Complement Regulates Nutrient Influx and Metabolic Reprogramming during Th1 Cell Responses.

Expansion and acquisition of Th1 cell effector function requires metabolic reprogramming; however, the signals instructing these adaptations remain poorly defined. Here we found that in activated human T cells, autocrine stimulation of the complement receptor CD46, and specifically its intracellular domain CYT-1, was required for induction of the amino acid (AA) transporter LAT1 and enhanced expression of the glucose transporter GLUT1. Furthermore, CD46 activation simultaneously drove expression of LAMTOR5, which mediated assembly of the AA-sensing Ragulator-Rag-mTORC1 complex and increased glycolysis and oxidative phosphorylation (OXPHOS), required for cytokine production. T cells from CD46-deficient patients, characterized by defective Th1 cell induction, failed to upregulate the molecular components of this metabolic program as well as glycolysis and OXPHOS, but IFN-γ production could be reinstated by retrovirus-mediated CD46-CYT-1 expression. These data establish a critical link between the complement system and immunometabolic adaptations driving human CD4(+) T cell effector function.

Improving domestic violence screening practices in the emergency department: an Australian perspective.

INTRODUCTION: Domestic violence (DV) is a major cause of morbidity worldwide. The ED is a location recommended for opportunistic screening. However, screening within EDs remains irregular. OBJECTIVE: To examine intrinsic and extrinsic barriers to routine screening in Australian EDs, while describing actions taken after identification of DV. METHODS: Emergency clinicians at nine public hospitals participated in an anonymous online survey. Factor analysis was performed to identify principal components around attitudes and beliefs towards screening. RESULTS: In total, 496 emergency clinicians participated. Universal screening was uncommon; less than 2% of respondents reported screening all adults or all women. Although willing, nearly half (45%) reported not knowing how to screen. High patient load and no single rooms were 'very or severely limiting' for 88% of respondents, respectively, while 24/7 social work and interpreter services, and online/written DV protocols were top enablers. Factor analysis identified four distinct intrinsic belief components: (1) screening is not futile and could be done in ED, (2) screening will not cause harm, (3) there is a duty to screen and (4) I am willing to screen. CONCLUSION: This study describes a culture of Queensland ED clinicians that believe DV screening in ED is important and interventions are effective. Most ED clinicians are willing to screen. In this setting, availability of social work and interpreter services are important mitigating resources. Clinician education focusing on duty to screen, coupled with a built-in screening tool, and e-links to a local management protocol may improve the uptake of screening and subsequently increase detection.

The effectiveness of hand hygiene interventions for preventing community transmission or acquisition of novel coronavirus or influenza infections: a systematic review.

BACKGROUND: Novel coronaviruses and influenza can cause infection, epidemics, and pandemics. Improving hand hygiene (HH) of the general public is recommended for preventing these infections. This systematic review examined the effectiveness of HH interventions for preventing transmission or acquisition of such infections in the community. METHODS: PubMed, MEDLINE, CINAHL and Web of Science databases were searched (January 2002-February 2022) for empirical studies related to HH in the general public and to the acquisition or transmission of novel coronavirus infections or influenza. Studies on healthcare staff, and with outcomes of compliance or absenteeism were excluded. Study selection, data extraction and quality assessment, using the Cochrane Effective Practice and Organization of Care risk of bias criteria or Joanna Briggs Institute Critical Appraisal checklists, were conducted by one reviewer, and double-checked by another. For intervention studies, effect estimates were calculated while the remaining studies were synthesised narratively. The protocol was pre-registered (PROSPERO 2020: CRD42020196525). RESULTS: Twenty-two studies were included. Six were intervention studies evaluating the effectiveness of HH education and provision of products, or hand washing against influenza. Only two school-based interventions showed a significant protective effect (OR: 0.64; 95% CI 0.51, 0.80 and OR: 0.40; 95% CI 0.22, 0.71), with risk of bias being high (n = 1) and unclear (n = 1). Of the 16 non-intervention studies, 13 reported the protective effect of HH against influenza, SARS or COVID-19 (P < 0.05), but risk of bias was high (n = 7), unclear (n = 5) or low (n = 1). However, evidence in relation to when, and how frequently HH should be performed was inconsistent. CONCLUSIONS: To our knowledge, this is the first systematic review of effectiveness of HH for prevention of community transmission or acquisition of respiratory viruses that have caused epidemics or pandemics, including SARS-CoV-1, SARS-CoV-2 and influenza viruses. The evidence supporting the protective effect of HH was heterogeneous and limited by methodological quality; thus, insufficient to recommend changes to current HH guidelines. Future work is required to identify in what circumstances, how frequently and what product should be used when performing HH in the community and to develop effective interventions for promoting these specific behaviours in communities during epidemics.

