Hypothalamus Connectivity in Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling illness of unknown etiology. Increasing evidence suggests hypothalamic involvement in ME/CFS pathophysiology, which has rarely been explored using magnetic resonance imaging (MRI) in the condition. This work aimed to use MRI to examine hypothalamus connectivity in adolescents with ME/CFS and explore how this relates to fatigue severity and illness duration. 25 adolescents with ME/CFS and 23 healthy controls completed a neuroimaging protocol consisting of structural and multishell diffusion-weighted imaging sequences, in addition to the PedsQL Multidimensional Fatigue Scale to assess fatigue severity. Information about illness duration was acquired at diagnosis. Preprocessing and streamlines tractography was performed using QSIPrep combined with a custom parcellation scheme to create structural networks. The number (degree) and weight (strength) of connections between lateralized hypothalamus regions and cortical and subcortical nodes were extracted, and relationships between connectivity measures, fatigue severity, and illness duration were performed using Bayesian regression models. We observed weak-to-moderate evidence of increased degree, but not strength, of connections from the bilateral anterior-inferior (left: pd [%] = 99.18, median [95% CI] = -22.68[-40.96 to 4.45]; right: pd [%] = 99.86, median [95% CI] = -23.35[-38.47 to 8.20]), left anterior-superior (pd [%] = 99.33, median [95% CI] = -18.83[-33.45 to 4.07]) and total left hypothalamus (pd [%] = 99.44, median [95% CI] = -47.18[-83.74 to 11.03]) in the ME/CFS group compared with controls. Conversely, bilateral posterior hypothalamus degree decreased with increasing ME/CFS illness duration (left: pd [%] = 98.13, median [95% CI]: -0.47[-0.89 to 0.03]; right: pd [%] = 98.50, median [95% CI]:-0.43[-0.82 to 0.05]). Finally, a weak relationship between right intermediate hypothalamus connectivity strength and fatigue severity was identified in the ME/CFS group (pd [%] = 99.35, median [95% CI] = -0.28[-0.51 to 0.06]), which was absent in controls. These findings suggest changes in hypothalamus connectivity may occur in adolescents with ME/CFS, warranting further investigation.

Hypoxia-sonic hedgehog axis as a driver of primitive hematopoiesis development and evolution in cavefish.

The teleost Astyanax mexicanus consists of surface dwelling (surface fish) and cave dwelling (cavefish) forms. Cavefish have evolved in subterranean habitats characterized by reduced oxygen levels (hypoxia) and exhibit a subset of phenotypic traits controlled by increased Sonic hedgehog (Shh) signaling along the embryonic midline. The enhancement of primitive hematopoietic domains, which are formed bilaterally in the anterior and posterior lateral plate mesoderm, are responsible for the development of more larval erythrocytes in cavefish relative to surface fish. In this study, we determine the role of hypoxia and Shh signaling in the development and evolution of primitive hematopoiesis in cavefish. We show that hypoxia treatment during embryogenesis increases primitive hematopoiesis and erythrocyte development in surface fish. We also demonstrate that upregulation of Shh midline signaling by the Smoothened agonist SAG increases primitive hematopoiesis and erythrocyte development in surface fish, whereas Shh downregulation via treatment with the Smoothened inhibitor cyclopamine decreases these traits in cavefish. Together these results suggest that hematopoietic enhancement is regulated by hypoxia and Shh signaling. Lastly, we demonstrate that hypoxia enhances expression of Shh signaling along the midline of surface fish embryos. We conclude that hypoxia-mediated Shh plasticity may be a driving force for the adaptive evolution of primitive hematopoiesis and erythrocyte development in cavefish.

Hypoxia-Sonic Hedgehog Axis as a Driver of Primitive Hematopoiesis Development and Evolution in Cavefish.

