Impact of socio-economic conditions and perinatal factors on risk of becoming a child looked after: a whole population cohort study using routinely collected data in Wales.

OBJECTIVES: Between 1997 and 2021, the number of children looked after (CLA) in Wales, UK, increased steadily, with stark inequalities. We aimed to assess how deprivation and maternal and child perinatal characteristics influence the risk of becoming CLA in Wales. STUDY DESIGN: We constructed a prospective longitudinal cohort of children born in Wales between April 2006 and March 2021 (n = 395,610) using linked administrative records. METHODS: Survival models examined the risk of CLA from birth by small-area deprivation and maternal and child perinatal characteristics. Population attributable fractions quantify the potential impact of action on modifiable risk factors. RESULTS: Children from the most deprived fifth of the population were 3.4 times more likely to enter care than those in the least deprived (demographic adjusted hazard ratios [aHRs] 3.40, 95% confidence interval [CI] 3.08, 3.74). Maternal mental health problems in pregnancy (fully aHR, 2.03, 95% CI 1.88, 2.19) and behavioural factors, such as smoking (aHR 2.46, 95% CI 2.34-2.60), alcohol problems (aHR 2.35, 95% CI 1.70-3.23) and substance use in pregnancy (aHR 5.72, 95% CI 5.03-6.51), as well as child congenital anomalies (aHR 1.46, 95% CI 1.16-1.84), low birth weight (aHR 1.28, 95% CI 1.17, 1.39) and preterm birth (aHR 1.16, 95% CI 1.06, 1.26), were associated with higher risk of CLA status. The risk of CLA in the population may be reduced by 35% (95% CI 0.33, 0.38) if children in the two most deprived fifths of the population experienced the conditions of those in the least deprived. CONCLUSIONS: Deprivation and perinatal maternal health are important modifiable risk factors for children becoming CLA. Our analysis provides insight into the mechanisms of intergenerational transfer of disadvantage in a vulnerable section of the child population and identifies targets for public health action.

Did the UK's public health shielding policy protect the clinically extremely vulnerable during the COVID-19 pandemic in Wales? Results of EVITE Immunity, a linked data retrospective study.

INTRODUCTION: The UK shielding policy intended to protect people at the highest risk of harm from COVID-19 infection. We aimed to describe intervention effects in Wales at 1 year. METHODS: Retrospective comparison of linked demographic and clinical data for cohorts comprising people identified for shielding from 23 March to 21 May 2020; and the rest of the population. Health records were extracted with event dates between 23 March 2020 and 22 March 2021 for the comparator cohort and from the date of inclusion until 1 year later for the shielded cohort. RESULTS: The shielded cohort included 117,415 people, with 3,086,385 in the comparator cohort. The largest clinical categories in the shielded cohort were severe respiratory condition (35.5%), immunosuppressive therapy (25.9%) and cancer (18.6%). People in the shielded cohort were more likely to be female, aged ≥50 years, living in relatively deprived areas, care home residents and frail. The proportion of people tested for COVID-19 was higher in the shielded cohort (odds ratio [OR] 1.616; 95% confidence interval [CI] 1.597-1.637), with lower positivity rate incident rate ratios 0.716 (95% CI 0.697-0.736). The known infection rate was higher in the shielded cohort (5.9% vs 5.7%). People in the shielded cohort were more likely to die (OR 3.683; 95% CI: 3.583-3.786), have a critical care admission (OR 3.339; 95% CI: 3.111-3.583), hospital emergency admission (OR 2.883; 95% CI: 2.837-2.930), emergency department attendance (OR 1.893; 95% CI: 1.867-1.919) and common mental disorder (OR 1.762; 95% CI: 1.735-1.789). CONCLUSION: Deaths and healthcare utilisation were higher amongst shielded people than the general population, as would be expected in the sicker population. Differences in testing rates, deprivation and pre-existing health are potential confounders; however, lack of clear impact on infection rates raises questions about the success of shielding and indicates that further research is required to fully evaluate this national policy intervention.

Investigating the association between COVID-19 vaccination and care home outbreak frequency and duration.

