Digital Peer-Supported Self-Management Intervention Codesigned by People With Long COVID: Mixed Methods Proof-of-Concept Study.

BACKGROUND: There are around 1.3 million people in the United Kingdom with the devastating psychological, physical, and cognitive consequences of long COVID (LC). UK guidelines recommend that LC symptoms be managed pragmatically with holistic support for patients' biopsychosocial needs, including psychological, emotional, and physical health. Self-management strategies, such as pacing, prioritization, and goal setting, are vital for the self-management of many LC symptoms. OBJECTIVE: This paper describes the codevelopment and initial testing of a digital intervention combining peer support with positive psychology approaches for self-managing the physical, emotional, psychological, and cognitive challenges associated with LC. The objectives of this study were to (1) codesign an intervention with and for people with LC; (2) test the intervention and study methods; (3) measure changes in participant well-being, self-efficacy, fatigue, and loneliness; and (4) understand the types of self-management goals and strategies used by people with LC. METHODS: The study used a pre-post, mixed methods, pragmatic, uncontrolled design. Digital intervention content was codeveloped with a lived-experience group to meet the needs uncovered during the intervention development and logic mapping phase. The resulting 8-week digital intervention, Hope Programme for Long COVID, was attended by 47 participants, who completed pre- and postprogram measures of well-being, self-efficacy, fatigue, and loneliness. Goal-setting data were extracted from the digital platform at the end of the intervention. RESULTS: The recruitment rate (n=47, 83.9%) and follow-up rate (n=28, 59.6%) were encouraging. Positive mental well-being (mean difference 6.5, P<.001) and self-efficacy (mean difference 1.1, P=.009) improved from baseline to postcourse. All goals set by participants mapped onto the 5 goal-oriented domains in the taxonomy of everyday self-management strategies (TEDSS). The most frequent type of goals was related to activity strategies, followed by health behavior and internal strategies. CONCLUSIONS: The bespoke self-management intervention, Hope Programme for Long COVID, was well attended, and follow-up was encouraging. The sample characteristics largely mirrored those of the wider UK population with LC. Although not powered to detect statistically significant changes, the preliminary data show improvements in self-efficacy and positive mental well-being. Our next trial (ISRCTN: 11868601) will use a nonrandomized waitlist control design to further examine intervention efficacy.

Acute paediatric inpatient care of children and young people admitted with self-harm or eating disorders: A single centre evaluation.

In the United Kingdom, the prevalence of children and young people (CYP) accessing acute paediatric inpatient care with mental health problems is increasing, with self-harm and eating disorders particularly prevalent. This study evaluated CYP experiences of being in receipt of acute paediatric inpatient care following either self-harm or crisis stemming from an eating disorder to inform domains for a person-centred outcome measure (PCOM). A series of stakeholder engagement events were conducted between April and July 2015 where creative approaches were used to explore stakeholder experiences of care and to identify outcome domains that were subsequently prioritised using a Nominal Group Technique. Data were analysed using inductive thematic approach, with significance scores calculated for domain statements. Ninety-six stakeholders (15 CYP, eight parents and carers, and 73 professionals) participated. Findings showed five priority PCOM domains: privacy and surveillance; holistic care; making choices, appropriate communication; working together to achieve care goals; and respect and empowerment. This single centre evaluation highlights the need for a PCOM to be developed for this patient group that comprehensively reflects stakeholders' expectations in order to inform improvements to quality of acute paediatric care.

Cyanobacterial Abundance and Microcystin Profiles in Two Southern British Lakes: The Importance of Abiotic and Biotic Interactions.

Freshwater cyanobacteria blooms represent a risk to ecological and human health through induction of anoxia and release of potent toxins; both conditions require water management to mitigate risks. Many cyanobacteria taxa may produce microcystins, a group of toxic cyclic heptapeptides. Understanding the relationships between the abiotic drivers of microcystins and their occurrence would assist in the implementation of targeted, cost-effective solutions to maintain safe drinking and recreational waters. Cyanobacteria and microcystins were measured by flow cytometry and liquid chromatography coupled to tandem mass spectrometry in two interconnected reservoirs varying in age and management regimes, in southern Britain over a 12-month period. Microcystins were detected in both reservoirs, with significantly higher concentrations in the southern lake (maximum concentration >7 µg L-1). Elevated microcystin concentrations were not positively correlated with numbers of cyanobacterial cells, but multiple linear regression analysis suggested temperature and dissolved oxygen explained a significant amount of the variability in microcystin across both reservoirs. The presence of a managed fishery in one lake was associated with decreased microcystin levels, suggestive of top down control on cyanobacterial populations. This study supports the need to develop inclusive, multifactor holistic water management strategies to control cyanobacterial risks in freshwater bodies.

