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Peer reviewed: True, Objectives: To assess the risk of new-onset or worsening hyperglycaemia, hypertension, weight gain and hyperlipidaemia with systemic corticosteroid therapy (CST) as reported in published randomised control trial (RCT) studies. Data sources: Literature search using MEDLINE, EMBASE, Cochrane library, Web of Science and Scopus Study eligibility criteria: Published articles on results of RCT with a systemic CST arm with numerical data presented on adverse effect (AE). Participants and interventions: Reports of hyperglycaemia, hypertension, weight gain and hyperlipidaemia associated with systemic CST in patients or healthy volunteer’s ≥17 years of age. Study appraisal methods: Risk of bias tool, assessment at the level of AE and key study characteristics. Results: A total of 5446 articles were screened to include 118 studies with 152 systemic CST arms (total participants=17 113 among which 8569 participants treated with CST). Pooled prevalence of hyperglycaemia in the CST arms within the studies was 10% (95% CI 7% to 14%), with the highest prevalence in respiratory illnesses at 22% (95% CI 9% to 35%). Pooled prevalence of severe hyperglycaemia, hypertension, weight gain and hyperlipidaemia within the corticosteroid arms was 5% (95% CI 2% to 9%), 6% (95% CI 4% to 8%), 13% (95% CI 8% to 18%), 8% (95% CI 4% to 17%), respectively. CST was significantly associated hyperglycaemia, hypertension and weight gain as noted in double-blinded placebo-controlled parallel-arms studies: OR of 2.13 (95% CI 1.66 to 2.72), 1.68 (95% CI 0.96 to 2.95) and 5.20 (95% CI 2.10 to 12.90), respectively. Intravenous therapy posed higher risk than oral therapy: OR of 2.39 (95% CI 1.16 to 4.91). Limitations: There was significant heterogeneity in the AE definitions and quality of AE reporting in the primary studies and patient populations in the studies. The impact of cumulative dose effect on incidental AE could not be calculated. Conclusions and implications of key findings: Systemic CST use is associated with increased risk of metabolic AEs, which differs for each disease group and route of administration. PROSPERO registration number: CRD42020161270.

BACKGROUND: Ambient air pollution is a pervasive and ubiquitous hazard, which has been linked to premature morbidity and a growing number of morbidity endpoints. Air pollution may be linked to neurodegeneration, and via this or other pathways, to neurodegenerative diseases. Emerging evidence suggests that air pollution may contribute to neurodegenerative diseases such as dementia, Parkinson's Disease (PD), Multiple Sclerosis (MS) and Motor Neuron Diseases (MND), although this evidence remains inconsistent and very limited for MS and MND. In addition, this evidence base is rapidly emerging and would benefit from a wide and critical synthesis, including a better understanding of heterogeneity.OBJECTIVES: In this paper, we present a protocol for a systematic review and meta-analysis and specify our methods a priori. The main aim of the planned systematic review is to answer the question of whether long-term exposure (>1 year) to ambient (outdoor) air pollution (exposure, compared to lower exposure) increases the risk of adult (population) incidence of neurodegenerative diseases (outcomes) in epidemiological observational studies (study design). Another aim is to meta-analyze the associations between long-term exposure to ambient air pollutants and the risk of the selected outcomes and assess the shape of exposure-response functions. To set the stage for the proposed work, we also overview the existing epidemiological evidence in this protocol, but do not critically evaluate it, as these results will be fully presented in the planned systematic review.SEARCH AND STUDY ELIGIBILITY: We will search the electronic databases Medline (via Ovid), Embase (via Ovid), Cochrane Library, Cinahl (via Ebscohost), Global Health (via Ebscohost), PsycINFO (via Ebscohost), Scopus, Web of Science (Core Collection), from inception to October 2022. Eligible studies must contain primary research investigating the link between 1-year + exposure to any outdoor air pollutant, from any source, and dementia, PD, MS, and MND, or dementia subtypes: Alzheimer's Disease, vascular dementia, and mixed dementia. The search strategy and eligibility criteria are pre-determined and described in full in this protocol.STUDY APPRAISAL AND SYNTHESIS METHODS: Articles will be stored and screened using Rayyan QCRI. Title and abstract screening, full text review, data extraction, risk of bias assessment and data preparation for statistical analysis will be conducted independently by two reviewers using pre-defined forms and criteria, described in this protocol. All these steps will also be piloted and the forms and/or methods adapted if issues arise. Meta-analysis and assessment of the shape of the exposure-response functions will be conducted if four independent exposure-outcomes pairs are available, and the remainder of results will be synthesized in the forms of tables and via a narrative summary. Certainty in the body of evidence will be assessed using the OHAT approach. This protocol describes the planned analysis and synthesis a priori and serves to increase transparency and impact of this systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aims to estimate the prevalence and prognostic impact of retropharyngeal lymph node metastases (RLNMs) in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: This meta-analysis was conducted according to PRISMA guidelines. INCLUSION CRITERIA: studies with more than 20 patients reporting the prevalence or prognostic impact of RLNMs in OPSCC. Whenever available, data on HPV status and subsites were extracted. RESULTS: Twenty-two articles were included. The overall prevalence of RLNMs in OPSCC was 13%, with no significant differences depending on HPV status. The highest prevalence was observed for posterior pharyngeal wall SCC (24%), followed by soft palate (17%), palatine tonsil (15%), and base of tongue (8%). RLNMs were associated with a significantly higher risk of death (HR:2.54;IC95%1.89-3.41) and progression (HR:2.44;IC95%1.80-3.30). CONCLUSIONS: The prevalence of RLNMs in OPSCC was 13%, being higher in tumors of the posterior pharyngeal wall. RLNMs were associated with unfavorable outcomes.