OBJECTIVES: At the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent and interrupt outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI). STUDY DESIGN: We undertook an ecological study using routinely available national data. METHODS: We used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes, and as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated the number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure. RESULTS: Care home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1625 COVID-19 outbreaks (95% prediction interval 1553-1694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity. CONCLUSIONS: These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.

Mortality after surgery with SARS-CoV-2 infection in England: a population-wide epidemiological study.

BACKGROUND: The COVID-19 pandemic has heavily impacted elective and emergency surgery around the world. We aimed to confirm the incidence of perioperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated mortality after surgery. METHODS: Analysis of routine electronic health record data from NHS hospitals in England. We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between January 1, 2020 and February 28, 2021. The exposure was SARS-CoV-2 infection defined by International Classification of Diseases (ICD)-10 codes. The primary outcome measure was 90 day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson Comorbidity Index, Index of Multiple Deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We identified 2 666 978 patients undergoing surgery of whom 28 777 (1.1%) had SARS-CoV-2 infection. In total, 26 364 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 6153/28 777 [21.4%] vs no SARS-CoV-2: 20 211/2 638 201 [0.8%]; OR=5.7 [95% CI, 5.5-5.9]; P<0.001). Amongst patients undergoing elective surgery, 2412/1 857 586 (0.1%) had SARS-CoV-2, of whom 172/2412 (7.1%) died, compared with 1414/1 857 586 (0.1%) patients without SARS-CoV-2 (OR=25.8 [95% CI, 21.7-30.9]; P<0.001). Amongst patients undergoing emergency surgery, 22 918/582 292 (3.9%) patients had SARS-CoV-2, of whom 5752/22 918 (25.1%) died, compared with 18 060/559 374 (3.4%) patients without SARS-CoV-2 (OR=5.5 [95% CI, 5.3-5.7]; P<0.001). CONCLUSIONS: The low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed.

Impact of a physician - critical care practitioner pre-hospital service in Wales on trauma survival: a retrospective analysis of linked registry data.

The Emergency Medical Retrieval and Transfer Service for Wales launched in 2015. This service delivers senior pre-hospital doctors and advanced critical care practitioners to the scene of time-critical life- and limb-threatening incidents to provide advanced decision-making and pre-hospital clinical care. The impact of the service on 30-day mortality was evaluated retrospectively using a data linkage system. The study included patients who sustained moderate-to-severe blunt traumatic injuries (injury severity score ≥ 9) between 27 April 2015 and 30 November 2018. The association between pre-hospital management by the Emergency Medical Retrieval and Transfer Service and 30-day mortality was assessed using multivariable logistic regression. In total, data from 4035 patients were analysed, of which 412 (10%) were treated by the Emergency Medical Retrieval and Transfer Service. A greater proportion of patients treated by the Emergency Medical Retrieval and Transfer Service had an injury severity score ≥ 16 and Glasgow coma scale ≤ 12 (288 (70%) vs. 1435 (40%) and 126 (31%) vs. 325 (9%), respectively). The unadjusted 30-day mortality rate was 11.7% for patients managed by the Emergency Medical Retrieval and Transfer Service compared with 9.6% for patients managed by standard pre-hospital care services. However, after adjustment for differences in case-mix, the 30-day mortality rate for patients treated by the Emergency Medical Retrieval and Transfer Service was 37% lower (adjusted odds ratio 0.63 (95%CI 0.41-0.97); p = 0.037). The introduction of an emergency medical retrieval service was associated with a reduction in 30-day mortality for patients with blunt traumatic injury.

Long-term trends in critical care admissions in Wales*.

