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Prostaglandin E2 (PGE 2 ) and 16,16-dimethyl-PGE 2 (dmPGE 2 ) are important regulators of hematopoietic stem and progenitor cell (HSPC) fate and offer potential to enhance stem cell therapies [C. Cutler et al. Blood 122 , 3074–3081(2013); W. Goessling et al. Cell Stem Cell 8 , 445–458 (2011); W. Goessling et al. Cell 136 , 1136–1147 (2009)]. Here, we report that PGE 2 -induced changes in chromatin at enhancer regions through histone-variant H2A.Z permit acute inflammatory gene induction to promote HSPC fate. We found that dmPGE 2 -inducible enhancers retain MNase-accessible, H2A.Z-variant nucleosomes permissive of CREB transcription factor (TF) binding. CREB binding to enhancer nucleosomes following dmPGE 2 stimulation is concomitant with deposition of histone acetyltransferases p300 and Tip60 on chromatin. Subsequent H2A.Z acetylation improves chromatin accessibility at stimuli-responsive enhancers. Our findings support a model where histone-variant nucleosomes retained within inducible enhancers facilitate TF binding. Histone-variant acetylation by TF-associated nucleosome remodelers creates the accessible nucleosome landscape required for immediate enhancer activation and gene induction. Our work provides a mechanism through which inflammatory mediators, such as dmPGE 2 , lead to acute transcriptional changes and modify HSPC behavior to improve stem cell transplantation.

Prostaglandin E2 (PGE2) and 16,16-dimethyl-PGE2 (dmPGE2) are important regulators of hematopoietic stem and progenitor cell (HSPC) fate and offer potential to enhance stem cell therapies1,2. The mechanism of gene regulation in response to dmPGE2 is poorly understood. Here, we show that dmPGE2 regulates inflammatory gene induction by modulating the chromatin architecture and activity of enhancer elements in human HSPCs. We identified the specific genomic reorganization at stimuli-responsive enhancers that permits rapid transcriptional activation. We found that dmPGE2-inducible enhancers retain MNase-accessible, H2A.Z-variant nucleosomes that are permissive to binding of the transcription factor CREB. CREB binding to enhancer nucleosomes is concomitant with deposition of the histone acetyltransferases p300 and Tip60 on chromatin. Subsequent H2A.Z acetylation improves chromatin accessibility at stimuli-responsive enhancers. Our findings support a model where histone variant nucleosomes retained within inducible enhancers facilitate transcription factor (TF) binding. Acetylation of histone variant nucleosomes by TF-associated nucleosome remodelers creates the accessible nucleosome landscape required for immediate enhancer activation and gene induction. Our work provides a mechanism by which inflammatory mediators such as dmPGE2 lead to acute transcriptional changes and alter HSPC behavior.

Eccrine porocarcinoma (EPC) is a rare sweat gland malignancy. Recognition of histologic features is challenging, and specific pathologic features correlate with risk of poor outcome. This single-center retrospective review and case series of 58 EPC cases from 2000 to 2016 elucidates epidemiologic and pathologic characteristics of EPC. Pathology slides from 52 cases were analyzed by a dermatopathologist for standardized variable characteristics, including previously determined high-risk features (HRF) associated with poor prognosis. The incidence of EPC increased over the study period with 3 times more cases diagnosed in the last 4 years than in the first 4 years. Most cases were in the elderly males (mean age 75 years), and 50% were located in the head and neck region. Although 38% of tumors exhibited one histologic HRF, only 10% exhibited more than one. Of the HRF, a greater tumor depth was associated with both increased age (P = 0.04) and clear cell differentiation (P = 0.02). This study elucidates epidemiologic and pathologic features of EPC and highlights how age and clear cell differentiation can be associated with greater tumor depth, although further research is needed to determine whether clear cell differentiation is associated with poor clinical outcome.