Objectives: Vestibular schwannomas (VS) are rare benign tumours of the vestibular nerve that cause hearing loss. Management strategies include watchful waiting, radiotherapy or surgical resection. ...

BACKGROUND: Speech development requires intact and adequately functioning oral anatomy and cognitive 'speech processing' skills. There is evidence that speech input processing skills are associated with speech output problems in children not born with a cleft. Children born with cleft palate ± lip (CP±L) are at high risk of developing disordered speech output. Less is known about their speech input processing skills and whether they are associated with cleft-related speech sound disorder (SSD). AIMS: (1) To collate and evaluate studies reporting evidence regarding the speech input processing skills of children born with cleft palate in comparison with data from typically developing children or other comparison groups; and (2) to identify any available evidence regarding relationships between speech input processing skills and speech output in children born with CP±L. METHODS & PROCEDURES: Potentially relevant studies published up to November 2019 were identified from the following databases: Medline via Ovid, Embase via Ovid, Cinahl via Ebscohost, PsycInfo via Ebscohost, BNI via ProQuest, AMED via Ovid, Cochrane Library and Scopus. Inclusion criteria were: peer-reviewed articles published in scientific journals, any design, published in English, participants born with a CP±L aged up to age 18 years who completed speech input processing assessments compared with normative data and/or a control or other comparison group. Critical Appraisal Skills Programme (CASP) checklists were used to quality appraise included studies. OUTCOMES & RESULTS: Six studies were retained in the final review. There is some evidence that children born with CP±L perform less well than non-cleft controls on some speech input processing tasks and that specific input processing skills may be related to errors in the children's speech. Heterogeneity in relation to study groups and assessments used, as well as small sample sizes, limits generalization of findings. CONCLUSION & IMPLICATIONS: There is limited evidence regarding the speech input processing skills of children born with CP±L. There are indications that children born with CP+/L may have difficulty in some aspects of speech input processing in comparison with children not born with a cleft, and that difficulties with some speech input processing tasks may be specific to errors in children's speech output. Further research is required to develop our understanding of these skills in this population and any associations with speech output. WHAT THIS PAPER ADDS: What is already known on the subject Few studies have been published that examine aspects of speech input processing in children born with CP±L. Theoretical models of speech processing, and published studies, propose that speech input processing skills are associated with SSD in children who were not born with a cleft. However, it is less clear whether there is any association between speech input processing and cleft-related SSD. What this paper adds to existing knowledge This review systematically collates and evaluates the published, peer-reviewed evidence regarding speech input processing skills in children born with CP±L. The collated evidence indicates that some speech input processing skills differ between children with and without CP±L. There is some evidence, from a single study, that speech input processing of specific cleft speech characteristics (CSCs) may be associated with the presence of these CSCs in the speech output of some children born with CP±L. What are the potential or actual clinical implications of this work? While the evidence is currently limited, increasing our knowledge of speech input processing skills in children born with CP±L contributes to our clinical understanding of the nature of cleft-related SSD. The current evidence suggests that speech and language therapists should consider speech input processing skills when assessing children with cleft-related SSD to support intervention planning. Considering these skills in relation to literacy development in these children may also be important.

This article provides an overview of writing for publication in peer-reviewed journals. While the main focus is on writing a research article, it also provides guidance on factors influencing journal selection, including journal scope, intended audience for the findings, open access requirements, and journal citation metrics. Finally, it covers the standard content of a scientific journal article, providing general advice and guidance regarding the information researchers would typically include in their published papers.

