"I am in favour of organ donation, but I feel you should opt-in"-qualitative analysis of the #options 2020 survey free-text responses from NHS staff toward opt-out organ donation legislation in England.

BACKGROUND: In May 2020, England moved to an opt-out organ donation system, meaning adults are presumed to be an organ donor unless within an excluded group or have opted-out. This change aims to improve organ donation rates following brain or circulatory death. Healthcare staff in the UK are supportive of organ donation, however, both healthcare staff and the public have raised concerns and ethical issues regarding the change. The #options survey was completed by NHS organisations with the aim of understanding awareness and support of the change. This paper analyses the free-text responses from the survey. METHODS: The #options survey was registered as a National Institute of Health Research (NIHR) portfolio trial [IRAS 275992] 14 February 2020, and was completed between July and December 2020 across NHS organisations in the North-East and North Cumbria, and North Thames. The survey contained 16 questions of which three were free-text, covering reasons against, additional information required and family discussions. The responses to these questions were thematically analysed. RESULTS: The #options survey received 5789 responses from NHS staff with 1404 individuals leaving 1657 free-text responses for analysis. The family discussion question elicited the largest number of responses (66%), followed by those against the legislation (19%), and those requiring more information (15%). Analysis revealed six main themes with 22 sub-themes. CONCLUSIONS: The overall #options survey indicated NHS staff are supportive of the legislative change. Analysis of the free-text responses indicates that the views of the NHS staff who are against the change reflect the reasons, misconceptions, and misunderstandings of the public. Additional concerns included the rationale for the change, informed decision making, easy access to information and information regarding organ donation processes. Educational materials and interventions need to be developed for NHS staff to address the concepts of autonomy and consent, organ donation processes, and promote family conversations. Wider public awareness campaigns should continue to promote the positives and refute the negatives thus reducing misconceptions and misunderstandings. TRIAL REGISTRATION: National Institute of Health Research (NIHR) [IRAS 275992].

NHS staff awareness, attitudes and actions towards the change in organ donation law in England-results of the #options survey 2020.

BACKGROUND: In Spring 2020 there was a change in organ donation legislation in England (UK). Much is known about public opinions to organ donation and the change in legislation, however, there is little evidence about the opinions of the NHS workforce. This study set out to understand the levels of awareness, support and action of NHS staff to this change and explore the impact of respondent demographics, place and type of work on awareness, support and action. METHODS: An online survey was offered to all NHS organisations in North Thames and the North East and North Cumbria through the NIHR Clinical Research Network between July and December 2020. Participating organisations were provided with an information package and promoted the survey via email and internal staff communications. Associations were compared univariately using chi-square tests and logistic regression was used for multivariable analysis to compare findings with NHS Blood and Transplant public Kantar survey data. RESULTS: A total of 5789 staff participated in the survey. They were more aware, more supportive, more likely to have discussed their organ donation choices with family and more likely to be on the organ donor register than the public. This increased awareness and support was found across minority ethnic and religious groups. Those working in a transplanting centre were most aware and supportive and those working in the ambulance service were most likely to 'opt-in' following the change in legislation. CONCLUSIONS: NHS staff in England were well informed about the change in organ donation legislation and levels of support were high. NHS staff were six times more likely than the public to have a conversation with their family about their organ donation choices. The size and ethnic diversity of the NHS workforce offers an opportunity to enable and support NHS staff to be advocates for organ donation and raise awareness of the change in legislation amongst their communities.

NIMO-CKD-UK: a real-world, observational study of iron isomaltoside in patients with iron deficiency anaemia and chronic kidney disease.

BACKGROUND: Intravenous iron is often used to treat iron deficiency anaemia in non-dialysis chronic kidney disease (ND-CKD), but the optimal dosing regimen remains unclear. We evaluated the impact of high- versus low-dose intravenous iron isomaltoside on the probability of retreatment with intravenous iron in iron-deficient ND-CKD patients. METHODS: This real-world, prospective, observational study collected data from 256 ND-CKD patients treated for anaemia in the UK. Following an initial course of iron isomaltoside, patients were followed for ≥12 months. Iron dose and the need for retreatment were determined at the investigators' discretion. The primary study outcome was the need for retreatment at 52 weeks compared between patients who received >1000 mg of iron during Course 1 and those who received ≤1000 mg. Safety was evaluated through adverse drug reactions. RESULTS: The probability of retreatment at Week 52 was significantly lower in the >1000 mg iron group (n = 58) versus the ≤1000 mg group (n = 198); hazard ratio (95% confidence interval [CI]): 0.46 (0.20, 0.91); p = 0.012. Mean (95% CI) haemoglobin increased by 6.58 (4.94, 8.21) g/L in the ≤1000 mg group and by 10.59 (7.52, 13.66) g/L in the >1000 mg group (p = 0.024). Changes in other blood and iron parameters were not significantly different between the two groups. Administering >1000 mg of iron isomaltoside saved 8.6 appointments per 100 patients compared to ≤1000 mg. No serious adverse drug reactions were reported. Of the patients who received ≤1000 mg of iron in this study, 82.3% were eligible for a dose >1000 mg. CONCLUSIONS: The >1000 mg iron isomaltoside regimen reduced the probability of retreatment, achieved a greater haemoglobin response irrespective of erythropoiesis-stimulating agent treatment, and reduced the total number of appointments required, compared to the ≤1000 mg regimen. Many of the patients who received ≤1000 mg of iron were eligible for >1000 mg, indicating that there was considerable underdosing in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02546154 , 10 September 2015.