Using conjoint analysis to measure the importance of psychosocial traits in the choices of bladder management after spinal cord injury.

OBJECTIVE: To conduct a conjoint analysis experiment to better understand the psychosocial priorities related to bladder management in individuals after spinal cord injury (SCI). METHODS: We developed a conjoint analysis survey that included 11 psychosocial attributes phrased in the context of bladder management (including attributes for urinary infections, and incontinence). We then performed a multi-center prospective cross-sectional study of adults with existing SCI which consisted of a baseline interview, followed by the online conjoint analysis survey (delivered through Sawtooth software). Hierarchical Bayes random effects regression analysis was used to determine the relative importance of the attributes. RESULTS: A total of 345 people complete the study. There was good representation of both men and women, and individuals with cervical and thoracic or lower lesions. The most important attribute was the frequency of urinary infections. Age, sex, and level of SCI were generally not related to the attributes measured in the study. In the subgroup of 256 patients who used a catheter for bladder management, significantly more importance was placed on urinary tract infections, time, fluid intake, and social life among indwelling catheter users compared to intermittent catheter users. CONCLUSIONS: Most bladder-related psychosocial priorities are not impacted by a patient's age, sex or level of SCI. Differences in psychosocial priorities between indwelling and intermittent catheter users may represent factors that should be focused on to optimize bladder management after SCI.

Barriers and enablers of implementation of alcohol guidelines with pregnant women: a cross-sectional survey among UK midwives.

BACKGROUND: In 2016, the UK Chief Medical Officers revised their guidance on alcohol and advised women to abstain from alcohol if pregnant or planning pregnancy. Midwives have a key role in advising women about alcohol during pregnancy. The aim of this study was to investigate UK midwives' practices regarding the 2016 Chief Medical Officers Alcohol Guidelines for pregnancy, and factors influencing their implementation during antenatal appointments. METHODS: Online cross-sectional survey of a convenience sample of UK midwives recruited through professional networks and social media. Data were gathered using an anonymous online questionnaire addressing knowledge of the 2016 Alcohol Guidelines for pregnancy; practice behaviours regarding alcohol assessment and advice; and questions based on the Theoretical Domains Framework (TDF) to evaluate implementation of advising abstinence at antenatal booking and subsequent antenatal appointments. RESULTS: Of 842 questionnaire respondents, 58% were aware of the 2016 Alcohol Guidelines of whom 91% (438) cited abstinence was recommended, although 19% (93) cited recommendations from previous guidelines. Nonetheless, 97% of 842 midwives always or usually advised women to abstain from alcohol at the booking appointment, and 38% at subsequent antenatal appointments. Mean TDF domain scores (range 1-7) for advising abstinence at subsequent appointments were highest (indicative of barriers) for social influences (3.65 sd 0.84), beliefs about consequences (3.16 sd 1.13) and beliefs about capabilities (3.03 sd 073); and lowest (indicative of facilitators) for knowledge (1.35 sd 0.73) and professional role and identity (1.46 sd 0.77). Logistic regression analysis indicated that the TDF domains: beliefs about capabilities (OR = 0.71, 95% CI: 0.57, 0.88), emotion (OR = 0.78; 95%CI: 0.67, 0.90), and professional role and identity (OR = 0.69, 95%CI 0.51, 0.95) were strong predictors of midwives advising all women to abstain from alcohol at appointments other than at booking. CONCLUSIONS: Our results suggest that skill development and reinforcement of support from colleagues and the wider maternity system could support midwives' implementation of alcohol advice at each antenatal appointment, not just at booking could lead to improved outcomes for women and infants. Implementation of alcohol care pathways in maternity settings are beneficial from a lifecourse perspective for women, children, families, and the wider community.

