shows that psip1 is abundant and highly expressed in picocyanobacterial populations from the Mediterranean Sea and north Atlantic gyre, regions well recognized to be phosphorus (P)-deplete. Together, this identifies psip1 as an important oligotrophy-specific gene for P recycling in these organisms. Furthermore, psip1 is not restricted to picocyanobacteria and is abundant and highly transcribed in some α-proteobacteria and eukaryotic algae, suggesting that such a high-affinity phosphatase is important across the microbial taxonomic world to occupy low-P environments.

EnteroBase in 2025: exploring the genomic epidemiology of bacterial pathogens.

This paper presents an update on the content, accessibility and analytical tools of the EnteroBase platform for web-based pathogen genome analysis. EnteroBase provides manually curated databases of genome sequence data and associated metadata from currently >1.1 million bacterial isolates, more recently including Streptococcus spp. and Mycobacterium tuberculosis, in addition to Salmonella,Escherichia/Shigella,Clostridioides,Vibrio,Helicobacter,YersiniaandMoraxella. We have implemented the genome-based detection of antimicrobial resistance determinants and the new bubble plot graphical tool for visualizing bacterial genomic population structures, based on pre-computed hierarchical clusters. Access to data and analysis tools is provided through an enhanced graphical user interface and a new application programming interface (RESTful API). EnteroBase is now being developed and operated by an international consortium, to accelerate the development of the platform and ensure the longevity of the resources built. EnteroBase can be accessed at https://enterobase.warwick.ac.uk as well as https://enterobase.dsmz.de.

Cluster headache in adults.

Cluster headache is characterised by attacks of very severe, unilateral headache lasting 15-180 minutes, up to eight times per day. The attacks are associated with cranial autonomic symptoms on the same side and a sense of agitation or restlessness First-line acute abortive treatments include intranasal or subcutaneous sumatriptan or high-flow oxygen. Neuromodulation may benefit some patients First-line preventive therapy is high-dose verapamil. Close monitoring is required for the adverse effect of arrhythmia There are several emerging therapies that have either proven efficacy, or possible benefit for cluster headache. They include drugs aimed at the calcitonin gene-related peptide.

Calcitonin gene related peptide in migraine: current therapeutics, future implications and potential off-target effects.

Migraine is the second largest cause of years lost to disability globally among all diseases, with a worldwide prevalence over 1 billion. Despite the global burden of migraine, few classes of therapeutics have been specifically developed to combat migraine. After 30 years of translational research, calcitonin gene-related peptide (CGRP) inhibitors have emerged as a promising new tool in the prevention of migraine. Like all new therapeutics; however, we have limited real-world experience and CGRP has several known systemic actions that warrant consideration. This article provides a narrative review of the evidence for CGRP antagonists and summarises the known and potential side effects that should be considered.

The scope and severity of white-nose syndrome on hibernating bats in North America.

Assessing the scope and severity of threats is necessary for evaluating impacts on populations to inform conservation planning. Quantitative threat assessment often requires monitoring programs that provide reliable data over relevant spatial and temporal scales, yet such programs can be difficult to justify until there is an apparent stressor. Leveraging efforts of wildlife management agencies to record winter counts of hibernating bats, we collated data for 5 species from over 200 sites across 27 U.S. states and 2 Canadian provinces from 1995 to 2018 to determine the impact of white-nose syndrome (WNS), a deadly disease of hibernating bats. We estimated declines of winter counts of bat colonies at sites where the invasive fungus that causes WNS (Pseudogymnoascus destructans) had been detected to assess the threat impact of WNS. Three species undergoing species status assessment by the U.S. Fish and Wildlife Service (Myotis septentrionalis, Myotis lucifugus, and Perimyotis subflavus) declined by more than 90%, which warrants classifying the severity of the WNS threat as extreme based on criteria used by NatureServe. The scope of the WNS threat as defined by NatureServe criteria was large (36% of Myotis lucifugus range) to pervasive (79% of Myotis septentrionalis range) for these species. Declines for 2 other species (Myotis sodalis and Eptesicus fuscus) were less severe but still qualified as moderate to serious based on NatureServe criteria. Data-sharing across jurisdictions provided a comprehensive evaluation of scope and severity of the threat of WNS and indicated regional differences that can inform response efforts at international, national, and state or provincial jurisdictions. We assessed the threat impact of an emerging infectious disease by uniting monitoring efforts across jurisdictional boundaries and demonstrated the importance of coordinated monitoring programs, such as the North American Bat Monitoring Program (NABat), for data-driven conservation assessments and planning.