As national populations age, demands on critical care services are expected to increase. In many healthcare settings, longitudinal trends indicate rising numbers and proportions of patients admitted to ICU who are older; elsewhere, including some parts of the UK, a decrease has raised concerns with regard to rationing according to age. Our aim was to investigate admission trends in Wales, where critical care capacity has not risen in the last decade. We used the Secure Anonymised Information Linkage Databank to identify and characterise critical care admissions in patients aged ≥ 18 years from 1 January 2008 to 31 December 2017. We categorised 85,629 ICU admissions as youngest (18-64 years), older (65-79 years) and oldest (≥ 80 years). The oldest group accounted for 15% of admissions, the older age group 39% and the youngest group 46%. Relative to the national population, the incidence of admission rates per 10,000 population in the oldest group decreased significantly over the study period from 91.5/10,000 in 2008 to 77.5/10,000 (a relative decrease of 15%), and among the older group from 89.2/10,000 in 2008 to 75.3/10,000 in 2017 (a relative decrease of 16%). We observed significant decreases in admissions with high comorbidity (modified Charlson comorbidity index); increases in the proportion of older patients admitted who were considered 'fit' rather than frail (electronic frailty index); and decreases in admissions with a medical diagnosis. In contrast to other healthcare settings, capacity constraints and surgical imperatives appear to have contributed to a relative exclusion of older patients presenting with acute medical illness.

The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study.

BACKGROUND: Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce. OBJECTIVES: To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival. METHODS: We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome. RESULTS: During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90). CONCLUSIONS: Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.

HLA-DRB1*15:03 and HLA-DRB1*11: useful predictive alleles for alloantibody production in thalassemia patients.

BACKGROUND AND OBJECTIVES: Recently, thalassemia has been introduced as a chronic disease. In spite of prolonging life in thalassemia patients, the quality of their life has not significantly improved. One of the challenges that makes their quality of life poor is alloimmunisation which causes several complications to patients by restricting their options. Some individuals are more susceptible to developing an alloantibody than others. They are categorised as responders and non-responders. Determining responders before the first transfusion allows transfusion services to provide compatible blood and prevent alloimmunisation. The aim of the present study was to determine the relationship between HLA-DRB1*15:03, HLA-DRB1*11 and HLA-DRB1*09:01 alleles and alloimmunisation in Iranian thalassemia patients. MATERIALS AND METHODS: Antibody screening tests were performed by tube method, and HLA-DRB1 genotyping was determined by Sequence-Specific Primers (SSP-PCR) in 59 alloimmunised and 205 non-alloimmunised patients. HLA-DRB1 allele frequencies were compared between alloantibody-positive and -negative groups through the χ2 test. RESULTS: HLA-DRB1*15:03 allele frequency was significantly different between groups (P = 0·000, odds ratio (OR) = 4·193). There was a correlation between HLA-DRB1*11 and anti-K (P = 0·000, OR = 6·643). There was no association between HLA-DRB1*09:01 and alloimmunisation (P = 0·350). CONCLUSIONS: According to our results, detecting HLA-DRB1*15:03 and HLA-DRB1*11 alleles are useful in the pre-transfusion test and could determine responder patients and improve transfusion safety.

Weekend admission and mortality for gastrointestinal disorders across England and Wales.

BACKGROUND: Little has been reported on mortality following admissions at weekends for many gastrointestinal (GI) disorders. The aim was to establish whether GI disorders are susceptible to increased mortality following unscheduled admission on weekends compared with weekdays. METHODS: Record linkage was undertaken of national administrative inpatient and mortality data for people in England and Wales who were hospitalized as an emergency for one of 19 major GI disorders. RESULTS: The study included 2 254 701 people in England and 155 464 in Wales. For 11 general surgical and medical GI disorders there were little, or no, significant weekend effects on mortality at 30 days in either country. There were large consistent weekend effects in both countries for severe liver disease (England: 26·2 (95 per cent c.i. 21·1 to 31·6) per cent; Wales: 32·0 (12·4 to 55·1 per cent) and GI cancer (England: 21·8 (19·1 to 24·5) per cent; Wales: 25·0 (15·0 to 35·9) per cent), which were lower in patients managed by surgeons. Admission rates were lower at weekends than on weekdays, most strongly for severe liver disease (by 43·3 per cent in England and 51·4 per cent in Wales) and GI cancer (by 44·6 and 52·8 per cent respectively). Both mortality and the weekend mortality effect for GI cancer were lower for patients managed by surgeons. DISCUSSION: There is little, or no, evidence of a weekend mortality effect for most major general surgical or medical GI disorders, but large weekend effects for GI cancer and severe liver disease. Lower admission rates at weekends indicate more severe cases. The findings for severe liver disease may suggest a lack of specialist hepatological resources. For cancers, reduced availability of end-of-life care in the community at weekends may be the cause.

