Robust cross-cohort gut microbiome associations with COVID-19 severity.

Although many recent studies have examined associations between the gut microbiome and COVID-19 disease severity in individual patient cohorts, questions remain on the robustness across international cohorts of the biomarkers they reported. Here, we performed a meta-analysis of eight shotgun metagenomic studies of COVID-19 patients (comprising 1,023 stool samples) and 23 > 16S rRNA gene amplicon sequencing (16S) cohorts (2,415 total stool samples). We found that disease severity (as defined by the WHO clinical progression scale) was associated with taxonomic and functional microbiome differences. This alteration in gut microbiome configuration peaks at days 7-30 post diagnosis, after which the gut microbiome returns to a configuration that becomes more similar to that of healthy controls over time. Furthermore, we identified a core set of species that were consistently associated with disease severity across shotgun metagenomic and 16S cohorts, and whose abundance can accurately predict disease severity category of SARS-CoV-2 infected subjects, with Actinomyces oris abundance predicting population-level mortality rate of COVID-19. Additionally, we used relational diet-microbiome databases constructed from cohort studies to predict microbiota-targeted diet patterns that would modulate gut microbiota composition toward that of healthy controls. Finally, we demonstrated the association of disease severity with the composition of intestinal archaeal, fungal, viral, and parasitic communities. Collectively, this study has identified robust COVID-19 microbiome biomarkers, established accurate predictive models as a basis for clinical prognostic tests for disease severity, and proposed biomarker-targeted diets for managing COVID-19 infection.

Chemically Fueled Reinforcement of Polymer Hydrogels.

Carbodiimide-fueled anhydride bond formation has been used to enhance the mechanical properties of permanently crosslinked polymer networks, giving materials that exhibit transitions from soft gels to covalently reinforced gels, eventually returning to the original soft gels. Temporary changes in mechanical properties result from a transient network of anhydride crosslinks, which eventually dissipate by hydrolysis. Over an order of magnitude increase in the storage modulus is possible through carbodiimide fueling. The time-dependent mechanical properties can be modulated by the concentration of carbodiimide, temperature, and primary chain architecture. Because the materials remain rheological solids, new material functions such as temporally controlled adhesion and rewritable spatial patterns of mechanical properties have been realized.

A case management occupational health model to facilitate earlier return to work of NHS staff with common mental health disorders: a feasibility study.

BACKGROUND: The NHS is the biggest employer in the UK. Depression and anxiety are common reasons for sickness absence among staff. Evidence suggests that an intervention based on a case management model using a biopsychosocial approach could be cost-effective and lead to earlier return to work for staff with common mental health disorders. OBJECTIVE: The objective was to assess the feasibility and acceptability of conducting a trial of the clinical effectiveness and cost-effectiveness of an early occupational health referral and case management intervention to facilitate the return to work of NHS staff on sick leave with any common mental health disorder (e.g. depression or anxiety). DESIGN: A multicentre mixed-methods feasibility study with embedded process evaluation and economic analyses. The study comprised an updated systematic review, survey of care as usual, and development of an intervention in consultation with key stakeholders. Although this was not a randomised controlled trial, the study design comprised two arms where participants received either the intervention or care as usual. PARTICIPANTS: Participants were NHS staff on sick leave for 7 or more consecutive days but less than 90 consecutive days, with a common mental health disorder. INTERVENTION: The intervention involved early referral to occupational health combined with standardised work-focused case management. CONTROL/COMPARATOR: Participants in the control arm received care as usual. PRIMARY OUTCOME: The primary outcome was the feasibility and acceptability of the intervention, study processes (including methods of recruiting participants) and data collection tools to measure return to work, episodes of sickness absence, workability (a worker's functional ability to perform their job), occupational functioning, symptomatology and cost-effectiveness proposed for use in a main trial. RESULTS: Forty articles and two guidelines were included in an updated systematic review. A total of 49 of the 126 (39%) occupational health providers who were approached participated in a national survey of care as usual. Selected multidisciplinary stakeholders contributed to the development of the work-focused case management intervention (including a training workshop). Six NHS trusts (occupational health departments) agreed to take part in the study, although one trust withdrew prior to participant recruitment, citing staff shortages. At mixed intervention sites, participants were sequentially allocated to each arm, where possible. Approximately 1938 (3.9%) NHS staff from the participating sites were on sick leave with a common mental health disorder during the study period. Forty-two sick-listed NHS staff were screened for eligibility on receipt of occupational health management referrals. Twenty-four (57%) participants were consented: 11 (46%) received the case management intervention and 13 (54%) received care as usual. Follow-up data were collected from 11 out of 24 (46%) participants at 3 months and 10 out of 24 (42%) participants at 6 months. The case management intervention and case manager training were found to be acceptable and inexpensive to deliver. Possible contamination issues are likely in a future trial if participants are individually randomised at mixed intervention sites. HARMS: No adverse events were reported. LIMITATIONS: The method of identification and recruitment of eligible sick-listed staff was ineffective in practice because uptake of referral to occupational health was low, but a new targeted method has been devised. CONCLUSION: All study questions were addressed. Difficulties raising organisational awareness of the study coupled with a lack of change in occupational health referral practices by line managers affected the identification and recruitment of participants. Strategies to overcome these barriers in a main trial were identified. The case management intervention was fit for purpose and acceptable to deliver in the NHS. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14621901. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 12. See the NIHR Journals Library website for further project information.