A qualitative assessment of psychosocial aspects that play a role in bladder management after spinal cord injury.

STUDY DESIGN: Prospective qualitative study using semi-structured, open-ended interviews. OBJECTIVES: To better understand psychosocial aspects of bladder management after spinal cord injury (SCI). SETTING: People with SCI, recruited through three tertiary care centres in North America. METHODS: Thirty-four community-dwelling individuals with SCI were selected using purposive sampling to ensure men and women with both tetraplegia and paraplegia were represented. The interviews were audio recorded and transcribed. NVivo software was used to code psychosocial domains, medical complications, and methods of bladder management. A qualitative interpretive approach was used, and four participants participated in a debrief session to review the study findings. RESULTS: The median age was 49 (IQR 40-62) years and 61% (21/34) were male. Most had complete injuries (AIS A, 47%, 16/34), and most had a cervical lesion (56%, 19/34). There was a large range of time living with a SCI (median 20 years, IQR 9-31), and most participants managed their bladder with intermittent catheterisation (67% 23/34). The five most common psychosocial domains were anxiety (often in the context of urinary infections, incontinence, or not being able to catheterise), loss of control (due to irregular bladder behaviour), and embarrassment (from incontinence occurring in public); the domains of confidence and independence/planning included both positive and negative examples of bladder management experiences. CONCLUSIONS: This study demonstrated consistent psychosocial topics related to bladder management in people living with SCI. This information will help counsel people regarding bladder management and identify areas for education and optimisation of bladder function from a psychosocial perspective.

What matters to people with memory problems, healthy volunteers and health and social care professionals in the context of developing treatment to prevent Alzheimer's dementia? A qualitative study.

BACKGROUND: Alzheimer's disease (AD) is recognized as one of the greatest global public health challenges. There is increasing consensus that optimal disease modification using pharmaceuticals may best be achieved earlier in the disease continuum before symptoms occur. However, more needs to be understood about what outcomes are meaningful to potential participants in clinical trials within this preventative paradigm and how people make trade-offs between risks and benefits. The Electronic Person-Specific Outcome Measure (ePSOM) programme is developing an app to capture person-specific outcomes and preferences in clinical trials. OBJECTIVE: As one phase in the ePSOM programme, this study explored what matters when developing new treatments to prevent AD and how trade-offs are made between risks and benefits, from three perspectives. DESIGN: Focus groups were conducted with people living with memory problems (n = 21) and healthy volunteers (n = 10), and telephone interviews with health and social care professionals (n = 10). Differences and overlap between the three groups were explored. RESULTS: Outcomes that matter lie in five key domains in relation to what matters in everyday life: Everyday Functioning; Relationships and Social Connections; Enjoying Life; Sense of Identity; and Alleviating  Symptoms. Insights were gained into the significance of reducing the risk of developing dementia with drugs and the processes of weighing up risks versus benefits. DISCUSSION AND CONCLUSIONS: The key domains identified are being used to inform the next stage of the ePSOM programme which is to develop a survey to be distributed nationally in the UK to explore these issues further.

A systematic review and meta-analysis in the effectiveness of mobile phone interventions used to improve adherence to antiretroviral therapy in HIV infection.

