The effect of care provided by paediatric critical care transport teams on mortality of children transported to paediatric intensive care units in England and Wales: a retrospective cohort study.

BACKGROUND: Centralisation of paediatric intensive care units (PICUs) has the increased the need for specialist paediatric critical care transport teams (PCCT) to transport critically ill children to PICU. We investigated the impact of care provided by PCCTs for children on mortality and other clinically important outcomes. METHODS: We analysed linked national data from the Paediatric Intensive Care Audit Network (PICANet) from children admitted to PICUs in England and Wales (2014-2016) to assess the impact of who led the child's transport, whether prolonged stabilisation by the PCCT was detrimental and the impact of critical incidents during transport on patient outcome. We used logistic regression models to estimate the adjusted odds and probability of mortality within 30 days of admission to PICU (primary outcome) and negative binomial models to investigate length of stay (LOS) and length of invasive ventilation (LOV). RESULTS: The study included 9112 children transported to PICU. The most common diagnosis was respiratory problems; junior doctors led the PCCT in just over half of all transports; and the 30-day mortality was 7.1%. Transports led by Advanced Nurse Practitioners and Junior Doctors had similar outcomes (adjusted mortality ANP: 0.035 versus Junior Doctor: 0.038). Prolonged stabilisation by the PCCT was possibly associated with increased mortality (0.059, 95% CI: 0.040 to 0.079 versus short stabilisation 0.044, 95% CI: 0.039 to 0.048). Critical incidents involving the child increased the adjusted odds of mortality within 30 days (odds ratio: 3.07). CONCLUSIONS: Variations in team composition between PCCTs appear to have little effect on patient outcomes. We believe differences in stabilisation approaches are due to residual confounding. Our finding that critical incidents were associated with worse outcomes indicates that safety during critical care transport is an important area for future quality improvement work

Differences in access to Emergency Paediatric Intensive Care and care during Transport (DEPICT): study protocol for a mixed methods study.

INTRODUCTION: Following centralisation of UK paediatric intensive care, specialist retrieval teams were established who travel to general hospitals to stabilise and transport sick children to regional paediatric intensive care units (PICUs). There is national variation among these PICU retrieval teams (PICRTs) in terms of how quickly they reach the patient's bedside and in the care provided during transport. The impact of these variations on clinical outcomes and the experience of stakeholders (patients, families and healthcare staff) is however unknown. The primary objective of this study is to address this evidence gap. METHODS AND ANALYSIS: This mixed-methods project involves the following: (1) retrospective analysis of linked data from routine clinical audits (2014-2016) to assess the impact of service variations on 30-day mortality and other secondary clinical outcomes; (2) a prospective questionnaire study conducted at 24 PICUs and 9 associated PICRTs in England and Wales over a 12-month period in 2018 to collect experience data from parents of transported children as well as qualitative analysis of in-depth interviews with a purposive sample of patients, parents and staff to assess the impact of service variations on patient/family experience; (3) health economic evaluation analysing transport service costs (and other associated costs) against lives saved and longer term measurements of quality of life at 12 months in transported children and (4) mathematical modelling evaluating the costs and potential impact of different service configurations. A final work stream involves a series of stakeholder workshops to synthesise study findings and generate recommendations. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Health Research Authority, ref: 2 18 569. Study results will be actively disseminated through peer-reviewed journals, conference presentations, social media, print and broadcast media, the internet and stakeholder workshops

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

New Australian guidelines for the treatment of alcohol problems: an overview of recommendations