Alcance y Severidad del Síndrome de Nariz Blanca en los Murciélagos Hibernando en América del Norte Resumen La evaluación del alcance y la severidad de las amenazas es necesaria para los análisis de impacto sobre las poblaciones que se usan para orientar a la planeación de la conservación. La evaluación cuantitativa de amenazas con frecuencia requiere de programas de monitoreo que proporcionen datos confiables en escalas espaciales y temporales, aunque dichos programas pueden ser difíciles de justificar hasta que exista un estresante aparente. Gracias a una movilización de esfuerzos de las agencias de manejo de fauna para registrar los conteos invernales de murciélagos hibernadores, recopilamos datos para cinco especies en más de 200 sitios a lo largos de 27 estados de EUA y dos provincias canadienses entre 1995 y 2018 para determinar el impacto del síndrome de nariz blanca (SNB), una enfermedad mortal de los murciélagos hibernadores. Estimamos declinaciones en los conteos invernales de las colonias de murciélagos en sitios en donde el hongo invasivo que ocasiona el SNB (Pseudogymnoascus destructans) había sido detectado para evaluar el impacto de amenaza del SNB. Tres especies que se encuentran bajo valoración por parte del Servicio de Pesca y Vida Silvestre de los EUA (Myotis septentrionalis, Myotis lucifugus y Perimyotis subflavus) tuvieron una declinación de más del 90%, lo que justifica la clasificación de la severidad de la amenaza del SNB como extrema con base en el criterio usado por NatureServe. El alcance de la amenaza del SNB definido por el criterio de NatureServe fue desde amplio (36% de la distribución de Myotis lucifugus) hasta dominante (79% de la distribución de Myotis septentrionalis) para estas especies. Las declinaciones de otras dos especies (Myotis sodalis y Eptesicus fuscus) fueron menos severas, pero de igual manera quedaron clasificadas desde moderada hasta seria con base en los criterios de NatureServe. El intercambio de datos entre las jurisdicciones proporcionó una evaluación completa del alcance y la severidad de la amenaza del SNB e indicó las diferencias regionales que pueden guiar a los esfuerzos de respuesta realizados en las jurisdicciones internacionales, nacionales, estatales o provinciales. Evaluamos el impacto de amenaza de una enfermedad infecciosa emergente mediante la combinación de los esfuerzos de monitoreo que sobrepasan fronteras jurisdiccionales y demostramos la importancia que tienen para la planeación y la evaluación basadas en datos de la conservación los programas de monitoreo coordinados, como el Programa de Monitoreo de los Murciélagos Norteamericanos (NABat).

Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic Properties.