BACKGROUND: Antiretroviral therapy is effective in preventing the progression of HIV to AIDS, but adherence to HIV medication is lower than ideal. A previous Cochrane review concluded that SMS interventions increased adherence to HIV medication, but more recent trials have reported mixed results. Our review aims to provide an up-to-date synthesis of the effects of interventions delivered by mobile phone on adherence. METHODS: We searched Cochrane, Medline, CINAHL, EMBASE and Global Health for randomised control trials (RCTs) of interventions delivered by mobile phones, designed to increase adherence to antiretroviral medication. Risk of bias was assessed using the Cochrane risk of bias tool. We calculated relative risk ratios (RR) or standardised mean difference (SMD) with 95% confidence interval (CI). Trials were analysed depending on delivery mechanism and intervention characteristics. We conducted meta-analysis for primary objective outcome measures. RESULTS: We identified 19 trials. No trials were at low risk of bias. Interventions were delivered as follows; nine via text message, five via mobile phone call, one via mobile phone imagery and four via mixed interventions. There was no effect when interventions delivered by text message were pooled in the RR1.25 (CI 0.97 to 1.61) P = 0.08. The SMD 0.42 (0.03 to 0.81) p = 0.04 showed a moderate effect to improve adherence. There was mixed evidence of the effect of text messages delivered daily, weekly, at scheduled or triggered times, however, messages with link to support, interactivity and three or more behavior change techniques (BCTs) all improved adherence. Of the five trials delivered by mobile phone call, one reported a reduction in HIV viral load. One trial using mobile phone imagery reported a reduction in HIV viral load. Three trials that delivered interventions by text message and mobile phone counselling reported improved biological outcomes. CONCLUSION: Specific interventions, of proven effectiveness should be considered for implementation, rather than mobile phone-based interventions in general. Interventions targeting a wider range of barriers to adherence may be more effective than existing interventions. The effects and cost-effectiveness of such interventions should be evaluated in a randomised controlled trial alongside long term objective and clinically important outcomes.

Visceral Leishmaniasis in Traveler to Guyana Caused by Leishmania siamensis, London, UK.

The parasite Leishmania siamensis is a zoonotic agent of leishmaniasis; infection in animals has been documented in Europe and the United States. Reported authochthonous human infections have been limited to Thailand. We report a case of human visceral Leishmania siamensis infection acquired in Guyana, suggesting colonization in South America.

A new highly sensitive enzyme-linked immunosorbent assay for the detection of Plasmodium falciparum histidine-rich protein 2 in whole blood.

BACKGROUND: The detection of submicroscopic infections in low prevalence settings has become an increasingly important challenge for malaria elimination strategies. The current field rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria are inadequate to detect low-density infections. Therefore, there is a need to develop more sensitive field diagnostic tools. In parallel, a highly sensitive laboratory reference assay will be essential to evaluate new diagnostic tools. Recently, the highly sensitive Alere™ Malaria Ag P.f ELISA (HS ELISA) was developed to detect P. falciparum histidine-rich protein 2 (HRP2) in clinical whole blood specimens. In this study, the analytical and clinical performance of the HS ELISA was determined using recombinant P. falciparum HRP2, P. falciparum native culture parasites, and archived highly pedigreed clinical whole blood specimens from Karen village, Myanmar and Nagongera, Uganda. RESULTS: The HS ELISA has an analytical sensitivity of less than 25 pg/mL and shows strong specificity for P. falciparum HRP2 when tested against P. falciparum native culture strains with pfhrp2 and pfhrp3 gene deletions. Additionally, the Z'-factor statistic of 0.862 indicates the HS ELISA as an excellent, reproducible assay, and the coefficients of variation for inter- and intra-plate testing, 11.76% and 2.51%, were acceptable. Against clinical whole blood specimens with concordant microscopic and PCR results, the HS ELISA showed 100% (95% CI 96.4-100) diagnostic sensitivity and 97.9% (95% CI 94.8-99.4) diagnostic specificity. For P. falciparum positive specimens with HRP2 concentrations below 400 pg/mL, the sensitivity and specificity were 100% (95% CI 88.4-100) and 88.9% (95% CI 70.8-97.6), respectively. The overall sensitivity and specificity for all 352 samples were 100% (CI 95% 96-100%) and 97.3% (CI 95% 94-99%). CONCLUSIONS: The HS ELISA is a robust and reproducible assay. The findings suggest that the HS ELISA may be a useful tool as an affordable reference assay for new ultra-sensitive HRP2-based RDTs.

A Seat Around the Table: Participatory Data Analysis With People Living With Dementia.