Summary of recommendations and levels of evidence Chapter 2: Screening and assessment for unhealthy alcohol use Screening Screening for unhealthy alcohol use and appropriate interventions should be implemented in general practice (Level A), hospitals (Level B), emergency departments and community health and welfare settings (Level C). Quantity–frequency measures can detect consumption that exceeds levels in the current Australian guidelines (Level B). The Alcohol Use Disorders Identification Test (AUDIT) is the most effective screening tool and is recommended for use in primary care and hospital settings. For screening in the general community, the AUDIT-C is a suitable alternative (Level A). Indirect biological markers should be used as an adjunct to screening (Level A), and direct measures of alcohol in breath and/or blood can be useful markers of recent use (Level B). Assessment Assessment should include evaluation of alcohol use and its effects, physical examination, clinical investigations and collateral history taking (Level C). Assessment for alcohol-related physical problems, mental health problems and social support should be undertaken routinely (GPP). Where there are concerns regarding the safety of the patient or others, specialist consultation is recommended (Level C). Assessment should lead to a clear, mutually acceptable treatment plan which specifies interventions to meet the patient’s needs (Level D). Sustained abstinence is the optimal outcome for most patients with alcohol dependence (Level C). Chapter 3: Caring for and managing patients with alcohol problems: interventions, treatments, relapse prevention, aftercare, and long term follow-up Brief interventions Brief motivational interviewing interventions are more effective than no treatment for people who consume alcohol at risky levels (Level A). Their effectiveness compared with standard care or alternative psychosocial interventions varies by treatment setting. They are most effective in primary care settings (Level A). Psychosocial interventions Cognitive behaviour therapy should be a first-line psychosocial intervention for alcohol dependence. Its clinical benefit is enhanced when it is combined with pharmacotherapy for alcohol dependence or an additional psychosocial intervention (eg, motivational interviewing) (Level A). Motivational interviewing is effective in the short term and in patients with less severe alcohol dependence (Level A). Residential rehabilitation may be of benefit to patients who have moderate-to-severe alcohol dependence and require a structured residential treatment setting (Level D). Alcohol withdrawal management Most cases of withdrawal can be managed in an ambulatory setting with appropriate support (Level B). Tapering diazepam regimens (Level A) with daily staged supply from a pharmacy or clinic are recommended (GPP). Pharmacotherapies for alcohol dependence Acamprosate is recommended to help maintain abstinence from alcohol (Level A). Naltrexone is recommended for prevention of relapse to heavy drinking (Level A). Disulfiram is only recommended in close supervision settings where patients are motivated for abstinence (Level A). Some evidence for off-label therapies baclofen and topiramate exists, but their side effect profiles are complex and neither should be a first-line medication (Level B). Peer support programs Peer-led support programs such as Alcoholics Anonymous and SMART Recovery are effective at maintaining abstinence or reductions in drinking (Level A). Relapse prevention, aftercare and long-term follow-up Return to problematic drinking is common and aftercare should focus on addressing factors that contribute to relapse (GPP). A harm-minimisation approach should be considered for patients who are unable to reduce their drinking (GPP). Chapter 4: Providing appropriate treatment and care to people with alcohol problems: a summary for key specific populations Gender-specific issues Screen women and men for domestic abuse (Level C). Consider child protection assessments for caregivers with alcohol use disorder (GPP). Explore contraceptive options with women of reproductive age who regularly consume alcohol (Level B). Pregnant and breastfeeding women Advise pregnant and breastfeeding women that there is no safe level of alcohol consumption (Level B). Pregnant women who are alcohol dependent should be admitted to hospital for treatment in an appropriate maternity unit that has an addiction specialist (GPP). Young people Perform a comprehensive HEEADSSS assessment for young people with alcohol problems (Level B). Treatment should focus on tangible benefits of reducing drinking through psychotherapy and engagement of family and peer networks (Level B). Aboriginal and Torres Strait Islander peoples Collaborate with Aboriginal or Torres Strait Islander health workers, organisations and communities, and seek guidance on patient engagement approaches (GPP). Use validated screening tools and consider integrated mainstream and Aboriginal or Torres Strait Islander-specific approaches to care (Level B). Culturally and linguistically diverse groups Use an appropriate method, such as the “teach-back” technique, to assess the need for language and health literacy support (Level C). Engage with culture-specific agencies as this can improve treatment access and success (Level C). Sexually diverse and gender diverse populations Be mindful that sexually diverse and gender diverse populations experience lower levels of satisfaction, connection and treatment completion (Level C). Seek to incorporate LGBTQ-specific treatment and agencies (Level C). Older people All new patients aged over 50 years should be screened for harmful alcohol use (Level D). Consider alcohol as a possible cause for older patients presenting with unexplained physical or psychological symptoms (Level D). Consider shorter acting benzodiazepines for withdrawal management (Level D). Cognitive impairment Cognitive impairment may impair engagement with treatment (Level A). Perform cognitive screening for patients who have alcohol problems and refer them for neuropsychological assessment if significant impairment is suspected (Level A). Summary of key recommendations and levels of evidence Chapter 5: Understanding and managing comorbidities for people with alcohol problems: polydrug use and dependence, co-occurring mental disorders, and physical comorbidities Polydrug use and dependence Active alcohol use disorder, including dependence, significantly increases the risk of overdose associated with the administration of opioid drugs. Specialist advice is recommended before treatment of people dependent on both alcohol and opioid drugs (GPP). Older patients requiring management of alcohol withdrawal should have their use of pharmaceutical medications reviewed, given the prevalence of polypharmacy in this age group (GPP). Smoking cessation can be undertaken in patients with alcohol dependence and/or polydrug use problems; some evidence suggests varenicline may help support reduction of both tobacco and alcohol consumption (Level C). Co-occurring mental disorders More intensive interventions are needed for people with comorbid conditions, as this population tends to have more severe problems and carries a worse prognosis than those with single pathology (GPP). The Kessler Psychological Distress Scale (K10 or K6) is recommended for screening for comorbid mental disorders in people presenting for alcohol use disorders (Level A). People with alcohol use disorder and comorbid mental disorders should be offered treatment for both disorders; care should be taken to coordinate intervention (Level C). Physical comorbidities Patients should be advised that alcohol use has no beneficial health effects. There is no clear risk-free threshold for alcohol intake. The safe dose for alcohol intake is dependent on many factors such as underlying liver disease, comorbidities, age and sex (Level A). In patients with alcohol use disorder, early recognition of the risk for liver cirrhosis is critical. Patients with cirrhosis should abstain from alcohol and should be offered referral to a hepatologist for liver disease management and to an addiction physician for management of alcohol use disorder (Level A). Alcohol abstinence reduces the risk of cancer and improves outcomes after a diagnosis of cancer (Level A)