The impact of tumour associated stroma on cancer metastasis is an emerging field. However, cancer associated genes in peritumoral adipose tissue (pAT) in human colon cancer have not been explored. The aim of this study was to identify differentially expressed genes (DEGs) associated with cancer pathways in mesenteric pAT compared with adjacent adipose tissue. In total, nine patients with colon cancer pathological stage T2/T4 were employed in this study. DEGs were identified in 6 patients employing Nanostring PanCancer Pathway Panel and pathway enrichment analyses were performed. Differential expression of the 5 most up-regulated and 2 down regulated genes was validated with qRT-PCR. Results showed collagen type I alpha 1 chain (COL1A1) p = 0.007; secreted frizzled related protein (SFRP2) p = 0.057; fibroblast growth factor 7 (FGF7) not significant (ns); phospholipase A2, group IIA (PLA2G2A) ns; nerve growth factor receptor (NGFR) ns; lymphoid enhancer binding factor 1 (LEF1) p = 0.03; cadherin 1, Type 1, E-cadherin (epithelial) (CDH1) 0.09. Results have highlighted down-regulation of the Wingless/Integrated (Wnt) pathway in mesenteric pAT compared to distal adipose tissue. Highly upregulated genes in mesenteric pAT were involved in extracellular matrix (ECM)-receptor interactions and focal adhesion. Highly down regulated genes were involved in the cell cycle. Immunohistochemistry revealed differential distribution of COL1A1 showing maximum levels in tumour tissue and gradually decreasing in distant adipose tissue. COL1A1 and down regulation of Wnt pathway may have a role in local invasion and distant metastasis. COL1A1 may represent a stromal prognostic biomarker and therapeutic target in colon cancer.

Inflammatory complications of CGRP monoclonal antibodies: a case series.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response. CASES: We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy. CONCLUSION: This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.

Progressive multifocal leukoencephalopathy secondary to hepatitis C virus infection-related T-cell lymphopenia.

Progressive multifocal leukoencephalopathy (PML) is an uncommon neurological condition known to occur in the setting of T-cell immune suppression. We report a case of hepatitis C virus (HCV) infection-related T-cell lymphopenia manifesting as PML. HCV treatment and transient viral suppression resulted in immunological recovery with clinical stabilisation.

Real-world effectiveness of onabotulinumtoxinA treatment for the prevention of headaches in adults with chronic migraine in Australia: a retrospective study.

BACKGROUND: OnabotulinumtoxinA (BOTOX®, Allergan plc, Dublin, Ireland) is approved for the preventive treatment of headaches in adult patients with chronic migraine (CM) in Australia by the country's reimbursement mechanism for medicines, the Pharmaceutical Benefits Scheme (PBS). To our knowledge, this study represents the first focused report evaluating real-world evidence of onabotulinumtoxinA treatment via the PBS in Australian clinics. METHODS: This study reviewed the medical records of adults with inadequately controlled CM from 7 private neurology practices in Australia who, beginning in March 2014, received PBS-subsidized onabotulinumtoxinA per product labelling for the first time. The primary effectiveness measure was the percentage of patients achieving a response defined by 50% or greater reduction in headache days from baseline after 2 treatment cycles. Additional data were recorded in the case report form when available and included demographics, clinical characteristics, headache severity and frequency, Headache Impact Test (HIT-6) score, medication use, and days missed of work or study at baseline, after 2 treatment cycles, and at last follow-up. Differences in mean changes from baseline were evaluated with a 1-tailed t-test or Pearson's chi-squared test (p < 0.05). RESULTS: The study population included 211 patients with a mean (SD) of 25.2 (5.3) monthly headache days at baseline. In the primary outcome analysis, 74% of patients achieved a response, with a mean (SD) of 10.6 (7.9) headache days after 2 treatment cycles (p < 0.001). Secondary effectiveness outcomes included mean (SD) reductions in HIT-6 score of - 11.7 (9.8) and - 11.8 (12.2) after 2 treatment cycles (p < 0.001) and final follow-up (p < 0.001), respectively, and mean (SD) decreases in days per month of acute pain medication use of - 11.5 (7.6) after 2 treatment cycles (p < 0.001) and - 12.7 (8.1) at final follow-up (p < 0.001). CONCLUSION: This study provides additional clinical evidence for the consistent effectiveness of onabotulinumtoxinA for the treatment of CM in Australia. This effectiveness was made evident by reductions in migraine days, severe headache days, and HIT-6 scores from baseline.