The effect of vitamin D supplementation on the risk of breast cancer: a trial sequential meta-analysis.

BACKGROUND AND OBJECTIVE: Observational studies suggest an inverse association between circulating vitamin D levels and risk of breast cancer. However, the potential benefits of vitamin D supplementation to reduce the risk of breast cancer remain controversial, based on the results of current randomized controlled trials (RCTs). The aim of this study was to evaluate the value of vitamin D supplementation on breast cancer prevention. METHODS: PubMed, Embase, and Cochrane library were searched from inception to February 2020. We performed a trial sequential meta-analysis of RCTs reporting the effect of vitamin D supplementation, with or without calcium, on the risk of breast cancer. The effect was estimated using a relative risk reduction threshold of 30%. RESULTS: Eight trials comprising 72,275 participants were included in this study, with a median follow-up period ranging from 1 to 11.9 years. The median dosage of vitamin D supplementation was 967 IU per day (range 400-3704 IU per day) across the trials. This study yielded a relative risk of 1.04 (95% CI 0.85-1.29, P = 0.68) for the effect of vitamin D supplementation (6 trials, 33,472 participants), and 0.99 (95% CI 0.91-1.07, P = 0.73) for co-administration of vitamin D and calcium (4 trials, 41,957 participants). The effect estimate for vitamin D with or without calcium on breast cancer risk lay within the futility boundary, indicating that vitamin D supplementation does not alter the relative risk by 30% or more. CONCLUSION: Our analyses suggest that vitamin D supplementation, with or without calcium, does not reduce breast cancer risk by 30% or more. Future trials with similar designs are unlikely to alter this finding.

Development and single-laboratory validation of a UHPLC-MS/MS method for quantitation of microcystins and nodularin in natural water, cyanobacteria, shellfish and algal supplement tablet powders.

A simple, rapid UHPLC-MS/MS method has been developed and optimised for the quantitation of microcystins and nodularin in wide variety of sample matrices. Microcystin analogues targeted were MC-LR, MC-RR, MC-LA, MC-LY, MC-LF, LC-LW, MC-YR, MC-WR, [Asp3] MC-LR, [Dha7] MC-LR, MC-HilR and MC-HtyR. Optimisation studies were conducted to develop a simple, quick and efficient extraction protocol without the need for complex pre-analysis concentration procedures, together with a rapid sub 5min chromatographic separation of toxins in shellfish and algal supplement tablet powders, as well as water and cyanobacterial bloom samples. Validation studies were undertaken on each matrix-analyte combination to the full method performance characteristics following international guidelines. The method was found to be specific and linear over the full calibration range. Method sensitivity in terms of limits of detection, quantitation and reporting were found to be significantly improved in comparison to LC-UV methods and applicable to the analysis of each of the four matrices. Overall, acceptable recoveries were determined for each of the matrices studied, with associated precision and within-laboratory reproducibility well within expected guidance limits. Results from the formalised ruggedness analysis of all available cyanotoxins, showed that the method was robust for all parameters investigated. The results presented here show that the optimised LC-MS/MS method for cyanotoxins is fit for the purpose of detection and quantitation of a range of microcystins and nodularin in shellfish, algal supplement tablet powder, water and cyanobacteria. The method provides a valuable early warning tool for the rapid, routine extraction and analysis of natural waters, cyanobacterial blooms, algal powders, food supplements and shellfish tissues, enabling monitoring labs to supplement traditional microscopy techniques and report toxicity results within a short timeframe of sample receipt. The new method, now accredited to ISO17025 standard, is simple, quick, applicable to multiple matrices and is highly suitable for use as a routine, high-throughout, fast turnaround regulatory monitoring tool.

Evaluating the UK House of Commons Science and Technology Committee's position on the implausible effectiveness of homeopathic treatments.

In 2009, the UK House of Commons Science and Technology Committee (STC) conducted an 'evidence check' on homeopathy to evaluate evidence for its effectiveness. In common with the wider literature critical of homeopathy, the STC report seems to endorse many of the strong claims that are made about its implausibility. In contrast with the critical literature, however, the STC report explicitly does not place any weight on implausibility in its evaluation. I use the contrasting positions of the STC and the wider critical literature to examine the 'implausibility arguments' against homeopathy and the place of such arguments within evidence-based medicine (EBM). I argue that the STC report undervalues its strong claims about the mechanistic plausibility of homeopathy because it relies on a misunderstanding about the role of mechanistic evidence within EBM. This is not a conclusion for a revision of the role mechanistic evidence plays within EBM, however. It is a conclusion about the inconsistency of the STC report's position towards implausibility arguments, given the evidential claims they endorse and the atypical situation that homeopathy presents. It provides a further example of the general point that mechanistic reasoning should not be seen as providing categorically lower quality evidence.