Background To estimate the rate of occult cervical lymph node metastases in cN0 patients affected by primary parotid carcinomas and to scrutinize the evidence on the indication and extent of elective neck dissection in these neoplasms. Methods Medline, Embase, Web of Science, Cochrane Library and Scopus were searched until August 31, 2020, to identify studies reporting the use of elective neck dissection in the management of malignant parotid tumours. The PRISMA checklist was used. A single arm meta-analysis was then made to determine the pooled rate of occult lymph node metastases. Risk of bias of the included studies was assessed through the ROBINS-E tool. Results The initial search returned 20 541 articles, of which twelve met the inclusion criteria and were included in the meta-analysis. They comprised 1310 patients with parotid carcinoma, of whom 542 cN0 underwent elective neck dissection, which led to the diagnosis of lymph node metastasis (pN+/cN0) in 113 cases. Meta-analysis of the results of elective neck dissection showed an overall rate of occult metastases of 0.22 (99% CI: 0.14-0.30). Locally advanced or high-grade tumours were the commonest indications for elective neck dissection in the included studies. The most dissected lymph node levels were I-II-III, and level II was the commonest site of occult nodal metastases. Conclusions An occult metastasis rate of 0.22 (99% CI: 0.14-0.30) represents a not negligible percentage value, which should encourage further research to outline the most appropriate elective neck management in cN0 patients with parotid carcinomas.

IntroductionFrail older people are known to have low rates of advance care planning (ACP). Many frail patients prefer less aggressive treatment, but these preferences are often not known or respected. Frail patients often have multiple hospital admissions, potentially providing opportunities for ACP.ObjectiveTo systematically review the literature concerning ACP with frail older people in the acute hospital, with particular reference to: (1) Does ACP improve outcomes? (2) What are the views of patients, relatives and healthcare professionals regarding ACP? (3) Does ACP currently occur? (4) What are the facilitators and barriers to ACP?DesignSystematic literature review and narrative synthesis. Electronic search of MEDLINE, CINAHL, ASSIA, PsycINFO and Embase databases from January 1990 to May 2019 inclusive. Studies in the acute setting of populations with a mean age >75 years, not focused on a disease-specific terminal condition were included.Results16 133 articles were retrieved, 14 met inclusion criteria. No studies used an objective measure of frailty. One randomised controlled trial (RCT) found that ACP improves outcomes for older patients. Although 74%–84% of capacitous older inpatients are receptive to ACP, rates of ACP are 0%–5%; the reasons for this discrepancy have been little studied. The nature of ACP in clinical practice is unknown thus the extent to which it reflects the RCT intervention cannot be assessed. The outcomes that are important to patients are poorly understood and family and physician experiences have not been explored.ConclusionsA better understanding of this area could help to improve end-of-life care for frail older people.PROSPERO registration numberCRD42017080246.

Academic librarians with teaching responsibility have traditionally delivered training in discovering and organising information. However, in recent years, there has been an increased emphasis on supporting researchers through all stages of the research lifecycle. While librarians are ideally placed to provide training in writing for publication and presentation of research, very few in the United Kingdom appear to be doing so. However, there are clear benefits to teaching these subjects. Based on feedback from faculty on user needs, the University of Cambridge Medical Library's training programme was expanded to include training and support in the publication and presentation of research outputs. This article recounts the process by which the new courses were developed, and the techniques used by the library's teaching staff to gain understanding of conventions and requirements of forms of written communication with which they were unfamiliar. It also evaluates the impact of the new courses, discusses next steps and provides advice for other librarians wishing to develop similar courses. D.I.

BackgroundThe rising prevalence of childhood obesity is a global public health concern. Evidence suggests that exposure to non-parental childcare before age six years is associated with increased risk of obesity, diet, and activity behaviours (physical activity, sedentary behaviour, and sleep). However, findings are inconsistent and mostly from cross-sectional studies, making it difficult to identify the direction of causation in associations. This review identified and synthesised the published research on longitudinal associations between non-parental childcare during early childhood, diet, and activity behaviours.MethodsSeven databases were searched using a predefined search strategy. Results were independently double-screened through title/abstract and full-text stages according to predefined criteria. Included studies were tabulated, and evaluated for risk of bias using the Nutrition Evidence Library Bias Assessment Tool.ResultsOf 18793 references screened, 13 studies met eligibility criteria and were included in the review. Eight studies reported on diet and seven studies reported on activity behaviour outcomes (three on physical activity, three on sedentary behaviour, and one on sleep). These studies included results on 89 tested childcare:outcome associations. Of 63 associations testing diet outcomes, 37 (59%) were null, and the remainder showed inconsistent patterns. There was an indication of a potential benefit of Head Start providers (vs other care, including parental) on dietary behaviours. Of 26 associations testing activity behaviour outcomes, 22 (85%) were null, and the remainder were inconsistent. Most studies (92%) did not use (or did not report using) valid and reliable outcome measures, and outcome assessors were not blinded (or it was unclear if they were blinded) to children’s exposure status (77%).ConclusionsThe scarce available literature indicates little and mixed evidence of a longitudinal association between exposure to non-parental childcare before age six years and diet or activity behaviours. This reflects a paucity of research, rather than clear evidence of no effect. There is an urgent need for studies investigating the longitudinal associations of non-parental childcare on diet and activity behaviours to assess potential lasting effects and mechanisms. Studies should assess whether and how associations vary by provider and child sub-groups, as well as differences by intensity and duration of care.