Background Immune checkpoint inhibitor (ICI) is an essential part of the treatment of various advanced cancers, but its use can be associated with a number of side effects, including hypercalcemia. The mechanism through which hypercalcemia arises is not well established. One proposed mechanism is through sarcoidosis-like reactions. Here we present an illustrative case. Clinical Case A 75-year-old female with past medical history notable for stage IV endometrial adenocarcinoma treated with surgery plus adjuvant chemotherapy, presently on pembrolizumab for 9 months, hypertension, and diabetes was admitted with generalized fatigue, difficulty ambulating, slow movements, and slow speech. Stroke was ruled out with negative neurologic imaging. Blood work revealed elevated calcium 13.8 mg/dL (8.6-10.4 mg/dL) and ionized calcium 1.64 mmol/L (1.09-1.29 mmol/L). Additional workup showed suppressed PTH 7 pg/mL (11-51 pg/mL), 25-OH vitamin D 19 ng/mL (20-50 ng/mL), elevated 1,25(OH)2 vitamin D of 114 pg/mL (19.9-79.3 pg/mL), elevated angiotensin converting enzyme (ACE) level 90 U/L (12-69 U/L), and normal PTHrP, suggestive of PTH-independent hypercalcemia mediated by 1,25(OH)2D as seen in sarcoidosis. Two months prior to admission and seven months after starting pembrolizumab, surveillance CT found improvement in tumor burden but new intrathoracic lymphadenopathy. Lymph node biopsy via bronchoscopy identified non-caseating granulomas suggestive of a sarcoidosis-like reaction. The patient's moderate hypercalcemia was treated with intravenous fluids, calcitonin, and zoledronic acid 4 mg with normalization of calcium levels. Glucocorticoid therapy was initially deferred to avoid counteracting the effect of pembrolizumab, however prednisone 10 mg daily was started 1 month after discharge when calcium rose again to 11.1 mg/dL. Prednisone was tapered off over 8 weeks as her calcium and 1,25(OH)2D levels normalized. She then restarted pembrolizumb, but after the third month she had recurrence of hypercalcemia (calcium 10.8 mg/dL) with elevated 1,25(OH)2D (89.5 pg/mL). She was again treated with prednisone 10 mg daily which was tapered off over 6 weeks with resolution of hypercalcemia. Her calcium levels remained normal off pembrolizumab. The temporal correlation in our case strongly suggests that ICI administration caused sarcoidosis-like granulomas and hypercalcemia. Conclusion Immune checkpoint inhibitors are known to occasionally cause hypercalcemia, although the mechanisms are not well established. In our case, moderate hypercalcemia was likely caused by ICI-induced sarcoid-like granulomas that responded promptly to glucocorticoids and interruption of ICI-therapy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.

There is a paucity of evidence on the role, use, benefit and challenges of artificial nutrition and hydration (ANH) in children at end of life. Parents express the difficulty they face with making the decision to withdraw ANH. Decision-making on the role of ANH in an individual child requires careful multidisciplinary team deliberation and clear goals of care with children and families. Four paediatric palliative care specialist centres reviewed the current literature and developed consensus guidelines on ANH at end of life. These guidelines seek to provide a practical approach to clinical decision-making on the role of ANH in a child or young person entering the end-of-life phase.

Background: Few epidemiologic studies have investigated trace element exposure and skin cancer risk. Methods: Toenail levels of mercury, selenium, chromium, iron, and zinc were measured from 6,708 women in the Nurses' Health Study (1984–2012) and 3,730 men in the Health Professionals Follow-up Study (1986–2012) with data from prior nested case–control studies. Participants were free of skin cancer at toenail collection and followed for incident basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of skin cancer associated with the elements in each study. We calculated pooled multivariable HRs using a fixed-effects model. During 26 to 28 years of follow-up, 2,433 BCC, 334 SCC, and 130 melanoma cases were documented. Results: Higher toenail mercury levels were associated with risk of BCC [pooled HR for top vs. bottom quintiles = 1.34 (95% CI, 1.18–1.52), Ptrend < 0.0001]. Similar direct associations were found with risks of SCC [pooled HR for top vs. bottom quartiles = 1.41 (95% CI, 1.03–1.94), Ptrend = 0.04] and melanoma [pooled HR for top vs. bottom quartiles = 1.88 (95% CI, 1.12–3.16), Ptrend = 0.02]. Chromium was positively associated with BCC in women only. No associations were found between other metals and skin cancer risk. Conclusions: Our prospective data found that increased toenail mercury concentrations were associated with increased skin cancer risk. Impact: If our novel findings are confirmed, mercury may play a role in skin carcinogenesis.