The teleost Astyanax mexicanus consists of surface dwelling (surface fish) and cave dwelling (cavefish) forms. Cavefish have evolved in subterranean habitats characterized by reduced oxygen levels (hypoxia) and show constructive and regressive phenotypic traits controlled by increased Sonic hedgehog (Shh) signaling along the embryonic midline. The enhancement of primitive hematopoietic domains, which are formed bilaterally in the anterior and posterior lateral plate mesoderm, are responsible for the development of more larval erythrocytes in cavefish relative to surface fish. In this study, we determine the role of hypoxia and Shh signaling in the development and evolution of primitive hematopoiesis in cavefish. We show that hypoxia treatment during embryogenesis increases primitive hematopoiesis and erythrocyte development in surface fish. We also demonstrate that upregulation of Shh midline signaling by treatment with the Smoothened agonist SAG increases primitive hematopoiesis and erythrocyte development in surface fish, whereas Shh downregulation via treatment with the Smoothened inhibitor cyclopamine decreases these traits in cavefish. Together these results suggest that hematopoietic enhancement is regulated by hypoxia and the Shh signaling system. Lastly, we demonstrate that hypoxia treatment enhances expression of Shh signaling along the midline of surface fish embryos. Thus, we conclude that a hypoxia-Shh axis may drive the adaptive evolution of primitive hematopoiesis and erythrocyte development in cavefish. Highlights: Hypoxia increases hematopoiesis and erythrocytes in surface fishShh upregulation increases hematopoiesis and erythrocytes in surface fishShh inhibition decreases hematopoiesis and erythrocytes in cavefishHypoxia upregulates Shh along the embryonic midline in surface fish.

Biodiversity patterns of the coral reef cryptobiota around the Arabian Peninsula.

The Arabian Peninsula accounts for approximately 6% of the world's coral reefs. Some thrive in extreme environments of temperature and salinity. Using 51 Autonomous Reef Monitoring Structure (ARMS), a standardized non-destructive monitoring device, we investigated the spatial patterns of coral reef cryptobenthic diversity in four ecoregions around the Arabian Peninsula and analyzed how geographical and/or environmental drivers shape those patterns. The mitochondrial cytochrome c oxidase subunit I (COI) gene was used to identify Amplicon Sequence Variants and assign taxonomy of the cryptobenthic organisms collected from the sessile and mobile fractions of each ARMS. Cryptobenthic communities sampled from the two ecoregions in the Red Sea showed to be more diverse than those inhabiting the Arabian (Persian) Gulf and the Gulf of Oman. Geographic distance revealed a stronger relationship with beta diversity in the Mantel partial correlation than environmental distance. However, the two mobile fractions (106-500 µm and 500-2000 µm) also had a significant correlation between environmental distance and beta diversity. In our study, dispersal limitations explained the beta diversity patterns in the selected reefs, supporting the neutral theory of ecology. Still, increasing differences in environmental variables (environmental filtering) also had an effect on the distribution patterns of assemblages inhabiting reefs within short geographic distances. The influence of geographical distance in the cryptofauna assemblages makes these relevant, yet usually ignored, communities in reef functioning vulnerable to large scale coastal development and should be considered in ecosystem management of such projects.

Customised knowledge-sharing platform to foster resident quality improvement activities, tracking and scholarship.

INTRODUCTION: Meeting accreditation requirements to train resident physicians in quality improvement (QI) may require more than education. Barriers to resident QI engagement underscore the need to demonstrate the impact and value of resident QI work. It is not known whether a platform to track and publicise resident QI projects and scholarship is feasible or acceptable to implement within a residency programme. We aimed to create a searchable online platform and associated programming to promote resident QI work. METHODS: This intervention targeted resident physicians in an internal medicine residency training programme at a tertiary, academic medical centre. We designed an intervention to track resident QI and related scholarship in a searchable online platform, including practical details of implementing each project. Newsletters and events were used to publicise these project profiles. RESULTS: During the 2020-2021 academic year, 104 projects were profiled from 238 sourced projects. Average readership was 31.5% across 11 newsletters sent to residents and key faculty. DISCUSSION: A platform to track and share resident QI work and scholarship can be feasibly and acceptably implemented within a residency programme, serving as a novel way to engage residents around QI.

The impact of intranasal corticosteroids in a prospective cohort of children with sleep disordered breathing.