The involvement of "people with experience" in research has developed considerably in the last decade. However, involvement as co-analysts at the point of data analysis and synthesis has received very little attention-in particular, there is very little work that involves people living with dementia as co-analysts. In this qualitative secondary data analysis project, we (a) analyzed data through two theoretical lenses: Douglas's cultural theory of risk and Tronto's Ethic of Care, and (b) analyzed data in workshops with people living with dementia. The design involved cycles of presenting, interpreting, representing and reinterpreting the data, and findings between multiple stakeholders. We explore ways of involving people with experience as co-analysts and explore the role of reflexivity, multiple voicing, literary styling, and performance in participatory data analysis.

Does targeting children with hygiene promotion messages work? The effect of handwashing promotion targeted at children, on diarrhoea, soil-transmitted helminth infections and behaviour change, in low- and middle-income countries.

OBJECTIVES: To synthesise evidence on the effect of handwashing promotion interventions targeting children, on diarrhoea, soil-transmitted helminth infection and handwashing behaviour, in low- and middle-income country settings. METHODS: A systematic review of the literature was performed by searching eight databases, and reference lists were hand-searched for additional articles. Studies were reviewed for inclusion according to pre-defined inclusion criteria and the quality of all studies was assessed. RESULTS: Eight studies were included in this review: seven cluster-randomised controlled trials and one cluster non-randomised controlled trial. All eight studies targeted children aged 5-12 attending primary school but were heterogeneous for both the type of intervention and the reported outcomes so results were synthesised qualitatively. None of the studies were of high quality and the large majority were at high risk of bias. The reported effect of child-targeted handwashing interventions on our outcomes of interest varied between studies. Of the different interventions reported, no one approach to promoting handwashing among children appeared most effective. CONCLUSION: Our review found very few studies that evaluated handwashing interventions targeting children and all had various methodological limitations. It is plausible that interventions which succeed in changing children's handwashing practices will lead to significant health impacts given that much of the attributable disease burden is concentrated in that age group. The current paucity of evidence in this area, however, does not permit any recommendations to be made as to the most effective route to increasing handwashing with soap practice among children in LMIC.

Fixing the broken image of care homes, could a 'care home innovation centre' be the answer?

The UK has many excellent care homes that provide high-quality care for their residents; however, across the care home sector, there is a significant need for improvement. Even though the majority of care homes receive a rating of 'good' from regulators, still significant numbers are identified as requiring 'improvement' or are 'inadequate'. Such findings resonate with the public perceptions of long-term care as a negative choice, to be avoided wherever possible-as well as impacting on the career choices of health and social care students. Projections of current demographics highlight that, within 10 years, the part of our population that will be growing the fastest will be those people older than 80 years old with the suggestion that spending on long-term care provision needs to rise from 0.6% of our Gross Domestic Product in 2002 to 0.96% by 2031. Teaching/research-based care homes have been developed in the USA, Canada, Norway, the Netherlands and Australia in response to scandals about care, and the shortage of trained geriatric healthcare staff. There is increasing evidence that such facilities help to reduce inappropriate hospital admissions, increase staff competency and bring increased enthusiasm about working in care homes and improve the quality of care. Is this something that the UK should think of developing? This commentary details the core goals of a Care Home Innovation Centre for training and research as a radical vision to change the culture and image of care homes, and help address this huge public health issue we face.

Stress-activated Dendritic Cells (DC) Induce Dual Interleukin (IL)-15- and IL1ß-mediated Pathways, Which May Elicit CD4+ Memory T Cells and Interferon (IFN)-stimulated Genes.