Photochemical synthesis of benzo[f]chromene.

The one-pot photocatalytic synthesis of benzo[f]chromene was performed at room temperature by the addition of benzyl alcohol, malononitrile and ß-naphthol in contact with an illuminated nano-SnO2/TiO2 composite. This study illustrated the potential of photochemical synthesis of benzo[f]chromene. A simple procedure was proposed for the synthesis of a nano-SnO2/TiO2 composite using the sol-gel method by hydrolysis of tin(iv) chloride and titanium(iv) chloride at room temperature in the presence of polyethylene glycol 200, diethanolamine, and distilled water. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and FT-IR were employed to characterize the proposed photocatalyst.

The impact of social deprivation on mortality following hip fracture in England and Wales: a record linkage study.

UNLABELLED: We used routine hospital data to investigate whether socially deprived patients had an increased risk of dying following hip fracture compared with affluent patients. We found that the most deprived patients had a significantly increased risk of dying at 30, 90 and 365 days compared with the most affluent patients. INTRODUCTION: To identify whether social deprivation has any effect on mortality risk after emergency admission with hip fracture and to determine whether any increased mortality observed among deprived groups was associated with patient and hospital-related factors. METHODS: We used routine, linked hospital inpatient and mortality data for emergency admissions with a hip fracture in both England and Wales between 2004 and 2011. Mortality rates at 30, 90 and 365 days were reported. Logistic regression was used to identify any significant increases in mortality with higher levels of social deprivation and the influence of other risk factors on any increased mortality among the most deprived group. RESULTS: Mortality rates at 30, 90 and 365 days were 9.3, 17.4 and 29.0 % in England and 8.3, 16.1 and 27.9 % in Wales. Social deprivation was significantly associated with increased mortality in the most deprived quintile compared with the least deprived quintile at 30, 90 and 365 days in England (OR = 1.187, 1.185 and 1.154, respectively) and at 90 and 365 days in Wales (1.135 and 1.203). There was a little interaction between deprivation and other risk factors influencing 30- and 365-day mortality except for patient age, pre-fracture residence and hospital size. CONCLUSIONS: We demonstrated a positive association between social deprivation and increased mortality at 30 days post-admission for hip fracture in both England and Wales that was still evident at 90 and 365 days. We found little influence of other factors on social inequalities in mortality risk at 30 and 365 days post-admission.

Effects of subcutaneous calcium administration at calving on mineral status, health, and production of Holstein cows.

The objective of this study was to determine effects of subcutaneous (s.c.) infusions of Ca at calving day on serum concentrations of Ca, P, Mg, ß-hydroxybutyrate (BHB), glucose, body condition score (BCS), milk yield, and health in fresh cows receiving a dietary cation-anion difference diet during the dry period. Three hundred seventy-five fresh Holstein cows were blocked based on parity (143 cows in first parity, 108 cows in second parity, and 124 cows in third or greater parity) and randomly assigned to 1 of 4 experimental treatments immediately after calving. Treatments were control group without infusion (control; n=190); 1 s.c. infusion of 250mL of 40% Ca borogluconate (1SC250; n=72) at calving; 1 s.c. infusion of 500mL of 40% Ca borogluconate (1SC500; n=63) at calving; 2 s.c. infusions of 250mL of 40% Ca borogluconate, one immediately after calving and the second 12 to 18h after first infusion (2SC250; n=50). Blood samples were collected immediately after parturition and at 1, 2, 4, and 7d in milk (DIM) for Ca, P, and Mg determination. Milk production, milk composition, and somatic cell count were recorded monthly up to 90 DIM. The evaluation of BCS was performed at calving and at 38 DIM. A subset of 9 cows per treatment group was randomly chosen to measure serum concentration of glucose and BHB at 2, 4, and 7 DIM. Total serum Ca in 1SC250 (8.95mg/dL), 1SC500 (9.27mg/dL), and 2SC250 (9.07mg/dL) was greater during the first week postpartum compared with control (8.45mg/dL). Serum concentrations of P, Mg, BHB, glucose, and milk yield were not affected by treatments. The dry matter intake during the first 24h after calving was higher for treatments 1SC250 (13.5kg), 1SC500 (15.0kg), and 2SC250 (15.6kg) relative to control (12.5kg). Milk somatic cell counts were lower for 1SC500 (90.5 cells/mL) and 2SC250 (82.2 cells/mL) than control (132.8 cells/mL). Risk ratio was >1 for development of metritis, and clinical and subclinical endometritis in control cows relative to 2SC250 cows, which indicates a higher risk of developing disease for control cows (2.03, 1.7, and 1.8 times, respectively). These results suggest that prophylactic s.c. infusions of Ca at calving can improve postpartum Ca status in Holstein cows and intake at 1 DIM. Given the reduction of metritis, clinical and subclinical endometritis, and subclinical hypocalcemia with treatment, the effect of s.c. Ca supplementation on immune status warrants further investigation.