Comparison of the biological effects of exogenous and endogenous 1,25-dihydroxyvitamin D3 on the mature osteoblast cell line MLO-A5.

Clinical and animal data indicate that serum 25-hydroxyvitamin D3 (25D) exerts an anabolic effect on bone while serum 1α,25-dihydroxyvitamin D3 (1,25D) stimulates bone mineral loss, although the mechanism responsible for these divergent actions is unknown. Biological effects of 25D on bone cells are dependent on the local conversion to 1,25D by the 25-hydroxyvitamin D-1α-hydroxylase enzyme, CYP27B1. Therefore, identification of possible differential activities of locally produced and exogenously supplied 1,25D in bone is likely to be informative for guiding optimal administration of vitamin D supplements for bone health. The mature osteoblastic cell line MLO-A5 expresses both the vitamin D receptor (Vdr) and Cyp27b1, and therefore is a suitable model for comparing the activities of 1,25D arising from these sources. Biologically, exogenous and endogenous sources of 1,25D have similar effects on proliferation, mineralisation and induction of a range of genes by MLO-A5 osteoblasts under osteogenic conditions although endogenous 1,25D levels are markedly lower than exogenous levels. Significant differences of pharmacokinetics and pharmacodynamics of 1,25D are evident between these two sources particularly in terms of modulating gene expression for Cyp24a1 and other genes largely expressed by embedded osteoblasts/osteocytes suggesting that endogenously synthesised 1,25D is more efficiently utilised by the differentiating osteoblast.

'Midwives Overboard!' Inside their hearts are breaking, their makeup may be flaking but their smile still stays on.

PROBLEM: Midwifery practice is emotional and, at times, traumatic work. Cumulative exposure to this, in an unsupportive environment can result in the development of psychological and behavioural symptoms of distress. BACKGROUND: As there is a clear link between the wellbeing of staff and the quality of patient care, the issue of midwife wellbeing is gathering significant attention. Despite this, it can be rare to find a midwife who will publically admit to how much they are struggling. They soldier on, often in silence. AIM: This paper aims to present a narrative review of the literature in relation to work-related psychological distress in midwifery populations. Opportunities for change are presented with the intention of generating further conversations within the academic and healthcare communities. METHODS: A narrative literature review was conducted. FINDINGS: Internationally, midwives experience various types of work-related psychological distress. These include both organisational and occupational sources of stress. DISCUSSION: Dysfunctional working cultures and inadequate support are not conducive to safe patient care or the sustained progressive development of the midwifery profession. New research, revised international strategies and new evidence based interventions of support are required to support midwives in psychological distress. This will in turn maximise patient, public and staff safety. CONCLUSIONS: Ethically, midwives are entitled to a psychologically safe professional journey. This paper offers the principal conclusion that when maternity services invest in the mental health and wellbeing of midwives, they may reap the rewards of improved patient care, improved staff experience and safer maternity services.

1,25-Dihydroxyvitamin D3 and extracellular calcium promote mineral deposition via NPP1 activity in a mature osteoblast cell line MLO-A5.

While vitamin D supplementation is common, the anabolic mechanisms that improve bone status are poorly understood. Under standard mineralising conditions including media ionised calcium of 1.1 mM, 1,25-dihydroxyvitamin D3 (1,25D) enhanced differentiation and mineral deposition by the mature osteoblast/pre-osteocyte cell line, MLO-A5. This effect was markedly increased with a higher ionised calcium level (1.5 mM). Gene expression analyses revealed that 1,25D-induced mineral deposition was associated with induction of Enpp1 mRNA, coding for nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) and NPP1 protein levels. Since MLO-A5 cells express abundant alkaline phosphatase that was not further modified by 1,25D treatment or exposure to increased calcium, this finding suggested that the NPP1 production of pyrophosphate (PPi) may provide alkaline phosphatase with substrate for the generation of inorganic phosphate (Pi). Consistent with this, co-treatment with Enpp1 siRNA or a NPP1 inhibitor, PPADS, abrogated 1,25D-induced mineral deposition. These data demonstrate that 1,25D stimulates osteoblast differentiation and mineral deposition, and interacts with the extracellular calcium concentration. 1,25D regulates Enpp1 expression, which presumably, in the context of adequate tissue non-specific alkaline phosphatase activity, provides Pi to stimulate mineralisation. Our findings suggest a mechanism by which vitamin D with adequate dietary calcium can improve bone mineral status.