Anxiety and depression are common causes of sickness absence in the NHS. This can harm patient care. Previous research has shown that offering early support to NHS staff on sick leave with a common mental health disorder is important to aid recovery and rehabilitation. However, it is not currently known how best to support staff in returning to work. The purpose of this research was to test the feasibility of a large-scale study to see if specially trained occupational health nurses would be effective in getting NHS staff with these problems back to work quicker. We reviewed the recent scientific literature and did a survey of NHS occupational health departments to find out what was currently offered to such staff. We developed a new work-focused case management intervention and trained six occupational health nurses to deliver it. We recruited 24 NHS staff who were on sick leave with a common mental health disorder (such as depression or anxiety) and allocated 11 to receive the new intervention and the rest to receive usual support. Participants were invited to complete three questionnaires and we collected information from the participating occupational health sites. We also interviewed participants, managers, human resource staff and occupational health nurses to find out what they thought about being involved in the study. We found that the new case management intervention had potential benefits. However, it would not be possible to run a trial to evaluate the intervention until a better way can be found to encourage the early referral of sick staff to occupational health.

Benefits of Cochlear Implantation for Single-Sided Deafness: Data From the House Clinic-University of Southern California-University of California, Los Angeles Clinical Trial.

OBJECTIVES: Cochlear implants (CIs) have been shown to benefit patients with single-sided deafness (SSD) in terms of tinnitus reduction, localization, speech understanding, and quality of life (QoL). While previous studies have shown cochlear implantation may benefit SSD patients, it is unclear which point of comparison is most relevant: baseline performance before implantation versus performance with normal-hearing (NH) ear after implantation. In this study, CI outcomes were assessed in SSD patients before and up to 6 mo postactivation. Benefits of cochlear implantation were assessed relative to binaural performance before implantation or relative to performance with the NH ear alone after implantation. DESIGN: Here, we report data for 10 patients who completed a longitudinal, prospective, Food and Drug Administration-approved study of cochlear implantation for SSD patients. All subjects had severe to profound unilateral hearing loss in one ear and normal hearing in the other ear. All patients were implanted with the MED-EL CONCERTO Flex 28 device. Speech understanding in quiet and in noise, localization, and tinnitus severity (with the CI on or off) were measured before implantation (baseline) and at 1, 3, 6 mo postactivation of the CI processor. Performance was measured with both ears (binaural), the CI ear alone, and the NH ear alone (the CI ear was plugged and muffed). Tinnitus severity, dizziness severity, and QoL were measured using questionnaires administered before implantation and 6 mo postactivation. RESULTS: Significant CI benefits were observed for tinnitus severity, localization, speech understanding, and QoL. The degree and time course of CI benefit depended on the outcome measure and the reference point. Relative to binaural baseline performance, significant and immediate (1 mo postactivation) CI benefits were observed for tinnitus severity and speech performance in noise, but localization did not significantly improve until 6 mo postactivation; questionnaire data showed significant improvement in QoL 6 mo postactivation. Relative to NH-only performance after implantation, significant and immediate benefits were observed for tinnitus severity and localization; binaural speech understanding in noise did not significantly improve during the 6-mo study period, due to variability in NH-only performance. There were no correlations between behavioral and questionnaire data, except between tinnitus visual analog scale scores at 6 mo postactivation and Tinnitus Functional Index scores at 6 mo postactivation. CONCLUSIONS: The present behavioral and subjective data suggest that SSD patients greatly benefit from cochlear implantation. However, to fully understand the degree and time course of CI benefit, the outcome measure and point of comparison should be considered. From a clinical perspective, binaural baseline performance is a relevant point of comparison. The lack of correlation between behavioral and questionnaire data suggest that represent independent measures of CI benefit for SSD patients.

Sharing is Caring: Minimizing the Disruption with Palliative Care.