Primary repair with no flaps for lower lip defects (30-80 %) after cancer excision.

Reconstruction of the lip is a necessary procedure when lip tumors are excised. Although many good techniques have been described, they often have disadvantages such as necrosis and extensive suture lines. In our approach, we aim to minimize the suture line and avoid tissue necrosis for medium-sized lip defects (30-80 %). This is a surgical technique report from a single center. After tumor resection, we made a bilateral 15 mm horizontal skin and mucosa incision from the angles of the lip to the lateral sides. The mucosa and skin were dissected from the underlying muscle, and the muscle was cut approximately 15 mm on each side. The lip defect was then closed and sutured in four layers. Finally, the released mucosa was sutured to the corner of the incised skin. We followed the patients for 36 months and found that their speech intelligibility, sensation, mobility, and aesthetic satisfaction were preserved. The scars were also less pronounced compared to flaps, and there were no signs of edema or drooling. In conclusion, our technique offers many advantages for moderate defects of lower lip tumors. By avoiding the use of flaps, we eliminate the complications associated with flap surgery while achieving aesthetically satisfactory results. However, further evaluation by other surgeons is necessary to fully examine the technique's benefits.

Kidney function endpoints in kidney transplant trials: a struggle for power.

Kidney function endpoints are commonly used in randomized controlled trials (RCTs) in kidney transplantation (KTx). We conducted this study to estimate the proportion of ongoing RCTs with kidney function endpoints in KTx where the proposed sample size is large enough to detect meaningful differences in glomerular filtration rate (GFR) with adequate statistical power. RCTs were retrieved using the key word "kidney transplantation" from the National Institute of Health online clinical trial registry. Included trials had at least one measure of kidney function tracked for at least 1 month after transplant. We determined the proportion of two-arm parallel trials that had sufficient sample sizes to detect a minimum 5, 7.5 and 10 mL/min difference in GFR between arms. Fifty RCTs met inclusion criteria. Only 7% of the trials were above a sample size of 562, the number needed to detect a minimum 5 mL/min difference between the groups should one exist (assumptions: α = 0.05; power = 80%, 10% loss to follow-up, common standard deviation of 20 mL/min). The result increased modestly to 36% of trials when a minimum 10 mL/min difference was considered. Only a minority of ongoing trials have adequate statistical power to detect between-group differences in kidney function using conventional sample size estimating parameters. For this reason, some potentially effective interventions which ultimately could benefit patients may be abandoned from future assessment.

COVID-19 vaccination uptake in people with epilepsy in wales.

PURPOSE: People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort. METHODS: We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations. RESULTS: There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability. CONCLUSIONS: COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.

Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

Intravital microscopic observation of the microvasculature during hemodialysis in healthy rats.