Does time taken by paediatric critical care transport teams to reach the bedside of critically ill children affect survival? A retrospective cohort study from England and Wales

Abstract: Background: Reaching the bedside of a critically ill child within three hours of agreeing the child requires intensive care is a key target for Paediatric Critical Care Transport teams (PCCTs) to achieve in the United Kingdom. Whilst timely access to specialist care is necessary for these children, it is unknown to what extent time taken for the PCCT to arrive at the bedside affects clinical outcome. Methods: Data from transports of critically ill children who were admitted to Paediatric Intensive Care Units (PICUs) in England and Wales from 1 January 2014 to 31 December 2016 were extracted from the Paediatric Intensive Care Audit Network (PICANet) and linked with adult critical care data and Office for National Statistics mortality data. Logistic regression models, adjusted for pre-specified confounders, were fitted to investigate the impact of time-to-bedside on mortality within 30 days of admission and other key time points. Negative binomial models were used to investigate the impact of time-to-bedside on PICU length of stay and duration of invasive ventilation. Results: There were 9116 children transported during the study period, and 645 (7.1%) died within 30 days of PICU admission. There was no evidence that 30-day mortality changed as time-to-bedside increased. A similar relationship was seen for mortality at other pre-selected time points. In children who waited longer for a team to arrive, there was limited evidence of a small increase in PICU length of stay (expected number of days increased from: 7.17 to 7.58). Conclusion: There is no evidence that reducing the time-to-bedside target for PCCTs will improve the survival of critically ill children. A shorter time to bedside may be associated with a small reduction in PICU length of stay

Large-scale diversity and biogeography of benthic copepods in European waters

A large-scale database concerning benthic copepods from the Arctic, Baltic Sea, North Sea, British Isles, Adriatic Sea and Crete was compiled to assess species richness, biodiversity, communities, ecological rangesize and biogeographical patterns. The Adriatic showed the highest evenness and the most species-rich communities. Assemblages from the North Sea, British Isles, Baltic and Crete had a lower evenness. The British Isles were characterised by impoverished communities. The ecological specificity of copepod species showed two diverging trends: higher specificity of species in more diverse assemblages was observed in the Adriatic, North Sea and Baltic. A uniformly high species specificity disregarding sample diversity was found on Crete and in the British Isles. Benthic copepod communities showed distinct patterns that clearly fit the predefined geographical regions. Communities were distinguishable and b-diversity was found to be high around Europe, indicating a high species turnover on the scale of this investigation. The British Isles and the North Sea were found to be faunistic links to the Baltic and the Arctic

Impact of cognitive and physical impairment on carer burden and quality of life

Background and purpose How the cognitive and/or physical impairment experienced by care recipients impacts on their carers is not well understood. This study investigated the effect of type of impairment of care recipients on the level of burden and quality of life (QOL) of elderly Australian carers