The prevailing evidence suggests that immunological memory does not require antigenic re-stimulation but is maintained by low level tonic stimulation. We examined the hypothesis that stress agents contribute to tonic cellular activation and maintain immunological memory. Stimulation of monocyte-derived dendritic cells (DC) with stress agents elicits reactive oxygen species and HSP70. NFκB is activated, which up-regulates membrane-associated (ma) IL-15, caspase-1 and IL-1ß. Co-culture of stress-treated DC with mononuclear cells activates IL-15 and IL-1ß receptors on CD4(+) T cells, eliciting CD40L, proliferation, and up-regulation of CD45RO(+) memory T cells. The transcription factors Tbet(high) and RORγt are up-regulated, whereas FoxP3 is down-regulated, resulting in enhanced Th1 and Th17 expression and the corresponding cytokines. The interaction between maIL-15 expressed by DC and IL-15R on CD4(+) T cells results in one pathway and the corresponding cells expressing IL-1ß and IL1ßR as a second pathway. Importantly, inhibition studies with IL-15 antibodies and IL-1ßR inhibitor suggest that both pathways may be required for optimum CD4(+) CD45RO(+) memory T cell expression. Type 1 IFN expression in splenic CD11c DC of stress-treated mice demonstrated a significant increase of IFN-α in CD11c CD317(+) and CD8α(+) DC. Analysis of RNA in human CD4(+) memory T cells showed up-regulation of type 1 IFN-stimulated genes and inhibition with histone methyltransferase inhibitor. We suggest the paradigm that stress-induced tonic stimulation might be responsible for the robust persistence of the immune response in vaccination and that epigenetic changes are involved in maintaining CD4(+) T cell memory.

Responsive versus scheduled feeding for preterm infants.

BACKGROUND: Feeding preterm infants in response to their hunger and satiation cues (responsive, cue-based, or infant-led feeding) rather than at scheduled intervals might enhance infants' and parents' experience and satisfaction, help in the establishment of independent oral feeding, increase nutrient intake and growth rates, and allow earlier hospital discharge. OBJECTIVES: To assess the effect of a policy of feeding preterm infants on a responsive basis versus feeding prescribed volumes at scheduled intervals on growth rates, levels of parent satisfaction, and time to hospital discharge. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE via PubMed (1966 to 17 February 2016), Embase (1980 to 17 February 2016), and CINAHL (1982 to 17 February 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs that compared a policy of feeding preterm infants on a responsive basis versus feeding at scheduled intervals. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. We analysed the treatment effects in the individual trials and reported the risk ratio and risk difference for dichotomous data and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses. We assessed the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We found nine eligible RCTs including 593 infants in total. These trials compared responsive with scheduled interval regimens in preterm infants in the transition phase from intragastric tube to oral feeding. The trials were generally small and contained various methodological weaknesses including lack of blinding and incomplete assessment of all randomised participants. Meta-analyses, although limited by data quality and availability, suggest that responsive feeding results in slightly slower rates of weight gain (MD -1.36, 95% CI -2.44 to -0.29 g/kg/day), and provide some evidence that responsive feeding reduces the time taken for infants to transition from enteral tube to oral feeding (MD -5.53, 95% CI -6.80 to -4.25 days). GRADE assessments indicated low quality of evidence. The importance of this finding is uncertain as the trials did not find a strong or consistent effect on the duration of hospitalisation. None of the included trials reported any parent, caregiver, or staff views. AUTHORS' CONCLUSIONS: Overall, the data do not provide strong or consistent evidence that responsive feeding affects important outcomes for preterm infants or their families. Some (low quality) evidence exists that preterm infants fed in response to feeding and satiation cues achieve full oral feeding earlier than infants fed prescribed volumes at scheduled intervals. This finding should be interpreted cautiously because of methodological weaknesses in the included trials. A large RCT would be needed to confirm this finding and to determine if responsive feeding of preterm infants affects other important outcomes.

Responsive versus scheduled feeding for preterm infants.