INTRODUCTION: Sleep disordered breathing (SDB) is common in children and the most common reason for adenotonsillectomy. This large observational cohort study from a specialist outpatient clinic describes the impact of intranasal steroids (INS) on symptom improvement and the need for surgery. METHOD: Observational cohort study of 568 children assessing the impact of INS using the OSA-5 questionnaire with clinical and surgical outcome measures. RESULTS: The mean OSA-5 score at first visit was 7.78. Symptoms were persistent for a median 9 months (range 2-72). 51% underwent a trial of INS with 56% reporting symptomatic improvement. The mean score decreased from 8.2 to 5.5 (p < 0.0001) in those prescribed INS. They had a significantly higher symptom load (p < 0.01), turbinate size (p < 0.005) and history of atopy (p < 0.01) than the non-trial group. The rate of surgery in the non-trial group was 56% compared with 38% in those who had INS (p < 0.001). With increasing symptom burden, the reported improvement with INS and comparative reduction in surgery increased. Baseline OSA-5 scores were predictive of rates of surgery. Atopic status or age did not influence response to INS. CONCLUSION: The mean score at first visit and the median duration of symptoms indicated significant persistent symptoms in this cohort. The use of INS improved symptoms of SDB in 56%. The need for surgery in the group that received INS was 38% compared with 56% in those not trialling INS, despite the non-trial group having significantly less symptoms and signs. Symptomatic improvement was not influenced by age or atopic status.

Preparing Preclinical Medical Students for Routine Code Status Discussions: A Mixed-Methods Study.

CONTEXT: Medical students are expected to gain competency in inquiring about patients' goals of care, per the Association of American Medical Colleges' Entrustable Professional Activities. While students may be part of teams that conduct routine code status discussions (CSDs), formal training in this skill prior to clinical clerkships is lacking. OBJECTIVES: We aimed to address this training gap by designing a curriculum to teach preclinical medical students about routine CSDs. METHODS: We designed and conducted an interactive workshop for preclinical medical students to learn about routine CSDs and practice this skill, using Kern's Six Steps to Curriculum Design. A qualitative and quantitative pre- and postsurvey was administered. A convergent, parallel, mixed methods analysis was performed. RESULTS: Students (n = 135) named more options for code status following the workshop (presurvey 1.3 vs. postsurvey 4.3, P < 0.01). There was an increase in the proportion of students reporting that they felt "somewhat comfortable" or "extremely comfortable" conducting a CSD (presurvey 19% vs. postsurvey 64%, P < 0.01), and a decrease in those reporting that they felt "extremely uncomfortable" or "somewhat uncomfortable" (presurvey 53% vs. postsurvey 18%, P < 0.01). Thematic analysis revealed that students were concerned about knowledge gaps, communication tools, personal discomfort, and upsetting patients or family. CONCLUSION: A workshop to train medical students to conduct routine CSDs can be included as part of a preclinical medical education curriculum. Students reported that the workshop increased their confidence in conducting CSDs and demonstrated an increase in corresponding knowledge, preparing them to deliver person-centered care on their clerkships.

Behavioral Interventions on Surgeons' Preoperative Decision-Making: A Scoping Review and Critical Analysis.

INTRODUCTION: Consensus is lacking regarding the optimal strategy to influence surgeons' behaviors to reduce low-value surgical care. Comprehensively describing the existing body of literature that seeks to intervene on surgeons' preoperative decision-making may aid in structuring future behavior change strategies. METHODS: We performed a scoping review using four databases (Medical Literature Analysis and Retrieval System Online, Embase, Web of Science, and Cumulated Index to Nursing and Allied Health Literature) for articles that tested the effect of behavioral-based interventions on any aspect of surgeons' decision-making in the preoperative setting. Abstracted data were characterized by summative descriptions and analyzed using the Tailored Implementation for Chronic Disease framework, mapping aspects of deimplementation strategies in the studies onto the determinant(s) that they altered. Data abstraction and mapping tools were piloted and iteratively revised before two researchers independently assessing studies and categorizing determinants, and then meeting to discuss their decisions. RESULTS: There were 1460 articles identified from the initial search, with 17 full text articles ultimately included in the scoping review. Eight studies relied on a multidisciplinary preoperative conference to accomplish their aims, while five were multifaceted in their approach to deimplementation, and four studies used only a clinical decision support tool to accomplish their aims. Mapping determinants addressed in these studies onto the Tailored Implementation for Chronic Disease framework demonstrated that most strategies attempted to close knowledge gaps, leverage communication between providers, and broadcast institutional prioritization of change. CONCLUSIONS: There is a small but growing field of implementation and deimplementation strategies in preoperative surgical decision-making, and different approaches may be equally effective in varied clinical contexts. Deliberate measurement and comparison of outcomes, as well as selection of control groups, are areas for improvement in future work.

Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): impact of self-reported fatigue and illness duration.

Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex illness of unknown aetiology. Emerging theories suggest ME/CFS may reflect a progressive, aberrant state of homeostasis caused by disturbances within the hypothalamus, yet few studies have investigated this using magnetic resonance imaging in adolescents with ME/CFS. We conducted a volumetric analysis to investigate whether whole and regional hypothalamus volumes in adolescents with ME/CFS differed compared to healthy controls, and whether these volumes were associated with fatigue severity and illness duration. 48 adolescents (25 ME/CFS, 23 controls) were recruited. Lateralised whole and regional hypothalamus volumes, including the anterior-superior, superior tubular, posterior, anterior-inferior and inferior tubular subregions, were calculated from T1-weighted images. When controlling for age, sex and intracranial volume, Bayesian linear regression models revealed no evidence for differences in hypothalamus volumes between groups. However, in the ME/CFS group, a weak linear relationship between increased right anterior-superior volumes and fatigue severity was identified, which was absent in controls. In addition, Bayesian quantile regression revealed a likely-positive association between illness duration and right superior tubular volumes in the ME/CFS group. While these findings suggest overall comparability in regional and whole hypothalamus volumes between adolescents with ME/CFS and controls, preliminary evidence was identified to suggest greater fatigue severity and longer illness duration were associated with greater right anterior-superior and superior-tubular volumes, respectively. These regions contain the anterior and superior divisions of the paraventricular nucleus, involved in the neuroendocrine response to stress, suggesting involvement in ME/CFS pathophysiology. However, replication in a larger, longitudinal cohort is required.

What lies beneath: White matter microstructure in pediatric myalgic encephalomyelitis/chronic fatigue syndrome using diffusion MRI.

Recent studies in adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that changes in brain white matter microstructural organization may correlate with core ME/CFS symptoms, and represent a potential biomarker of disease. However, this has yet to be investigated in the pediatric ME/CFS population. We examined group differences in macrostructural and microstructural white matter properties, and their relationship with clinical measures, between adolescents recently diagnosed with ME/CFS and healthy controls. Forty-eight adolescents (25 ME/CFS, 23 controls, mean age 16 years) underwent brain diffusion MRI, and a robust multi-analytic approach was used to evaluate white and gray matter volume, regional brain volume, cortical thickness, fractional anisotropy, mean/axial/radial diffusivity, neurite dispersion and density, fiber density, and fiber cross section. From a clinical perspective, adolescents with ME/CFS showed greater fatigue and pain, poorer sleep quality, and poorer performance on cognitive measures of processing speed and sustained attention compared with controls. However, no significant group differences in white matter properties were observed, with the exception of greater white matter fiber cross section of the left inferior longitudinal fasciculus in the ME/CFS group compared with controls, which did not survive correction for intracranial volume. Overall, our findings suggest that white matter abnormalities may not be predominant in pediatric ME/CFS in the early stages following diagnosis. The discrepancy between our null findings and white matter abnormalities identified in the adult ME/CFS literature could suggest that older age and/or longer illness duration influence changes in brain structure and brain-behavior relationships that are not yet established in adolescence.

Effectiveness of Intranasal Mometasone Furoate vs Saline for Sleep-Disordered Breathing in Children: A Randomized Clinical Trial.