AimUnderstanding of coping strategies that parents use before the death of their child is crucial and will enable us to best provide support. The current study aimed to explore parents’ coping strategies, and map these onto an existing theoretical framework.MethodsBereaved parents and parents of a child with a life‐limiting/threatening condition were interviewed to investigate coping strategies, recruited through Intensive Care Units (2 Neonatal, 2 Paediatric, 1 Paediatric Cardiac) and a children's hospice. Analysis focused on coping strategies and mapping these onto the framework.Results24 parents of 20 children were interviewed and identified. Parents use a variety of coping strategies (n = 25) such as humour, staying positive, advocating and staying strong for others, expressing emotions and preparing, while also living life to the full, supported by others. The themes were successfully mapped onto the theoretical framework, which focuses on the constructs of approach and avoidance, as well as coping for self and others.ConclusionThe findings have provided a detailed account of the breadth and depth of coping strategies parents use, including those classed as avoidance. The strategies were successfully mapped onto the theoretical framework. Future research should investigate changes over times, and associations to negative long‐term outcomes.

Background The uptake and adherence of daily oral PrEP has been poor in high-risk populations in South Africa including young people. We used qualitative research methods to explore user preferences for daily and on-demand oral PrEP use among young South Africans, and to inform the identification of critical attributes and attribute-levels for quantitative analysis of user preferences, i.e. a discrete choice experiment (DCE). Methods Data were collected between September and November 2018 from eight group discussions and 20 in-depth interviews with young people 13 to 24 years in Cape Town and Johannesburg. Using a convenience sampling strategy, participants were stratified by sex and age. Interviewers used a semi-structured interview guide to discuss several attributes (dosing regimen, location, costs, side effects, and protection period) for PrEP access and use. Group discussions and in-depth interviews were audio-recorded, transcribed verbatim and translated to English. We used framework analysis to explore context-specific attributes and attribute-levels for delivering oral PrEP in South Africa. The adolescent community advisory board, expert and study team opinions were consulted for the final DCE attributes and levels. Results We enrolled 74 participants who were 51% (n = 38/74) male, had a median age of 18.5 [Interquartile range = 16–21.25] years, 91% (n = 67/74) identified as heterosexual and 49% (n = 36/74) had not completed 12th grade education. Using the qualitative data, we identified five candidate attributes including (1) dosing regimen, (2) location to get PrEP, (3) cost, (4) route of administration and (5) frequency. After discussions with experts and the study team, we revised the DCE to include the following five attributes and levels: dosing regime: daily, and on-demand PrEP; location: private pharmacy, public clinic, mobile clinic, ATM); cost: free-of-charge, R50 (~2GBP), R265 (~12GBP); side effects: nausea, headache, rash; and duration of protection: fulltime protection versus when PrEP is used). Conclusions There is limited literature on qualitative research methods describing the step-by-step process of developing a DCE for PrEP in adolescents, especially in resource-constrained countries. We provide the process followed for the DCE technique to understand user preferences for daily and on-demand oral PrEP among young people in South Africa.

Evidence is accumulating that the establishment of the gut microbiome in early life influences the development of atopic eczema. In this longitudinal study, we used integrated multi-omics analyses to infer functional mechanisms by which the microbiome modulates atopic eczema risk. We measured the functionality of the gut microbiome and metabolome of 63 infants between ages 3 weeks and 12 months with well-defined eczema cases and controls in a sub-cohort from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort. At 3 weeks, the microbiome and metabolome of allergen-sensitized atopic eczema infants were characterized by an enrichment of Escherichia coli and Klebsiella pneumoniae, associated with increased stool D-glucose concentration and increased gene expression of associated virulence factors. A delayed colonization by beneficial Bacteroides fragilis and subsequent delayed accumulation of butyrate and propionate producers after 3 months was also observed. Here, we describe an aberrant developmental trajectory of the gut microbiome and stool metabolome in allergen sensitized atopic eczema infants. The infographic describes an impaired developmental trajectory of the gut microbiome and metabolome in allergen-sensitized atopic eczema (AE) infants and infer its contribution in modulating allergy risk in the Singaporean mother-offspring GUSTO cohort. The key microbial signature of AE is characterized by (1) an enrichment of Escherichia coli and Klebsiella pneumoniae which are associated with accumulation of pre-glycolysis intermediates (D-glucose) via the trehalose metabolic pathway, increased gene expression of associated virulence factors (invasin, adhesin, flagellin and lipopolysaccharides) by utilizing ATP from oxidative phosphorylation and delayed production of butyrate and propionate, (2) depletion of Bacteroides fragilis which resulted in lower expression of immunostimulatory bacterial cell envelope structure and folate (vitamin B9) biosynthesis pathway, and (3) accompanied depletion of bacterial groups with the ability to derive butyrate and propionate through direct or indirect pathways which collectively resulted in reduced glycolysis, butyrate and propionate biosynthesis., Graphical abstract