BACKGROUND: Feeding preterm infants in response to their hunger and satiation cues (responsive, cue-based, or infant-led feeding) rather than at scheduled intervals might enhance infants' and parents' experience and satisfaction, help in the establishment of independent oral feeding, increase nutrient intake and growth rates, and allow earlier hospital discharge. OBJECTIVES: To assess the effect of feeding preterm infants on a responsive basis versus feeding prescribed volumes at scheduled intervals on growth, duration of hospital stay, and parental satisfaction. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 9, 2015), MEDLINE (1966 to September 2015), EMBASE (1980 to September 2015), and CINAHL (1982 to September 2015), conference proceedings, previous reviews, and trial registries. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs that compared a policy of feeding preterm infants on a responsive basis versus feeding at scheduled intervals. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. We analysed the treatment effects in the individual trials and reported the risk ratio and risk difference for dichotomous data and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses. MAIN RESULTS: We found nine eligible RCTs including 593 infants in total. These trials compared responsive with scheduled interval regimens in preterm infants in the transition phase from intragastric tube to oral feeding. The trials were generally small and contained various methodological weaknesses including lack of blinding and incomplete assessment of all randomised participants. Meta-analyses, although limited by data quality and availability, suggest that responsive feeding results in slightly slower rates of weight gain (MD -1.4, 95% CI -2.4 to -0.3 g/kg/day), and provide some evidence that responsive feeding reduces the time taken for infants to transition from enteral tube to oral feeding (MD -5.5, 95% CI -6.8 to -4.2 days). The importance of this finding is uncertain as the trials did not find a strong or consistent effect on the duration of hospitalisation. None of the included trials reported any parent, caregiver, or staff views. AUTHORS' CONCLUSIONS: Overall, the data do not provide strong or consistent evidence that responsive feeding affects important outcomes for preterm infants or their families. Some evidence exists that preterm infants fed in response to feeding and satiation cues achieve full oral feeding earlier than infants fed prescribed volumes at scheduled intervals. However, this finding should be interpreted cautiously because of methodological weaknesses in the included trials. A large RCT would be needed to confirm this finding and to determine if responsive feeding of preterm infants affects other important outcomes.

Initial development of the Symptom Screening in Pediatrics Tool (SSPedi).

BACKGROUND: We previously identified published scales for symptom assessment in pediatric cancer patients. The objectives of this study were to identify if any of these scales were suitable for use or adaptation as a self-report symptom screening tool, and if not, to begin the process of creating a new tool. METHODS: A focus group of ten healthcare professionals with expertise in pediatric cancer symptom management and a patient advocate were convened. First, the group identified the optimal properties of a symptom screening tool for pediatric cancer patients. Next, the previously identified symptom assessment scales were evaluated against these properties. As none of the existing scales were adequate for symptom screening, a nominal group technique was used to identify the most important symptoms for inclusion in a new symptom screening tool. RESULTS: Optimal properties of a symptom screening tool included minimal respondent burden, inclusion of 15 items or less, and inclusion of the most burdensome symptoms. None of the previously identified scales were adequate because they lacked content validity and were too long or would be too hard for children to understand. Nominal group technique identified 15 items to be included; an initial draft was developed and named the Symptom Screening in Pediatrics (SSPedi) Tool. CONCLUSIONS: This study identified the lack of an appropriate symptom screening tool for use by pediatric cancer patients. A preliminary version of SSPedi was developed. Subsequent work will ensure that it is understandable by children and evaluate its psychometric properties.

Clinical evaluation of a loop-mediated amplification kit for diagnosis of imported malaria.

BACKGROUND: Diagnosis of malaria relies on parasite detection by microscopy or antigen detection; both fail to detect low-density infections. New tests providing rapid, sensitive diagnosis with minimal need for training would enhance both malaria diagnosis and malaria control activities. We determined the diagnostic accuracy of a new loop-mediated amplification (LAMP) kit in febrile returned travelers. METHODS: The kit was evaluated in sequential blood samples from returned travelers sent for pathogen testing to a specialist parasitology laboratory. Microscopy was performed, and then malaria LAMP was performed using Plasmodium genus and Plasmodium falciparum-specific tests in parallel. Nested polymerase chain reaction (PCR) was performed on all samples as the reference standard. Primary outcome measures for diagnostic accuracy were sensitivity and specificity of LAMP results, compared with those of nested PCR. RESULTS: A total of 705 samples were tested in the primary analysis. Sensitivity and specificity were 98.4% and 98.1%, respectively, for the LAMP P. falciparum primers and 97.0% and 99.2%, respectively, for the Plasmodium genus primers. Post hoc repeat PCR analysis of all 15 tests with discrepant results resolved 4 results in favor of LAMP, suggesting that the primary analysis had underestimated diagnostic accuracy. CONCLUSIONS: Malaria LAMP had a diagnostic accuracy similar to that of nested PCR, with a greatly reduced time to result, and was superior to expert microscopy.