Autoantibodies targeting TLR and SMAD pathways define new subgroups in systemic lupus erythematosus.

OBJECTIVES: The molecular targets of the vast majority of autoantibodies in systemic lupus erythematosus (SLE) are unknown. We set out to identify novel autoantibodies in SLE to improve diagnosis and identify subgroups of SLE individuals. METHODS: A baculovirus-insect cell expression system was used to create an advanced protein microarray with 1543 full-length human proteins expressed with a biotin carboxyl carrier protein (BCCP) folding tag, to enrich for correctly folded proteins. Sera from a discovery cohort of UK and US SLE individuals (n = 186) and age/ethnicity matched controls (n = 188) were assayed using the microarray to identify novel autoantibodies. Autoantibodies were validated in a second validation cohort (91 SLE, 92 controls) and a confounding rheumatic disease cohort (n = 92). RESULTS: We confirmed 68 novel proteins as autoantigens in SLE and 11 previous autoantigens in both cohorts (FDR<0.05). Using hierarchical clustering and principal component analysis, we observed four subgroups of SLE individuals associated with four corresponding clusters of functionally linked autoantigens. Two clusters of novel autoantigens revealed distinctive networks of interacting proteins: SMAD2, SMAD5 and proteins linked to TGF-ß signalling; and MyD88 and proteins involved in TLR signalling, apoptosis, NF-κB regulation and lymphocyte development. The autoantibody clusters were associated with different patterns of organ involvement (arthritis, pulmonary, renal and neurological). A panel of 26 autoantibodies, which accounted for four SLE clusters, showed improved diagnostic accuracy compared to conventional antinuclear antibody and anti-dsDNA antibody assays. CONCLUSIONS: These data suggest that the novel SLE autoantibody clusters may be of prognostic utility for predicting organ involvement in SLE patients and for stratifying SLE patients for specific therapies.

Long-term study of the efficacy and safety of OnabotulinumtoxinA for the prevention of chronic migraine: COMPEL study.

BACKGROUND: OnabotulinumtoxinA is approved for the prevention of headache in those with chronic migraine (CM); however, more clinical data on the risk-benefit profile for treatment beyond one year is desirable. METHODS: The Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL) Study ( ClinicalTrials.gov , NCT01516892) is an international, multicenter, open-label long-term prospective study. Adults with CM received 155 U of onabotulinumtoxinA (31 sites in a fixed-site, fixed-dose paradigm across 7 head/neck muscles) every 12 weeks (±7 days) for 9 treatment cycles (108 weeks). The primary outcome was headache day reductions at 108 weeks; secondary outcomes were headache day reductions at 60 weeks and change in the 6-item Headache Impact Test (HIT-6) score. Safety and tolerability were assessed by reviewing the frequency and nature of adverse events (AEs). AEs were determined at each visit through patient self-report, general non-directed and, for specific AEs, directed questioning, and physical examination. Subgroup analyses for safety and efficacy included, but were not limited to, patients with/without concomitant oral preventive treatment and acute medication overuse at baseline. RESULTS: Enrolled patients (N = 716) were 18-73 years old and most were female (n = 607, 84.8%). At baseline, patients reported an average 22.0 (SD = 4.8) headache days per month. 52.1% of patients (n = 373) completed the study. By 60 and 108 weeks, a significant reduction in headache days (- 9.2 days and - 10.7 days, respectively, P < 0.0001) was observed. Significant improvements (P < 0.0001) in HIT-6 scores (- 7.1 point change at week 108) were also demonstrated. 131 patients (18.3%) reported ≥1 treatment-emergent adverse events; most frequently reported was neck pain (n = 29, 4.1%). One patient reported a serious treatment-related adverse event (rash). No deaths were reported. CONCLUSIONS: The COMPEL Study provides additional clinical evidence for the consistency of the efficacy and for the long-term safety and tolerability of onabotulinumtoxinA for the prevention of headache in those with CM who have been treated with onabotulinumtoxinA every 12 weeks over 2 years (9 treatments) with the fixed-site, fixed-dose injection paradigm. TRIAL REGISTRATION: Trial registration number: NCT01516892 . Name of registry: clinicaltrials.gov . Date of registration: January 20 2012. Date of enrollment of first patient: December 2011.