Background Oral Pre-Exposure Prophylaxis (PrEP) was approved for use in South Africa (SA) in 2017. The uptake and adherence of daily oral PrEP has been poor in high-risk populations in SA including adults and young people. We used a Discrete Choice Experiment (DCE) technique to identify critical attributes and attribute-levels to understand user preferences for daily and on-demand oral PrEP use among young people, including adolescents, in two South African cities. Methods Qualitative data were collected between September and November 2018 from 8 group discussions and 20 in-depth interviews with young people aged 13 to 24 years in Cape Town and Johannesburg. Participants were selected based on stratified (gender and age) purposive sampling. Using a semi-structured interview guide, interviewers discussed several attributes (dosing regimen, location, costs, side effects, and protection period) for PrEP access and use. Transcripts were coded to identify context-specific attributes and attribute-levels for delivering oral PrEP in South Africa. The adolescent community advisory board, expert and study team opinions were consulted for the final DCE attributes and levels. Results We enrolled 74 participants: 51% (n=38/74) male, median age of 18.5 [IQR=16-21.25] years, 91% (n=67/74) identified as heterosexual and 49% (n=36/74) had not completed 12th grade education. Using the qualitative data, we identified five candidate attributes including (1) dosing regimen, (2) location to get PrEP, (3) cost, (4) route of administration and (5) frequency. After discussions with experts and the study team, we revised the DCE to include the following five attributes and levels: dosing regime: daily, and on-demand PrEP; location: private pharmacy, public clinic, mobile clinic, ATM); cost: free-of-charge, R50 (~2GBP), R265 (~12GBP); side effects: nausea, headache, rash; and duration of protection: fulltime protection versus when PrEP is used). Conclusions There is limited methodological literature describing the step-by-step process of developing a DCE for PrEP in adolescents, especially in resource-constrained countries. We provide the process followed for the DCE technique to understand user preferences for daily and on-demand oral PrEP among young people in South Africa.

Merkel cell carcinoma (MCC) is an uncommon aggressive cutaneous neuroendocrine tumor with high mortality. The purpose of this study is to describe the clinical correlates of MCC and identify changing trends over time using a retrospective chart review of 113 cases in a single tertiary center pathology database from 1997 to 2015. MCC occurred mostly in the elderly (median age 77 years), more often in males (n = 60, 53%), was most commonly located on the head and neck region (n = 63, 56%), and most commonly presented on the left side of the body (n = 59, 52%). Overall, there was an increase in MCC diagnoses per year from 1997 to 2015, with 2.3 times more cases diagnosed in the last 3 years of the study period than in the first 3 years. Furthermore, cases diagnosed after 2008 were more likely to occur in younger patients, less than or equal to 77 years of age (OR 2.32, 95% CI 1.08, 4.97, p = 0.04). The median age of diagnosis among females was 76 years and among males was 74 years. There was no change in the overall age of diagnosis among men and a decrease in age of diagnosis among females during the study. There was an overall increase in the MCC cases diagnosed among women, and a slight increase in the proportion of females affected by MCC throughout the course of the study. This retrospective case series elucidates MCC epidemiologic characteristics and describes how incidence, sex, and age at diagnosis have changed over the course of the study.

Background: While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria is a worldwide public health concern. Better understanding of the naïve infant gut resistome may build the evidence base for antimicrobial stewardship in both humans and in the food industry. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Asia, we aimed to evaluate community prevalence, dynamics, and longitudinal changes in antibiotic resistance gene (ARG) profiles and prevalence of ESBL-producing E. coli and K. pneumoniae in the intestinal microbiome of infants participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a longitudinal cohort study of pregnant women and their infants. Methods: We analysed ARGs in the first year of life among 75 infants at risk of eczema who had stool samples collected at multiple timepoints using metagenomics. Results: The mean number of ARGs per infant increased with age. The most common ARGs identified confer resistance to aminoglycoside, beta-lactam, macrolide and tetracycline antibiotics; all infants harboured these antibiotic resistance genes at some point in the first year of life. Few ARGs persisted throughout the first year of life. Beta-lactam resistant Escherichia coli and Klebsiella pneumoniae were detected in 4 (5.3%) and 32 (42.7%) of subjects respectively. Conclusion: In this longitudinal cohort study of infants living in a region with high endemic antibacterial resistance, we demonstrate that majority of the infants harboured several antibiotic resistance genes in their gut and showed that the infant gut resistome is diverse and dynamic over the first year of life. Agency for Science, Technology and Research (A*STAR) Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version The study was supported by the National Medical Research Council Clinician Scientists Individual Research Grant (R-178-000-222-511) provided by the Ministry of Health (Singapore). This research is also supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore- NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. The funders are not involved in the design and conduct of the study, data analysis and preparation of manuscript.