Identification of compound heterozygous KCNJ1 mutations (encoding ROMK) in a kindred with Bartter's syndrome and a functional analysis of their pathogenicity.

A multiplex family was identified with biochemical and clinical features suggestive of Bartter's syndrome (BS). The eldest sibling presented with developmental delay and rickets at 4 years of age with evidence of hypercalciuria and hypokalemia. The second sibling presented at 1 year of age with urinary tract infections, polyuria, and polydipsia. The third child was born after a premature delivery with a history of polyhydramnios and neonatal hypocalcemia. Following corrective treatment she also developed hypercalciuria and a hypokalemic metabolic alkalosis. There was evidence of secondary hyperreninemia and hyperaldosteronism in all three siblings consistent with BS. Known BS genes were screened and functional assays of ROMK (alias KCNJ1, Kir1.1) were carried out in Xenopus oocytes. We detected compound heterozygous missense changes in KCNJ1, encoding the potassium channel ROMK. The S219R/L220F mutation was segregated from father and mother, respectively. In silico modeling of the missense mutations suggested deleterious changes. Studies in Xenopus oocytes revealed that both S219R and L220F had a deleterious effect on ROMK-mediated potassium currents. Coinjection to mimic the compound heterozygosity produced a synergistic decrease in channel function and revealed a loss of PKA-dependent stabilization of PIP2 binding. In conclusion, in a multiplex family with BS, we identified compound heterozygous mutations in KCNJ1. Functional studies of ROMK confirmed the pathogenicity of these mutations and defined the mechanism of channel dysfunction.

Truly resistant hypertension?

A young man presented with severe hypertension with evidence of both neurological and cardiovascular end-organ damage. Investigation revealed a small right kidney and a left renal artery aneurysm. Significant hypertension persisted even after right nephrectomy. Despite extensive investigation, no evidence was found to implicate the aneurysm in the causation of his high blood pressure. No alternative cause for hypertension was found, yet blood pressure was high even during hospital admission and observed medication dosing with eight antihypertensive agents. Sustained hypertension resulted in worsening left ventricular hypertrophy and he died suddenly at a tragically young age several years after presentation. This gentleman had truly resistant hypertension, a clinical problem which can be very difficult to manage.

Polyarteritis nodosa presenting with frank hematuria.

Polyarteritis nodosa (PAN) is an uncommon systemic vasculitis characterized by necrotizing inflammation of small- or medium-sized arteries. The disease normally presents with non-specific symptoms. Urological symptoms at presentation are extremely rare. We report a 65-year-old man who was diagnosed with a polyarteritis nodosa having presented atypically with left testicular pain and swelling, and an intratesticular lesion. He developed painless visible hematuria while under investigation. No gross arterio-venous fistula was seen to suggest a false aneurysm. Subsequently, laboratory studies showed positive anti-neutrophil cytoplasmic antibody levels and a raised erythrocyte sedimentation rate. This was an unusual presentation of PAN diagnosed with multidisciplinary input from the urology, radiology and nephrology teams.

Effects of feeding on albumin synthesis in hypoalbuminemic hemodialysis patients.

BACKGROUND: Hypoalbuminemia is a powerful predictor of morbidity and mortality in hemodialysis (HD) patients and results from a reduction in albumin synthesis. It is not known if this is associated with any impairment of the normal response to feeding. METHODS: Protein turnover and albumin synthesis were measured in the fasting and fed state using a primed constant infusion of L-[1-(13)C]leucine in seven hypoalbuminemic (albumin < or = 36 g/L) HD patients (HHD), seven normoalbuminemic (albumin > or = 40 g/L) HD patients (NHD) and nine age-matched normal controls. RESULTS: The increase in albumin synthesis on feeding was impaired in HHD patients (fasting 15.0 +/- 1.5 vs. fed 17.7 +/- 2.9%, P = NS) compared to NHD (fasting 13.7 +/- 0.9 vs. fed 17.4 +/- 1.0%, P < 0.05) and controls (fasting 12.9 +/- 0.6 vs. fed 15.2 +/- 0.6%, P < 0.05). In addition, body mass index and percent body fat were significantly (P < 0.05) lower in HHD (20.8 +/- 1.3 kg/m2, 23.4 +/- 2.0%) than NHD (26.7 +/- 1.3 kg/m2, 33.1 +/- 3.2%) or controls (26.2 +/- 1.1 kg/m2, 32.6 +/- 1.8%). There was no difference in dietary protein or energy intake in the three groups. CONCLUSIONS: There are differences of body composition and protein metabolism in HHD patients that may be related to an impaired metabolic response to feeding.