The Association of Team-Specific Workload and Staffing with Odds of Burnout Among VA Primary Care Team Members.

BACKGROUND: Work-related burnout is common in primary care and is associated with worse patient safety, patient satisfaction, and employee mental health. Workload, staffing stability, and team completeness may be drivers of burnout. However, few studies have assessed these associations at the team level, and fewer still include members of the team beyond physicians. OBJECTIVE: To study the associations of burnout among primary care providers (PCPs), nurse care managers, clinical associates (MAs, LPNs), and administrative clerks with the staffing and workload on their teams. DESIGN: We conducted an individual-level cross-sectional analysis of survey and administrative data in 2014. PARTICIPANTS: Primary care personnel at VA clinics responding to a national survey. MAIN MEASURES: Burnout was measured with a validated single-item survey measure dichotomized to indicate the presence of burnout. The independent variables were survey measures of team staffing (having a fully staffed team, serving on multiple teams, and turnover on the team), and workload both from survey items (working extended hours), and administrative data (patient panel overcapacity and average panel comorbidity). KEY RESULTS: There were 4610 respondents (estimated response rate of 20.9%). The overall prevalence of burnout was 41%. In adjusted analyses, the strongest associations with burnout were having a fully staffed team (odds ratio [OR] = 0.55, 95% CI 0.47-0.65), having turnover on the team (OR = 1.67, 95% CI 1.43-1.94), and having patient panel overcapacity (OR = 1.19, 95% CI 1.01-1.40). The observed burnout prevalence was 30.1% lower (28.5% vs. 58.6%) for respondents working on fully staffed teams with no turnover and caring for a panel within capacity, relative to respondents in the inverse condition. CONCLUSIONS: Complete team staffing, turnover among team members, and panel overcapacity had strong, cumulative associations with burnout. Further research is needed to understand whether improvements in these factors would lower burnout.

Comparative tolerability of treatments for acute migraine: A network meta-analysis.

Introduction Migraine headache is a neurological disorder whose attacks are associated with nausea, vomiting, photophobia and phonophobia. Treatments for migraine aim to either prevent attacks before they have started or relieve attacks (abort) after onset of symptoms and range from complementary therapies to pharmacological interventions. A number of treatment-related adverse events such as somnolence, fatigue, and chest discomfort have previously been reported in association with triptans. The comparative tolerability of available agents for the abortive treatment of migraine attacks has not yet been systematically reviewed and quantified. Methods We performed a systematic literature review and Bayesian network meta-analysis for comparative tolerability of treatments for migraine. The literature search targeted all randomized controlled trials evaluating oral abortive treatments for acute migraine over a range of available doses in adults. The primary outcomes of interest were any adverse event, treatment-related adverse events, and serious adverse events. Secondary outcomes were fatigue, dizziness, chest discomfort, somnolence, nausea, and vomiting. Results Our search yielded 141 trials covering 15 distinct treatments. Of the triptans, sumatriptan, eletriptan, rizatriptan, zolmitriptan, and the combination treatment of sumatriptan and naproxen were associated with a statistically significant increase in odds of any adverse event or a treatment-related adverse event occurring compared with placebo. Of the non-triptans, only acetaminophen was associated with a statistically significant increase in odds of an adverse event occurring when compared with placebo. Overall, triptans were not associated with increased odds of serious adverse events occurring and the same was the case for non-triptans. For the secondary outcomes, with the exception of vomiting, all triptans except for almotriptan and frovatriptan were significantly associated with increased risk for all outcomes. Almotriptan was significantly associated with an increased risk of vomiting, whereas all other triptans yielded non-significant lower odds compared with placebo. Generally, the non-triptans were not associated with decreased tolerability for the secondary outcomes. Discussion In summary, triptans were associated with higher odds of any adverse event or a treatment-related adverse event occurring when compared to placebo and non-triptans. Non-significant results for non-triptans indicate that these treatments are comparable with one another and placebo regarding tolerability outcomes.