Objective To facilitate improved and earlier access to palliative care for babies, a 4-h workshop on the principles, practice and resources in palliative care was delivered in 21 neonatal units across London. This paper assesses the impact of these workshops. Design As part of mixed methods, processual evaluation of a series of education workshops, a pre and post survey instrument was developed, consisting of open and closed questions assessing knowledge of services and attitudes towards palliative care. Before and after each workshop attendees were invited to complete the survey. Setting Neonatal units in hospitals across London, including examples of intensive care, high dependency and special care units. Results 331 healthcare professionals attended the sessions, and 264 (80%) completed questionnaires. The majority of attendees were experienced neonatal nurses working in neonatal intensive care (61% more than 7 years) but with limited experience of palliative care services. Over 79% of respondents reported that the workshop completely met their learning needs. Post-session 80% of respondents felt confident referring to palliative care services, compared with 46% before (p

Summary Introduction Although sleep disturbances in disabled children are of central clinical importance, there is little research on that topic. There are no data available on frequency, severity or aetiology of sleep disturbances and related symptoms in this specific patient group. Objective To review the current state of research and outline future research objectives. Methods We searched international scientific databases for relevant publications from 1980-2009. From all papers qualifying for further analysis we retrieved systematic information on sample characteristics, sleep assessment tools and their test quality criteria, and core findings. Results 61 publications including 4392 patients were categorized as "mixed" (reporting on heterogeneous diagnoses), or "specified" papers (specific diagnoses) based on international classification of diseases (ICD) 10 classification. To assess sleep disturbances, most authors relied on subjective instruments with poor psychometric quality. Mean prevalence of sleep disturbances was 67% (76%,"mixed" group; 65%, "specified" group). In children suffering severe global cerebral injury, the prevalence of sleep disturbances was even higher (>90%). The most frequent symptoms were insomnia and sleep-related respiratory disorders. Some of these symptoms were closely associated with specific medical syndromes. Conclusion There is an urgent need for sleep disturbance assessment tools evaluated for the patient group of interest. By use of validated assessment tools, patient factors, which may be crucial in causing sleep disturbances, may be investigated and appropriate treatment strategies may be developed.

Background Children with severe psychomotor impairment (SPMI) often experience sleep disturbances that severely distress both the child and his or her parents. Validated questionnaires for the assessment of parents' distress related to their child's sleep disturbances are lacking. Methods We developed and validated a new questionnaire, the HOST ( ho listic assessment of s leep and daily t roubles in parents of children with SPMI) to assess the effect of the sleep disturbances in children with SPMI on their parents. The questionnaire was developed based on published data and expert opinion, and it was refined via direct consultation with affected parents. Its psychometric characteristics were assessed in a sample of parents of 214 children with SPMI. It was retested using a random subsample of the participants. Results Explorative factor analysis revealed that the HOST was composed of four scales. Fit indices, item analysis, and convergent validity (coherence with preexisting instruments of sleep disturbances and health status) were adequate. Retest analysis ( n =62) revealed high stability of the HOST questionnaire and adequate replication validity. Conclusion Sleep-related difficulties significantly impact the sociomedical characteristics of the parents of children with complex neurologic diseases. Typically, parents are severely affected in various aspects of daily life (i.e., medical health, social life, professional life). The HOST proved to be a valid, reliable and economical assessment tool of sleep-related difficulties in parents and relatives of children with SPMI. The HOST is capable of identifying individuals and specific areas requiring intervention.

A case of a 12-year-old female with complex regional pain syndrome (CRPS) is presented. Difficulties making the diagnosis are described. The importance of using an interdisciplinary approach that includes appropriate pharmacotherapy are discussed.