There is an upward trend incidence of multiple chronic life-limiting conditions with a well-documented associated impact on patients and their caregivers. When patients approach the end of life, they are often faced with a challenging multidimensional burden while navigating a complex health care system. Patients and families/caregivers are faced with daily decisions, often with little or no frame of reference or medical knowledge. The "what, how, when, and where" puzzle during this challenging time can be overwhelming for patients and their families, and when clinicians do not contemplate this associated workload's impact on patients and caregivers' capacity for self-care, patients and caregivers scramble to find compensatory solutions, often putting their health care at lower priority. This consequently warrants the underlying importance of palliative care and integrating it into the patients' health care plans earlier. There is increasing evidence from recent trials that supported implementing national policies regarding the early integration of palliative care and its role in improving the quality of life, increasing survival, and supporting patients' and caregivers' values when making decisions about their health care while possibly minimizing the burden of illness. The mission of palliative care is to assess, anticipate, and alleviate the challenges and suffering for patients and their caregivers by providing well-constructed approaches to disease-related physical treatments as well as psychological, financial, and spiritual aspects. Communication among all participants (the patient, family/caregivers, and all involved health care professionals) ought to be timely, thorough, and patient-centric. Palliative medicine arguably represents an example of shared decision-making (SDM)-facilitating a patient-centered, informed decision-making through an empathic conversation that is supported by clinicians' expertise and the best available evidence that takes patients values and preferences into consideration. Palliative care teams often consider the burden placed on patients and their caregivers, thus treatment plans would be assessed and introduced into the patients' lives with reflection on the related workload and the potential capacity to take on those plans. Such an approach to pause-and-examine, understand-and-discuss, and assess-and-alleviate might provide a possible example of a health care system that is minimally disruptive to patients and their families. This is an opportunity to replace the information-filled encounter with a more constructive engagement and empowerment to all major stakeholders to participate-an axiom integral to palliative care. Using the best available evidence in caring for patients while enacting SDM, palliative care, primary care, and other subspecialty clinicians need to consider the significant workload and burden that comes with health care and thus explore pathways to minimize the disruption in patients and caregivers' lives. As we collaborate to end cancer and all other mobdeities, we a need a concurrent movement to transform this disease-centered, payer-driven health care era to a rather patient-entered, thoughtful, and minimally disruptive one will benefit patients and physicians alike.

The Neuropeptides of Ocular Immune Privilege, α-MSH and NPY, Suppress Phagosome Maturation in Macrophages.

The ocular microenvironment has evolutionarily adapted several mechanisms of immunosuppression to minimize the induction of inflammation. Neuropeptides produced by the retinal pigment epithelial cells regulate macrophage activity. Two neuropeptides, α-melanocyte-stimulating hormone (α -MSH) and neuropeptide Y (NPY), are constitutively expressed by the retinal pigment epithelial cells. Together these two neuropeptides induce anti-inflammatory cytokine production in endotoxin-stimulated macrophages and suppress phagocytosis of unopsonized bioparticles. These neuropeptides do not suppress the phagocytosis of opsonized bioparticles; however, they do suppress phagolysosome activation or formation. In this report, we studied the possibility that α-MSH with NPY suppress phagosome maturation within macrophages using opsonized OVA-coated magnetic beads to isolate and analyze the phagosomes. The magnetic bead-containing intercellular vesicles were isolated and assayed for Rab5, Rab7, LAMP1, Iad, and OVA. The macrophages cotreated with α-MSH and NPY were suppressed in Rab7 recruitment to the phagosome with suppression in LAMP1 expression but not in Iad expression. The results demonstrated that the α-MSH/NPY cotreatment suppressed phagosome maturation. In addition, the a-MSH/NPY-cotreated macrophages were suppressed in their ability to Ag stimulate CD4+ T cell proliferation. These results imply a potential mechanism of ocular immune privilege to divert Ag processing to prevent autoreactive effector T cells from binding their target cognate Ag within the ocular microenvironment.

Motivational interviewing in respiratory therapy: What do clinicians need to make it part of routine care? A qualitative study.