This prospective cohort study describes associations between the presence of filaggrin gene mutations and eczema, rhinitis and wheeze from as early as age six months, raising new questions regarding underlying mechanisms and timing of interventions.

Background A significant proportion of the worldwide population is at risk of social isolation and loneliness as a result of the COVID-19 pandemic. We aimed to identify effective interventions to reduce social isolation and loneliness that are compatible with COVID-19 shielding and social distancing measures. Methods and findings In this rapid systematic review, we searched six electronic databases (Medline, Embase, Web of Science, PsycINFO, Cochrane Database of Systematic Reviews and SCOPUS) from inception to April 2020 for systematic reviews appraising interventions for loneliness and/or social isolation. Primary studies from those reviews were eligible if they included: 1) participants in a non-hospital setting; 2) interventions to reduce social isolation and/or loneliness that would be feasible during COVID-19 shielding measures; 3) a relevant control group; and 4) quantitative measures of social isolation, social support or loneliness. At least two authors independently screened studies, extracted data, and assessed risk of bias using the Downs and Black checklist. Study registration: PROSPERO CRD42020178654. We identified 45 RCTs and 13 non-randomised controlled trials; none were conducted during the COVID-19 pandemic. The nature, type, and potential effectiveness of interventions varied greatly. Effective interventions for loneliness include psychological therapies such as mindfulness, lessons on friendship, robotic pets, and social facilitation software. Few interventions improved social isolation. Overall, 37 of 58 studies were of “Fair” quality, as measured by the Downs & Black checklist. The main study limitations identified were the inclusion of studies of variable quality; the applicability of our findings to the entire population; and the current poor understanding of the types of loneliness and isolation experienced by different groups affected by the COVID-19 pandemic. Conclusions Many effective interventions involved cognitive or educational components, or facilitated communication between peers. These interventions may require minor modifications to align with COVID-19 shielding/social distancing measures. Future high-quality randomised controlled trials conducted under shielding/social distancing constraints are urgently needed.

Background The rising prevalence of obesity, particularly in childhood, is a global public health emergency. There is some evidence that exposure to non-parental childcare before age 6 years is associated with subsequent development of obesity and obesity-related behaviours such as physical activity, sedentary behaviour, sleep, diet and stress, although these findings are inconsistent. It is possible that the relationship between early childcare and later obesity and obesity-related behaviours depends on characteristics of childcare exposure such as type (i.e. informal versus formal care), duration (i.e. number of years spent in childcare), intensity (e.g. number of hours per week) and timing (i.e. age of onset of childcare) of care received. The relationship may also be moderated by socio-demographic characteristics of children and their families. We will conduct a systematic review exploring longitudinal associations between childcare (type, duration, intensity and timing) and measures of adiposity and body mass, physical activity, sedentary behaviour, sleep, diet and stress. We will also assess whether these relationships vary by socio-demographic factors. Methods We will include studies that explore longitudinal associations between childcare attendance in children aged

Cadmium (Cd+2) has been shown to transiently increase the expression of mRNA for the third isoform of the metallothionein (MT-3) gene family in cultured human proximal tubule (HPT) cells. The goal of the present study was to further define the expression of MT-3 in mortal (HPT) and immortal (HK-2) cultures of HPT cells when exposed to lethal and sub-lethal concentrations of Cd+2 under both acute and chronic time periods of exposure. Expression of MT-3 mRNA and protein was determined in cultured HPT cells and HK-2 cells using reverse-transcription-polymerase chain reaction (RT-PCR) and immuno-blotting, and expression of c-fos, c-jun and c-myc mRNA by RT-PCR. The results confirmed that exposure of the HPT cells to Cd+2 induced a transient increase in MT-3 mRNA and extended the induction to include a subsequent transient increase in the level of the MT-3 protein. The induction of MT-3 was rapid and returned to control values within 48 h of exposure despite the continued presence of lethal and sublethal concentrations of Cd+2. It was also demonstrated that the pattern of expression of MT-3 mRNA was similar to that of the early response genes, c-fos, c-jun and c-myc. It was shown that the HK-2 cells did not express MT-3 when exposed to Cd+2, but had similar expression of the c-fos, c-jun and c-myc genes. The results demonstrate that MT-3 expression is metal responsive in HPT cells.