Importance: Obstructive sleep-disordered breathing (SDB) in children is characterized by snoring and difficulty breathing during sleep. SDB affects at least 12% of otherwise healthy children and is associated with significant morbidity. Evidence from small clinical trials suggests that intranasal corticosteroids improve SDB as measured by polysomnography; however, the effect on symptoms and quality of life is unclear. Objective: To determine whether intranasal mometasone furoate is more effective than intranasal saline for improving symptoms and quality of life in children with SDB. Design, Setting, and Participants: The MIST trial was a multicenter, randomized, double-blind, placebo-controlled trial, recruiting participants from June 8, 2018, to February 13, 2020. Children aged 3 to 12 years who were referred to a specialist for significant SDB symptoms were included; exclusions were previous adenotonsillectomy, body mass index greater than the 97th percentile, and severe SDB. Randomization was stratified by site, and data were analyzed on an intention-to-treat basis from October 28, 2020, to September 25, 2022. Interventions: Participants were randomly assigned to receive mometasone furoate, 50 µg, or sodium chloride (saline), 0.9%, 1 spray per nostril daily, dispensed in identical bottles. Main Outcomes and Measures: The primary outcome was resolution of significant SDB symptoms (ie, reduction to a level no longer requiring referral to a specialist as per the American Academy of Pediatrics guidelines) at 6 weeks, measured by parental report of symptoms using the SDB Score. Results: A total of 276 participants (mean [SD] age, 6.1 [2.3] years; 146 male individuals [53%]) were recruited, 138 in each treatment arm. Resolution of significant SDB symptoms occurred in 56 of 127 participants (44%) in the mometasone group and 50 of 123 participants (41%) in the saline group (risk difference, 4%; 95% CI, -8% to 16%; P = .51) with 26 participants lost to follow-up and missing values managed by multiple imputation. The main adverse effects were epistaxis, affecting 12 of 124 participants (9.7%) in the mometasone group and 18 of 120 participants (15%) in the saline group, and nasal itch/irritation, affecting 12 of 124 participants (9.7%) in the mometasone group and 22 of 120 participants (18%) in the saline group. Conclusions and Relevance: Results of this randomized clinical trial suggest that there was no difference in treatment effect between intranasal mometasone and saline for the management of SDB symptoms. The results suggest that almost one-half of children with SDB could be initially managed in the primary care setting and may not require referral to specialist services, as is currently recommended. Trial Registration: Australian New Zealand Clinical Trials Registry: ANZCTRN12618000448246.

Evaluation of interdisciplinary care pathway implementation in older elective surgery patients.

BACKGROUND: The American College of Surgeons Geriatric Surgery Verification Program outlines best practices for surgical care in older adults. These recommendations have guided institutions to create workflows to better support needs specific to older surgical patients. This qualitative study explored clinician experiences to understand influences on implementation of frailty screening and an interdisciplinary care pathway in older elective colorectal surgery and neurosurgery patients. STUDY DESIGN: Semi-structured in-person and video-based interviews were conducted from July 2021 to March 2022 with clinicians caring for patients ≥70 years on the colorectal surgery and neurosurgery services. Interviews addressed familiarity with and beliefs about the intervention, intervention alignment with routine workflow and workflow adaptations, and barriers and facilitators to performing the intervention. Interviews were analyzed using the consolidated framework for implementation research (CFIR) to find themes related to ongoing implementation. RESULTS: Thirty-two clinicians participated (56.3% female, 58.8% White). Fifteen relevant CFIR constructs were identified. Key themes to implementation success included strong participant belief in effectiveness of the intervention and its advantage over standard care; the importance of training, reference materials, and champions; and the need for institution-level investment in resources to amplify the impact of the intervention on patients and expand the capacity to address their needs. CONCLUSION: Systematic evaluation found implementation of frailty screening and an interdisciplinary care pathway in elective colorectal surgery and neurosurgery patients to be supported by participating clinicians, yet sustainability of the intervention and further adoption across surgical services to better meet the needs of older patients would necessitate organizational resource allocation.

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Adolescents: Practical Guidance and Management Challenges.