Practicalities of promoting practice-based learning in end of life care for care home staff: Lessons from "online" supportive conversations and reflection sessions.

INTRODUCTION: Deaths in care homes and "at home" are anticipated to account for a third of UK deaths by 2040. Currently, palliative and end of life care are not part of statutory training in care homes. Reflective practice is a tool that can facilitate practice-based learning and support. Following a feasibly study to test "online" supportive conversations and reflection sessions (OSCaRS) to support care home staff in relation to death/dying during the first months of the COVID pandemic, a one-year practice development follow-up project was undertaken with the aim to create a team of NHS/specialist palliative care (SPC)-based facilitators to lead and support OSCaRS provision in up to 50 care homes in one region in Scotland-the focus of this paper. METHODS: Forty care home managers attended an on-line session explaining the project, with a similar session held for 19 NHS/SPC-based nurses external to care homes. Those interested in facilitating OSCaRS then attended three education sessions. DATA COLLECTED: records of all activities; reflective notes on OSCaRS organised/delivered; a summary of each OSCaRS reflection/learning points; final interviews with NHS/SPC trainee facilitators. RESULTS: A total of 19 NHS/SPC facilitators delivered one or more OSCaRS in 22 participating care homes. However, as of January 2022 only six trained facilitators remained active. Out of the 158 OSCaRS arranged, 96 took place with a total of 262 staff attending. There were three important aspects that emerged: the role, remit, and resources of NHS/SPC supporting OSCaRS; requirements within care homes for establishing OSCaRS; and, the practice-based learning topics discussed at each OSCaRS. CONCLUSION: Attempts to establish a team of NHS/SPC facilitators to lead OSCaRS highlights that end of life care education in care homes does not clearly fall within the contractual remit of either group or risks being missed due to more pressing priorities.

Transpyloric versus gastric tube feeding for preterm infants.

BACKGROUND: Enteral feeding tubes for preterm infants may be placed in the stomach (gastric tube feeding) or in the upper small bowel (transpyloric tube feeding). There are potential advantages and disadvantages to both routes. OBJECTIVES: To determine the effect of feeding via the transpyloric route versus feeding via the gastric route on feeding tolerance, growth and development, and adverse consequences (death, gastro-intestinal disturbance including necrotising enterocolitis, aspiration pneumonia, chronic lung disease, pyloric stenosis) in preterm infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (The Cochrane Library 2012, Issue 3), MEDLINE, EMBASE, and CINAHL (to June 2012), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing transpyloric with gastric tube feeding in preterm infants. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical risk ratio (RR), risk difference (RD), and mean difference (MD). MAIN RESULTS: We found nine eligible trials in which a total of 359 preterm infants participated. All of the trials contained methodological weaknesses with lack of allocation concealment, absence of blinding of caregivers or assessors, and incomplete follow-up being the major potential sources of bias. The included trials did not detect any statistically significant effects on feeding tolerance or in-hospital growth rates. Meta-analyses found that infants allocated to receive transpyloric feeding had a higher risk of gastro-intestinal disturbance (typical RR 1.48 (95% confidence interval (CI) 1.05 to 2.09); typical RD 0.09 (95% CI 0.02 to 0.17); number needed to treat for an additional harmful outcome (NNTH) 10 (95% CI 6 to 50); six studies, 245 infants) and all-case mortality (typical RR 2.46 (95% CI 1.36 to 4.46); typical RD 0.16 (95% CI 0.07 to 0.26); NNTH 6 (95% CI 4 to 14); six studies, 217 infants). However, the trial that contributed most weight to these findings was likely to have been affected by selective allocation of the less mature and sicker infants to transpyloric feeding. We did not find any statistically significant differences in the incidence of other adverse events, including necrotising enterocolitis, intestinal perforation, and aspiration pneumonia. AUTHORS' CONCLUSIONS: The available data do not provide evidence of any beneficial effect of transpyloric feeding for preterm infants. Some evidence of harm exists, including a higher risk of gastrointestinal disturbance and mortality, but these findings should be interpreted and applied cautiously because of methodological weaknesses in the included trials.