Selenium in sediments and biota from estuaries of southwest England.

Selenium concentrations have been measured in sediment, fucoid macroalgae and macroinvertebrates from four estuaries of SW England (Yealm, Plym, Looe, Fal). Sediment concentrations ranged from about 0.4 µg g(-1) in the Yealm to 1.49 µg g(-1) at one site in the Plym. Concentrations in Fucus vesiculosus (0.05-0.31 µg g(-1)) and F. ceranoides (0.05-0.51 µg g(-1)) were significantly lower than corresponding concentrations in sediment but there was no correlation between algal and sediment concentrations. Selenium concentrations in Littorina littorea (~4 µg g(-1)), Hediste diversicolor (2.82-12.68 µg g(-1)), Arenicola marina (~17 µg g(-1)) and Scrobicularia plana (1.18-6.85 µg g(-1)) were considerably higher than concentrations in macroalga or sediment, suggesting that Se is effectively accumulated from the diet. Although Se concentrations in some invertebrates exceed toxicity thresholds for the diet of predacious birds and fish, no specific evidence for Se toxicity exists in these estuaries.

The pleiotropic effects of vitamin D in bone.

A current controversial question related to vitamin D supplementation is what level of serum 25-hydroxyvitamin D3 (25(OH)D3) is required to reduce the incidence of osteoporotic fractures. The reasoning behind vitamin D supplementation has been mostly derived from the role of vitamin D to promote intestinal calcium absorption and reduce bone resorption. While minimum 25(OH)D3 levels of 20nmol/L are required for sufficient intestinal calcium absorption to prevent osteomalacia, the mechanistic details of how higher 25(OH)D3 levels, well beyond that required for optimal calcium absorption, are able to prevent fractures and increase bone mineral density is unclear. Substantial evidence has arisen over the past decade that conversion of 25(OH)D3 to 1,25(OH)2D3via the 1-alpha hydroxylase (CYP27B1) enzyme in osteoblasts, osteocytes, chondrocytes and osteoclasts regulates processes such as cell proliferation, maturation and mineralization as well as bone resorption, which are all dependent on the presence the of the vitamin D receptor (VDR). We and others have also shown that increased vitamin D activity in mature osteoblasts by increasing levels of VDR or CYP27B1 leads to improved bone mineral volume using two separate transgenic mouse models. While questions remain regarding activities of vitamin D in bone to influence the anabolic and catabolic processes, the biological importance of vitamin D activity within the bone is unquestioned. However, a clearer understanding of the varied mechanisms by which vitamin D directly and indirectly influences mineral bone status are required to support evidence-based recommendations for vitamin D supplementation to reduce the risk of fractures. This article is part of a Special Issue entitled 'Vitamin D workshop'.

Phosphorus loadings associated with a park tourist attraction: limnological consequences of feeding the fish.

The Linesville spillway of Pymatuning State Park is one of the most visited tourist attractions in Pennsylvania, USA, averaging more than 450,000 visitors . year(-1). Carp (Cyprinus carpio Linnaeus) and waterfowl congregate at the spillway where they are fed bread and other foods by park visitors. We hypothesized that the "breadthrowers" constitute a significant nutrient vector to the upper portion of Pymatuning Reservoir. In the summer of 2002, we estimated phosphorus loadings attributable to breadthrowers, and compared these values to background loadings from Linesville Creek, a major tributary to the upper reservoir. Items fed to fish included bread, donuts, bagels, canned corn, popcorn, corn chips, hot dogs, birthday cakes, and dog food. Phosphorus loading associated with park visitors feeding fish was estimated to be 3233 g day(-1), and estimated P export from the Linesville Creek watershed was 2235 g.day(-1). P loading attributable to breadthrowers exceeded that of the entire Linesville Creek watershed on 33 of the 35 days of study, with only a heavy rainfall event triggering watershed exports that exceeded spillway contributions. Averaged across 5 weeks, breadthrowers contributed 1.45-fold more P to Pymatuning Reservoir than the Linesville Creek watershed. If Linesville Creek P exports are extrapolated to the entire Sanctuary Lake watershed, spillway contributions of P added 48% to the non-point source watershed P entering the lake. Park visitors feeding fish at the Linesville Spillway are a significant source of nutrients entering Sanctuary Lake.