This paper reviews the current understanding of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and whether any treatment strategies have been effective. ME/CFS is a condition of as yet unknown etiology that commonly follows an infective process. It includes a new onset of fatigue (of more than 3-6 month duration and not relieved by rest), post-exertional malaise, cognitive difficulties and unrefreshing sleep, and frequently orthostatic intolerance, somatic symptoms and pain. Long COVID has renewed interest in the condition and stimulated research with findings suggestive of a multisystem neuroimmune disease. There are no definitively effective treatments. Despite earlier recommendations regarding graded exercise therapy and cognitive behavior therapy, the current recommendations are managing symptoms, with lifestyle management and supportive care. This paper provides an outline of strategies that young people and their families have reported as helpful in managing a chronic illness that impacts their life socially, physically, emotionally, cognitively and educationally. As the illness frequently occurs at a time of rapid developmental changes, reducing these impacts is reported to be as important as managing the physical symptoms. Young people face a mean duration of 5 years illness (range 1-16 years) with a likely residual 20% having significant restrictions after 10 years. Their feedback has suggested that symptom management, self-management strategies, advocacy and educational liaison have been the most helpful. They value professionals who will listen and take them seriously, and after excluding alternative diagnoses, they explain the diagnosis, are supportive and assist in monitoring their progress. Remaining engaged in education was the best predictor of later functioning. This allowed for social connections, as well as potential independence and fulfilling some aspirations. The need to consider the impact of this chronic illness on all aspects of adolescent development, as part of management, is highlighted.

Comparative Outcomes and Surgical Timing for Operative Fragility Hip Fracture Patients during the COVID-19 Pandemic: A Retrospective Cohort Study.

The COVID-19 pandemic had wide-reaching effects on healthcare delivery, including care for hip fractures, a common injury among older adults. This study characterized factors related to surgical timing and outcomes, length-of-stay, and discharge disposition among patients treated for operative hip fractures during the first wave of the COVID-19 pandemic, compared to historical controls. A retrospective, observational cohort study was conducted from 16 March-20 May 2020 with a consecutive series of 64 operative fragility hip fracture patients at three tertiary academic medical centers. Historical controls were matched based on sex, surgical procedure, age, and comorbidities. Primary outcomes included 30-day mortality and time-to-surgery. Secondary outcomes included 30-day postoperative complications, length-of-stay, discharge disposition, and time to obtain a COVID-19 test result. There was no difference in 30-day mortality, complication rates, length-of-stay, anesthesia type, or time-to-surgery, despite a mean time to obtain a final preoperative COVID-19 test result of 17.6 h in the study group. Notably, 23.8% of patients were discharged to home during the COVID-19 pandemic, compared to 4.8% among controls (p = 0.003). On average, patients received surgical care within 48 h of arrival during the COVID-19 pandemic. More patients were discharged to home rather than a facility with no change in complications, suggesting an opportunity for increased discharge to home.

Contrasting heat stress response patterns of coral holobionts across the Red Sea suggest distinct mechanisms of thermal tolerance.

Corals from the northern Red Sea, in particular the Gulf of Aqaba (GoA), have exceptionally high bleaching thresholds approaching >5℃ above their maximum monthly mean (MMM) temperatures. These elevated thresholds are thought to be due to historical selection, as corals passed through the warmer Southern Red Sea during recolonization from the Arabian Sea. To test this hypothesis, we determined thermal tolerance thresholds of GoA versus central Red Sea (CRS) Stylophora pistillata corals using multi-temperature acute thermal stress assays to determine thermal thresholds. Relative thermal thresholds of GoA and CRS corals were indeed similar and exceptionally high (~7℃ above MMM). However, absolute thermal thresholds of CRS corals were on average 3℃ above those of GoA corals. To explore the molecular underpinnings, we determined gene expression and microbiome response of the coral holobiont. Transcriptomic responses differed markedly, with a strong response to the thermal stress in GoA corals and their symbiotic algae versus a remarkably muted response in CRS colonies. Concomitant to this, coral and algal genes showed temperature-induced expression in GoA corals, while exhibiting fixed high expression (front-loading) in CRS corals. Bacterial community composition of GoA corals changed dramatically under heat stress, whereas CRS corals displayed stable assemblages. We interpret the response of GoA corals as that of a resilient population approaching a tipping point in contrast to a pattern of consistently elevated thermal resistance in CRS corals that cannot further attune. Such response differences suggest distinct thermal tolerance mechanisms that may affect the response of coral populations to ocean warming.

Health, Wellbeing, and Prognosis of Australian Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case-Controlled Follow-Up Study.