Fotossensibilidade e termoestabilidade de vacinas contra o sarampo (cepa Biken CAM-70) liofilizadas e/ou reconstituídas para administração Photosensitivity and stability of freeze-dried and reconstituted (Biken CAM-70) strain measles vaccines

Três lotes de vacinas contra o sarampo, produzidos com a cepa de vírus Biken CAM-70, sob as formas liofilizada e reconstituída, pertencentes ao estoque da rede de vacinação da Secretaria de Estado da Saúde de São Paulo, Brasil, foram submetidos a testes de sensibilidade à luz, à temperatura de 2 a 8&deg;C, e de termoestabilidade (protegidos da luz) às temperaturas de 28, 36,5 e 45&deg;C, objetivando verificar por quanto tempo retinham sua potência, isto é, a concentração ideal recomendada para a cepa de vírus presente (3,70 log 10 DICT50 ou 5.000 doses infectantes de cultura de tecidos 50% por dose). A análise de retas de regressão ajustadas demonstrou que, de modo geral, tanto os lotes de vacinas liofilizados como os reconstituídos, mantidos às referidas temperaturas, expostos ou protegidos da luz, apresentaram queda de potência no decorrer do experimento, a qual foi mais acentuada para vacinas expostas à luz. Reconstituídos e mantidos a 2 a 8&deg;C, os lotes não apresentaram homogeneidade no referente à sensibilidade à luz. Quando a fotossensibilidade de lotes de vacinas liofilizadas foi testada a 2 a 8&deg;C eles mostraram-se mais sensíveis à degradação térmica quando expostos à luz do que quando protegidos dela. Entretanto, expostos ou protegidos, a potência foi inferior à minima aceita para a cepa Biken CAM-70. Às demais temperaturas, mesmo ao abrigo da luz, os dois lotes não retiveram potência mínima. Quanto às vacinas do lote 3, conservadas a 2 a 8&deg;C, mantiveram-se de acordo com os requerimentos mínimos de potência durante 60 dias quando protegidas da luz, e durante 40 dias quando expostas a ela. A degradação térmica às demais temperaturas foi mais acentuada (28&deg;C: 5 dias; 36,5&deg;C: 2 dias; 45&deg;C: 0,5 dia). Considerando a concentração viral mínima que vacinas produzidas com a cepa Biken CAM-70 devem conter para induzir efetiva resposta imunológica, os lotes de vacinas pesquisados (sob a forma liofilizada ou reconstituídos para administração) apresentaram, além de baixa estabilidade ao calor, pouca homogeneidade com relação a este parâmetro.<br>Three different lots of measles vaccines produced with the Biken CAM-70 virus strain were requested from the central cold store of the Public Health Department of the State of S. Paulo, Brazil, and assays on photosensitivity at 2-8&deg; C, and on stability at 28, 36.5 and 45&deg; C were carried out to find out for how long these vaccines would maintain their minimum potency, established as being 3.70 log10 or 5000 TCID50 (50% tissue culture infective dose ) per human dose. The analysis of the adjusted straight regression lines indicated that, with the passage of time, the potency of lyophilized or reconstituted vaccines, as well as of vaccines exposed to or protected from light decreased. Light-exposed vaccines, however, became less potent than vaccines protected from the light. None of the vaccine lots studied, reconstituted and stored at 2-8&deg; C, exhibited homogeneity as to sensitivity to light. When freeze-dried vaccines had their photosensitivity studied at 2-8&deg; C, lots 1 and 2 presented greater thermal degradation when exposed to light than when protected from it. However, in both instances, it was found that potency fell bellow that taken as minimum for the Biken CAM-70 virus strain. At all other temperatures considered, even when protected from light, lots 1 and 2 did not retain the minimum potency. Lot 3 kept the expected stability for 60 days at 2-8&deg; C when protected from light and for 40 days when unprotected, but its thermal degradation at other temperatures was more intense (28&deg; C: 5 days; 36.5&deg; C: 2 days; 45&deg; C: 0.5 day). Taking into account the potency that measles vaccines produced with the Biken CAM-70 virus strain are required to contain in order to induce effective immunity, the three vaccine lots studied were found to possess low thermal stability and to lack homogeneity both in the freeze-dried as well as in the reconstituted form