Sleep apnoea and the neurologist.

There is increasing awareness and interest in the complex and extensive inter-relationships between sleep disorders and neurological disorders. This review focuses on the clinical interactions between obstructive sleep apnoea and stroke, headaches, epilepsy, cognition and idiopathic Parkinson's disease. We highlight to the neurologist the importance of taking a sleep history and considering the diagnosis and treatment of obstructive sleep apnoea.

Sleep and chronic daily headache.

Sleep and headache have a complex and extensive interrelationship. This review focuses on the relationship between sleep and chronic daily headache, examining recent advances in the epidemiology and insights into possible mechanisms of this relationship as well as reviewing advances in treatment. There is a clear relationship between obstructive sleep apnoea (OSA) and snoring and morning headache, but the relationship between OSA and snoring and other primary headaches requires clarification. OSA and chronic migraine share both obesity and patent foramen ovale (PFO) as possible co-morbidities. Hypoxia does not clearly predispose to morning headache. Continuous positive airway pressure (CPAP) is an established treatment for OSA, and mixed results have been reported with regards to headache improvement with this treatment.

VA experience in implementing Patient-Centered Medical Home using a breakthrough series collaborative.

BACKGROUND: Veterans Health Administration (VHA) seeks to improve the delivery of patient-centered care. A Patient-Centered Medical Home (PCMH) Model, named Patient Aligned Care Team (PACT), was implemented to transform the VHA primary care delivery process. VHA used a collaborative learning model as a key approach to disseminate PACT concepts and changes. OBJECTIVE: To describe and examine VHA's experience disseminating PACT transformation using a Breakthrough Series Collaborative method. DESIGN: Observational study. PARTICIPANTS: Approximately 250-350 individuals from 141 teams participated in six face-to-face learning sessions across 21 months. MAIN MEASURES: 1) PACT Collaborative participant surveys; 2) Coach Assessment Scores and Plan-Do-Study-Act (PDSA) data; and 3) PACT Compass (national measures to assess PACT implementation within VA healthcare system). KEY RESULTS: A majority of the participants indicated that the PACT Collaborative was necessary to implement PACT. The number of PDSAs increased steadily during the Collaborative period; 93 % (n = 1,547) of PDSAs were successfully implemented. Teams successfully achieved over 80 % of their aims, which were highly correlated with PDSAs implemented (R(2) = 0.88). The most successful aims achieved were offering same-day appointments, increasing non-face-to-face care, and improving team communication. PACT Compass indicated an improvement after the Collaborative (p-value < .000), and providers observed differences in their care practice (p-value < 0.002). This positive impact may be due to the spread of the PACT Model through the PACT Collaborative, among other learning initiatives. CONCLUSIONS: For complex collaborative models such as PACT, more than three learning sessions may be required. As VHA continues to disseminate the PACT Model through primary care, into specialty/surgical care and beyond, the Collaborative Learning Model may continue to be an effective way to leverage a small number of faculty, coaches, and industrial engineers across an extremely large population.

Challenges facing primary care practices aiming to implement patient-centered medical homes.