BACKGROUND: The purpose of this study was to follow-up an Australian cohort of adolescents newly-diagnosed with ME/CFS at a tertiary paediatric ME/CFS clinic and healthy controls over a mean period of two years (range 1-5 years) from diagnosis. Objectives were to (a) examine changes over time in health and psychological wellbeing, (b) track ME/CFS symptomatology and fulfillment of paediatric ME/CFS diagnostic criteria over time, and (c) determine baseline predictors of ME/CFS criteria fulfilment at follow-up. METHODS: 34 participants aged 13-18 years (25 ME/CFS, 23 controls) completed standardised questionnaires at diagnosis (baseline) and follow-up assessing fatigue, sleep quality and hygiene, pain, anxiety, depression, and health-related quality of life. ME/CFS symptomatology and diagnostic criteria fulfilment was also recorded. RESULTS: ME/CFS patients showed significant improvement in most health and psychological wellbeing domains over time, compared with controls who remained relatively stable. However, fatigue, pain, and health-related quality of life remained significantly poorer amongst ME/CFS patients compared with controls at follow-up. Sixty-five percent of ME/CFS patients at baseline continued to fulfil ME/CFS diagnostic criteria at follow-up, with pain the most frequently experienced symptom. Eighty-two percent of patients at follow-up self-reported that they still had ME/CFS, with 79% of these patients fulfilling criteria. No significant baseline predictors of ME/CFS criteria fulfilment at follow-up were observed, although pain experienced at baseline was significantly associated with criteria fulfilment at follow-up (R = 0.6, p = 0.02). CONCLUSIONS: The majority of Australian adolescents with ME/CFS continue to fulfil diagnostic criteria at follow-up, with fatigue, pain, and health-related quality of life representing domains particularly relevant to perpetuation of ME/CFS symptoms in the early years following diagnosis. This has direct clinical impact for treating clinicians in providing a more realistic prognosis and highlighting the need for intervention with young people with ME/CFS at the initial diagnosis and start of treatment.

Paediatric patients with myalgic encephalomyelitis/chronic fatigue syndrome value understanding and help to move on with their lives.

AIM: The aim of this study was to document qualitative questionnaire feedback regarding management from a cohort observational study of young people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). METHODS: Between 1991 and 2009, 784 paediatric patients, age 6-18 years, were diagnosed with ME/CFS following referral to a specialised clinic at the Royal Children's Hospital, Melbourne. Over a 14-year period, feedback was requested on up to seven occasions. Management included the following: symptom management and a self-management lifestyle plan that included social, educational, physical and a pleasurable activity outside of home. They adjusted it by severity of illness, stage of education, family circumstances and life interests. RESULTS: Questionnaires were returned from 626 (80%) with 44% providing feedback more than once. They reported that their management plan allowed them to regain control over their lives. They cited early diagnosis, empathetic, informed physicians, self-management strategies and educational liaison as helping them to function and remain socially engaged. Ongoing support, particularly assistance to navigate the education system, was essential for general well-being and ability to cope. CONCLUSION: Young people valued regaining the control over their lives that was lost through illness, support to maintain social contacts and assistance to achieve educational and/or life goals.

Our experience of a paediatrician-led clinic for the medical management of children with obstructive sleep-disordered breathing.