Motivational interviewing (MI) is a method for building motivation for behaviour change that has potential for use in respiratory contexts. There is a paucity of published research exploring the feasibility of this intervention from the clinicians' perspective. This study aimed to explore respiratory clinicians' views of MI: Is it perceived as useful? Could it be integrated into practice? What training would be required to make it part of routine care? Nine respiratory clinicians attended a one-day MI workshop and a semi-structured face-to-face interview two weeks later. All interviews were audio-recorded, transcribed verbatim and analysed with thematic analysis. Four main themes are presented-1) MI's suitability for use in respiratory contexts: participants saw potential in using MI to motivate their patients to engage with prescribed respiratory interventions, such as increased physical activity. Those who experimented with new skills post-workshop were encouraged by patient responsiveness and outcomes. 2) MI's relationship with routine clinical practice: some believed they already used elements of MI, but most participants felt MI was fundamentally 'different' to their normal style of working. 3) Implementation issues: additional time would need to be made available to enable an appropriate depth of conversation. 4) Training issues: Participants sensed the complexity of MI could make it difficult to learn and that it would take them time to become competent. On-going supervision was perceived as necessary. One key challenge identified was how to suppress behaviours that are antithetical to MI. These findings lend support to the feasibility of using MI in respiratory contexts such as pulmonary rehabilitation programmes, but highlight implementation and training issues that would need to be overcome. The insights have informed the development of another study, testing the effect of a tailored training package on MI skill, specifically for respiratory clinicians delivering pulmonary rehabilitation programmes.

Patient-reported distress and survival among patients receiving definitive radiation therapy.

OBJECTIVE: Patient-reported distress (PRD) has not been well assessed in association with survival after radiation therapy (RT). The aims of this study were to evaluate the association between PRD level and survival after definitive RT and to identify the main causes of distress in definitive RT patients. METHODS AND MATERIALS: A total of 678 consecutive patients receiving definitive RT at our institution from April 2012 through May 2015 were included. All patients answered a PRD questionnaire that contained 30 items related to possible causes of distress, which could be rated from 1 (no distress) to 5 (high distress). Additionally, patients were asked to rate their overall distress level from 0 (no distress) to 10 (extreme distress). This overall distress level was our primary patient-reported distress measure and was examined as a continuous variable and as a categorical variable with 3 PRD levels (low, 0-3 [n = 295]; moderate, 4-6 [n = 222]; and high, 7-10 [n = 161]). RESULTS: As a continuous variable in multivariable Cox regression analysis, a higher overall PRD level was associated with poorer survival after RT (hazard ratio [HR], 1.39; P = .004). As a categorical variable, compared with patients with low distress, survival was poorer for patients with moderate distress (HR, 1.62; P = .038) or high distress (HR, 1.49; P = .12), but the latter difference was not significant. When the moderate and high distress levels were combined, survival was significantly poorer compared with the low distress level (HR, 1.57; P = .034). The top 5 specific causes of distress that patients mentioned were "How I feel during treatment," "Fatigue," "Out-of-pocket medical costs," "Pain that affects my daily functioning," and "Sleep difficulties." CONCLUSIONS: PRD before or during RT is a prognostic factor associated with decreased survival. Distress screening guidelines and interventions should be implemented for patients receiving definitive RT.

Initial Results of a Safety and Feasibility Study of Auditory Brainstem Implantation in Congenitally Deaf Children.

OBJECTIVE: To determine the safety and feasibility of the auditory brainstem implant (ABI) in congenitally deaf children with cochlear aplasia and/or cochlear nerve deficiency. STUDY DESIGN: Phase I feasibility clinical trial of surgery in 10 children, ages 2 to 5 years, over a 3-year period. SETTING: Tertiary children's hospital and university-based pediatric speech/language/hearing center. INTERVENTION(S): ABI implantation and postsurgical programming. MAIN OUTCOME MEASURE(S): The primary outcome measure is the number and type of adverse events during ABI surgery and postsurgical follow-up, including behavioral mapping of the device. The secondary outcome measure is access to and early integration of sound. RESULTS: To date, nine children are enrolled. Five children have successfully undergone ABI surgery and postoperative behavioral programming. Three children were screen failures, and one child is currently undergoing candidacy evaluation. Expected adverse events have been documented in three of the five children who received the ABI. One child experienced a cerebral spinal fluid leak, which resolved with lumbar drainage. One child demonstrated vestibular side effects during device programming, which resolved by deactivating one electrode. One child experienced postoperative vomiting resulting in an abdominal radiograph. Four children have completed their 1-year follow-up and have speech detection thresholds of 30 to 35 dB HL. Scores on the IT-MAIS/MAIS range from 8 to 31 (out of a total of 40), and the children are demonstrating some ability to discriminate between closed-sets words that differ by number of syllables (pattern perception). CONCLUSION: ABI surgery and device activation seem to be safe and feasible in this preliminary cohort.

Is Birdsong More Like Speech or Music?

Music and speech share many acoustic cues but not all are equally important. For example, harmonic pitch is essential for music but not for speech. When birds communicate is their song more like speech or music? A new study contrasting pitch and spectral patterns shows that birds perceive their song more like humans perceive speech.