BACKGROUND: While the potential of patient-centered medical homes (PCMH) is promising, little is known empirically about the frontline challenges that primary care (PC) leaders face before making the decision to implement PCMH, let alone in making it a reality. OBJECTIVE: Prior to the design and implementation of the Veterans Health Administration's (VA) national PCMH model--Patient Aligned Care Teams (PACT)--we identified the top challenges faced by PC directors and examined the organizational and area level factors that influenced those challenges. DESIGN AND PARTICIPANTS: A national cross-sectional key informant organizational survey was fielded to the census of PC directors at VA medical centers and large community-based outpatient clinics (final sample n = 229 sites). MAIN MEASURES: PC directors were asked to rate the degree to which they faced 48 management challenges in eight PCMH-related domains (access, preventive care, chronic diseases requiring care in PC, challenging medical conditions, mental health/substance abuse, special populations, PC coordination of care, and clinical informatics). Responses were dichotomized as moderately-to-extremely challenging versus somewhat-slightly-not at all challenging. Items were rank ordered; chi square or regression techniques were used to examine variations in facility size, type, urban/rural location, and region. KEY RESULTS: On average, VA PC directors reported 16 moderate-to-extreme challenges, and the top 20 challenges spanned all eight PCMH domains. Four of the top 20 challenges, including the top two challenges, were from the clinical informatics domain. Management of chronic non-malignant pain requiring opiate therapy was the third most reported challenge nationwide. Significant organizational and area level variations in reported challenges were found especially for care coordination. CONCLUSIONS: Better understanding of PC challenges ahead of PCMH implementation provides important context for strategic planning and redesign efforts. As a national healthcare system, the VA provides a unique opportunity to examine organizational and area determinants relevant to other PCMH models.

Elements of team-based care in a patient-centered medical home are associated with lower burnout among VA primary care employees.

BACKGROUND: A high proportion of the US primary care workforce reports burnout, which is associated with negative consequences for clinicians and patients. Many protective factors from burnout are characteristics of patient-centered medical home (PCMH) models, though even positive organizational transformation is often stressful. The existing literature on the effects of PCMH on burnout is limited, with most findings based on small-scale demonstration projects with data collected only among physicians, and the results are mixed. OBJECTIVE: To determine if components of PCMH related to team-based care were associated with lower burnout among primary care team members participating in a national medical home transformation, the VA Patient Aligned Care Team (PACT). DESIGN: Web-based, cross-sectional survey and administrative data from May 2012. PARTICIPANTS: A total of 4,539 VA primary care personnel from 588 VA primary care clinics. MAIN MEASURES: The dependent variable was burnout, and the independent variables were measures of team-based care: team functioning, time spent in huddles, team staffing, delegation of clinical responsibilities, working to top of competency, and collective self-efficacy. We also included administrative measures of workload and patient comorbidity. KEY RESULTS: Overall, 39 % of respondents reported burnout. Participatory decision making (OR 0.65, 95 % CI 0.57, 0.74) and having a fully staffed PACT (OR 0.79, 95 % CI 0.68, 0.93) were associated with lower burnout, while being assigned to a PACT (OR 1.46, 95 % CI 1.11, 1.93), spending time on work someone with less training could do (OR 1.29, 95 % CI 1.07, 1.57) and a stressful, fast-moving work environment (OR 4.33, 95 % CI 3.78, 4.96) were associated with higher burnout. Longer tenure and occupation were also correlated with burnout. CONCLUSIONS: Lower burnout may be achieved by medical home models that are appropriately staffed, emphasize participatory decision making, and increase the proportion of time team members spend working to the top of their competency level.

A non-inferiority clinical trial comparing probiotics and oral corticosteroids for the management of acute exacerbation of atopic dermatitis patients.

A prospective controlled pilot study on the feasibility of utilization of a probiotic mixture for management of acute exacerbation of atopic dermatitis (AD). Patients were allocated to either standard of care (SOC) therapy with tapering dose of steroids or a probiotic mixture over 3 weeks. After the 3-week intervention, patients on steroids achieved significantly higher clinical response rates and significantly deeper response as measured by the change in SCORAD score. No gut microbiome changes could be appreciated in either group after the treatment period. We could conclude that probiotics cannot replace SOC therapy for the management of acute exacerbation of AD.