BACKGROUND: Obstructive sleep-disordered breathing (OSDB) is very common in children. Adenotonsillectomy is usually curative, but there is emerging evidence that topical nasal steroids can also be effective for some children and may avoid the need for surgery. The number of children referred for assessment of OSDB is increasing and in some departments, waiting times are long. We established a paediatrician-led clinic for assessment and initial medical management of OSDB and in this study we report the proportion of children who avoided the need for surgery. METHOD: Referral letters to the otolaryngology department were screened and those with suspected OSDB and no significant co-morbidities were diverted to the paediatrician-led clinic. We recorded data for a consecutive series of children seen in this clinic with suspected OSDB over a 3-month period. Parents completed a 5-item subset of questions from the OSA-11 questionnaire before and after treatment with 6 weeks of topical nasal steroids. RESULTS: In the 3-month study period, 103 children were seen, with a mean age of 6 (range 1-16). Six (5.8%) had improved spontaneously before clinic attendance. Of the 97 children who were still symptomatic, 17 (17.5%) were referred directly for surgery on the basis of the severity of their symptoms, or because of other coexisting conditions that required surgical treatment (such as recurrent tonsillitis or otitis media). Three declined intranasal steroids. Seventy-seven had a trial of intranasal steroids, of whom 34 (35%) reported enough improvement to avoid surgery, and 29 (28%) failed to improve and were referred for surgery. Fourteen (14%) failed to attend after the trial of steroids: of these, 5 (5%) were contactable by phone and confirmed improvement after topical steroids. OSA-5 scores were significantly improved following intranasal steroids. DISCUSSION: A paediatrician-led clinic can be an effective way to ease the workload of an over-stretched otolaryngology service, and judicious use of topical nasal steroids can help around 40% of children with OSDB avoid surgery.

Silicic acid limitation drives bloom termination and potential carbon sequestration in an Arctic bloom.

The spring diatom bloom in the Arctic Ocean accounts for significant annual primary production leading to the most rapid annual drawdown of water-column pCO2. Late-winter waters in the Atlantic Arctic & Subarctic Provinces (AASP) have lower silicic acid concentrations than nitrate, which suggests diatom blooms may deplete Si before N. Here we test a facet of the hypothesis that silicic acid limitation terminates the spring diatom bloom in the AASP and the sinking of the senescent and dead diatoms helps drive carbon sequestration. During a 6-week study, diatoms bloomed and progressively consumed silicic acid to where it limited their growth. The onset of growth limitation was concurrent with the minimum pCO2 in the surface waters and increases in both the proportion of dead diatoms and the diatom assemblage sedimentation rate. Data reanalysis within the AASP shows a highly significant and positive correlation between silicic acid and pCO2 in the surface waters, but no significant relationship with nitrate and pCO2 was observed unless data were smoothed. Therefore, understanding the future of the AASP spring diatom bloom requires models that explicitly consider changes in silicic acid supply as a driver of this process.

Long Term Follow up of Young People With Chronic Fatigue Syndrome Attending a Pediatric Outpatient Service.

Aim: To determine the reported duration of illness, the functional and educational long-term outcomes, predictive factors for recovery and seek feedback regarding management in pediatric/adolescent myalgic encepahalomyelitis/chronic fatigue syndrome (ME/CFS). Methods: A cohort observational study of 784 young people, mean age 14.6 (6-18) years, with ME/CFS diagnosed at a specialist pediatric hospital and receiving regular care, was conducted with follow-up for a mean 8 (range 1-21) years after onset. Baseline symptoms, history, depression and anxiety questionnaires were available from 418. The remaining 366, did not have similar standardized baseline information. Questionnaires requested functional rating, persistent symptoms, duration of illness if "recovered," social engagement and school/work attendance. Feedback was sought regarding management, support services, useful information, helpful interventions or personnel and use of alternative therapies. Reported recovery and function were compared with baseline information and between the two groups. Results: Follow-up data were returned from 81.8%. There was no significant difference in functional score (if reported recovery) or illness duration related to provision of baseline data. The mean duration of illness was 5 (range 1-15) years in the 50% who reported recovery. By 5 years 38% and by 10 years 68% reported recovery. At 10 years the mean functional score was 8/10 (range 2-10) with 5% scoring <6. Depression, anxiety or severity of illness at diagnosis was not predictive of non-recovery. Designing and monitoring their own management plan that included educational, social, physical and enjoyable activities, as well as having symptom management and understanding professionals were highly valued. However, remaining engaged in an education system that flexibly accommodated their illness and aspirations was consistently reported as crucial for long term functioning. Conclusions: ME/CFS in young people has a mean duration of 5 years (1-15) with 68% reporting recovery by 10 years. All improved functionally with 5% remaining very unwell and a further 20% significantly unwell. There were no obvious baseline predictors for recovery. However, depression, anxiety, orthostatic intolerance and to a lesser extent pain at follow up were identified as hampering recovery or function. Supportive professionals, remaining engaged in education and management strategies were identified as helpful.