Hemodialysis (HD) provides life-saving treatment for kidney failure. Patient mortality is extremely high, with cardiovascular disease (CVD) being the leading cause of death. This results from both a high underlying burden of cardiovascular disease, as well as additional physiological stress from the HD procedure itself. Clinical observations indicate that HD is associated with microvascular dysfunction (MD), underlining the need for a fundamental pathophysiological assessment of the microcirculatory consequences of HD. We therefore successfully developed an experimental small animal model, that allows for a simultaneous real-time assessment of the microvasculature. Using in-house built ultra-low surface area dialyzers and miniaturized extracorporeal circuit, we successfully dialyzed male Wistar Kyoto rats and combined this with a simultaneous intravital microscopic observation of the EDL microvasculature. Our results show that even in healthy animals, a euvolemic HD procedure can induce a significant systemic hemodynamic disturbance and induce disruption of microvascular perfusion (as evidence by a reduction in the proportion of the observed microcirculation receiving blood flow). This study, using a new small animal hemodialysis model, has allowed direct demonstration that microvascular blood flow in tissue in skeletal muscle is acutely reduced during HD, potentially in concert with other microvascular beds. It shows that preclinical small animal models can be used to further investigate HD-induced ischemic organ injury and allow rapid throughput of putative interventions directed at reducing HD-induced multi-organ ischemic injury.

Healthcare contacts with self-harm during COVID-19: An e-cohort whole-population-based study using individual-level linked routine electronic health records in Wales, UK, 2016-March 2021.

INTRODUCTION: Reduced rates of help seeking by those who self-harmed during the COVID-19 pandemic have been reported. OBJECTIVES: To understand changes in healthcare service contacts for self-harm during the COVID-19 pandemic across primary, emergency and secondary care. METHODS: This retrospective cohort study used routine electronic healthcare data for Wales, United Kingdom, from 2016 to March 14, 2021. Population-based data from primary care, emergency departments and hospital admissions were linked at individual-level. All Welsh residents aged ≥10 years over the study period were included in the study. Primary, emergency and secondary care contacts with self-harm at any time between 2016 and March 14, 2021 were identified. Outcomes were counts, incidence, prevalence and proportion of self-harm contacts relative to all contacts in each and all settings, as well as the proportion of people contacting one or more settings with self-harm. Weekly trends were modelled using generalised estimated equations, with differences between 2020 (to March 2021) and comparison years 2016-2018 (to March 2017-2019) quantified using difference in differences, from which mean rate of odds ratios (µROR) across years was reported. RESULTS: The study included 3,552,210 individuals over the study period. Self-harm contacts reduced across services in March and December 2020 compared to previous years. Primary care contacts with self-harm reduced disproportionately compared to non-self-harm contacts (µROR = 0.7, p<0.05), while their proportion increased in emergency departments during April 2020 (µROR = 1.3, p<0.05 in 2/3 comparison years) and hospital admissions during April-May 2020 (µROR = 1.2, p<0.05 in 2/3 comparison years). Despite this, those who self-harmed in April 2020 were more likely to be seen in primary care than other settings compared to previous years (µROR = 1.2, p<0.05). A lower proportion of those with self-harm contacts in emergency departments were subsequently admitted to hospital in December 2020 compared to previous years (µROR = 0.5, p<0.05). CONCLUSIONS: These findings suggest that those who self-harmed during the COVID-19 pandemic may have been less likely to seek help, and those who did so faced more stringent criteria for admission. Communications encouraging those who self-harm to seek help during pandemics may be beneficial. However, this needs to be supported by maintained provision of mental health services.

Effect of solution chemistry and operating conditions on the nanofiltration of acid dyes by a nanocomposite membrane.

A composite nanofiltration membrane was developed by a poly(acrylic acid) in situ ultraviolet (UV) graft polymerization process using an ultrafiltration polysulfone membrane as a porous support, by a phase inversion method. SEM images showed that the PSf membranes had numerous finger-like pores. Atomic force microscopy (AFM) showed that the roughness of the surface was reduced by an increase in UV irradiation times. The rejections of sodium chloride and sodium sulfate were moderate and declined with the increase of concentration. We observed that by increasing UV irradiation time and nanofiltration pressure applied, retention of dyes was enhanced and in the most irradiated membrane (M-4 membrane) at 4 bars, color removal with a high rejection of about 99.80% was achieved. It was found that the separation efficiency of dyes in the mixture of salt and dyes decreased with the salt concentration due to a decrease in the Donnan effect. It was also found that by varying the pH, the membrane surface and the dyes' charges are changed, which meant that the membrane surface and dyes had different interactions at various pHs.