Objective Sleep disturbance and daytime restlessness are present in 50% to 80% of children with severe psychomotor impairment due to neurologic or other complex diseases. Although these issues severely impair the quality of life of the children and their families, they are not well addressed or managed by professionals. The lack of validated assessment tools prevents further research and the development of adequate therapies. Our aim is to develop and validate a sleep questionnaire for these children that could be used both for clinical management and systematic research. Methods The sleep questionnaire for children with severe psychomotor impairment (Schlaffragebogen fur Kinder mit Neurologischen und Anderen Komplexen Erkrankungen, SNAKE) is based on expert opinion and consultation with parents. The psychometric quality of the questionnaire was assessed in a sample of 224 children with severe psychomotor impairment. Results Confirmative factor analysis showed that SNAKE comprises of five factors (based on ICSD-2). Fit indices, analysis of item characteristics and convergent validity (coherence with measures of sleep [i.e., sleep efficiency]) and correlation with selected subscales of the Sleep Disturbance Scale for Children (SDSC) were good. Re-test analysis ( n =62) depicted high stability and good replication of validity. Conclusions SNAKE is a reliable and valid tool for the diagnosis of sleep disturbances in children with severe psychomotor impairment. The SNAKE questionnaire is the first tool that addresses the specific relationship between sleep disturbance and severe disability in children.

Palliative care is an expanding specialty within paediatrics, which has attracted little attention in the paediatric radiological literature. Paediatric patients under a palliative care team will have numerous radiological tests which we traditionally categorise under organ systems rather than under the umbrella of palliative medicine. The prevalence of children with life-limiting illness is significant. It has been estimated to be one per thousand, and this may be an underestimate. In this review, we will focus on our experience at one institution, where radiology has proven to be an invaluable partner to palliative care. We will discuss examples of conditions commonly referred to our palliative care team and delineate the crucial role of diagnostic radiology in determining treatment options.

The ‘3-R’ approach of Organisational Health Management is Singapore Police Force’s (SPF) response to the need for a conceptual support framework. These three ‘Rs’ are ‘Risk Reduction’, ‘Re-interpretative Response’ and ‘Restoration to Normalcy'. The ‘3-R’ approach has been structured along the lines of the three-pronged prevention framework: that is, ‘Primary’, ‘Secondary’ and ‘Tertiary’ prevention. A common risk-reduction strategy employed by many police organisations to reduce ‘person-to-organisation’ misfit is pre-employment assessment. The SPF has also been using psychological assessments to enhance ‘person-to-job’ fit and make ‘placement’ decisions. An ‘organisation stress-diagnostic’ tool employed regularly by the SPF is the ‘Organisational Health Survey’ (OHS), which has been used on three occasions since 1997 in the SPF. A ‘critical incident’ is ‘any event which has a stressful impact sufficient to overwhelm the usual coping skills of either an individual or a group. Keywords: 3-R approach; organisation stress-diagnostic tool; Organisational Health Survey (OHS); risk-reduction strategy; Singapore Police Force’s (SPF) response

Until recent years, there has been limited therapeutic options for patients with pulmonary hypertension (PAH). Sildenafil, a phosphodiesterase-5 inhibitor has been the latest addition after recent positive results of the randomized control trial by the sildenafil use in Pulmonary Arterial Hypertension group [1]. These patients showed improved exercise capacity, WHO functional class and hemodynamics [2,3]. Sildenafil unfortunately has a short half life of 4 h. Repeated doses required may lead to reduced compliance. Tadalafil, a long acting PDE5 inhibitor with a half life of 18 h [4] may offer similar improvement at reduced cost and improved compliance in PAH patients. We assessed the impact of change from sildenafil to tadalafil on exercise capacity, NYHA functional class and hemodynamics in 12 patients who have had prior response to sildenafil.

Background In an effort to facilitate improved and earlier access to palliative care (PC) for babies and their families, a 4 h educational workshop on the principles, practice and resources in PC was offered in 21 neonatal units across London. Each workshop was tailored to ensure locally relevant information. This paper assesses the impact of these workshops. Aim To evaluate the impact of a short 4 h workshop on the attitudes towards PC and knowledge of services among neonatal clinical staff. Methods Before and after each workshop, attendees completed a survey of open and closed questions to assess changes in attitudes and knowledge. Descriptive statistical analyses were conducted with SPSS, and thematic analysis of open-ended responses with NVIVO software. Results 331 healthcare professionals attended the sessions, and 264 (80%) completed questionnaires. The majority of attendees were experienced neonatal nurses working in NICU, with limited experience making referrals to PC services. Statistical tests showed significant (p Conclusions A short locally delivered workshop can change attitudes and increase knowledge in neonatal staff. Further work is being conducted to assess the impact of such changes on clinical practice, including referral to community and specialist PC services.