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Evaluating the return of additional findings from the 100,000 Genomes Project: A mixed methods study exploring participant experiences of receiving secondary findings from genomic sequencing
No full textPURPOSE: 100,000 Genomes Project participants could consent to receive additional findings (AFs) for variants associated with susceptibility to cancer and familial hypercholesterolemia (FH). Here we evaluate stakeholder experiences to inform clinical practice. METHODS: Mixed-methods study conducted at 18 sites across England that comprised a cross-sectional survey and interviews with participants who received a positive AF (PAF), and interviews with participants who had no AFs (NAF). RESULTS: There were 146 surveys followed by 35 interviews with PAF participants, and 29 interviews with NAF participants. Surveys found that PAF results were seen as useful and would influence health management (82%). Most (90%) had shared their result with family members. Experiences differed by PAF type; cancer PAF participants were often initially shocked and anxious, and found telling family members challenging compared to participants with an FH PAF. Whilst most experiences of NAF results were positive, some misunderstandings were identified. Participants supported returning AFs when offering genome sequencing. CONCLUSION: Patient experiences of receiving AFs were primarily positive and there is support for offering AFs routinely. Considerations for offering AFs in clinical practice include adapting approaches tailored to individual conditions and greater support for people with a NAF result.CC BY 4.0 Internationa
Protocol update for the UK cohort study to investigate the prevention of parastomal hernia (the CIPHER study)
No full textCC BY 4.0 (Creative Commons Attribution
Severe Asthma Questionnaire (SAQ) and Asthma Control Questionnaire (ACQ) as Early Predictors of Biologic Response in Severe Asthma
No full textBACKGROUND: Biologic therapy in asthma can be life-changing and affect health-related quality of life, but symptoms are rarely used in the assessment of response. AIM: To examine the change in health-related quality of life and asthma control between starting a biologic and assessment of biologic response, assessing whether this change can provide early prediction of eventual clinical response at 12 months. METHODS: A service evaluation of severe asthmatics initiating a biologic at the Royal Devon NHS trust between 2019 and 22. Health-Related Quality of Life (Severe Asthma Questionnaire) and asthma control (Asthma Control Questionnaire-6) was captured at baseline, 8 weeks, 16 weeks and 12 months. Patients were classified as responder or non-responder using NICE Criteria for biologic response. Independent samples t-tests were used to determine statistical difference in change from baseline patient reported outcome measure scores between responder and non-responders. RESULTS: One hundred and eight initiations (103 patients) of biologic therapy were included. At 8 weeks and 16 weeks, responders had greater improvement in Severe Asthma Questionnaire & Severe Asthma Questionnaire Global compared to non-responders (p<0.05). Improvement in Asthma Control Questionnaire only achieved significance between all-responders and non-responders at 16 weeks (p<0.05). CONCLUSION: This study provides evidence of the early and sustained improvement in health-related quality of life and symptoms after starting biologic therapy. The findings support the use of the Severe Asthma Questionnaire and the Asthma Control Questionnaire as per the Core Outcome Measures Sets for Severe Asthma (COMSA). We have shown that health-related quality of life and asthma control can assist earlier assessment of response and non-response to biologics.CC BY 4.0 (Creative Commons Attribution
Dietary interventions for the management of type 2 diabetes mellitus in childhood and adolescence: A systematic review
No full textAIMS: Despite the alarming increasing incidence of type 2 diabetes mellitus (T2DM) in children and young People (CYP), and its associated morbidities and poor long-term prognosis, there remains uncertainty in its management. Dietary interventions have been shown to be effective in adults with T2DM, but little is known about their effectiveness in CYP. The aim of this systematic review is to provide up-to-date evidence regarding dietary interventions for T2DM in childhood and adolescence. METHODS: Five databases Embase, MEDLINE, CENTRAL, Web of Science and CINAHL were searched from January 2000 to May 2023 for all studies involving dietary interventions in CYP under 19 years with T2DM. The primary outcome was glycaemic control as measured by HbA1c. RESULTS: Of 8352 search results, five papers met inclusion criteria. No randomised controlled trials were identified. Two interventional studies (n = 28) found very low energy diets (VLED) were associated with reduced HbA1c (16 mmol/mol (3.6%) reduction after 8 weeks), decreased requirement for pharmacotherapy and weight loss. However, benefits to HbA1c were not sustained over 2 years. From the observational studies, the most frequent self-reported dietary strategies were limiting sweets and increasing fruit/vegetable intake, but efficacy was limited. Limiting fat intake was associated with improved HbA1c in women. CONCLUSIONS: There is limited evidence and a lack of robust clinical trials to support the effectiveness of dietary interventions for CYP-onset T2DM. With evidence of benefit in adulthood and encouraging initial results in the young, it is imperative that fully powered randomised trials with longer follow-up are undertaken to determine efficacy.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Implementation of a national AI technology program on cardiovascular outcomes and the health system
No full textCoronary artery disease (CAD) is a major cause of ill health and death worldwide. Coronary computed tomographic angiography (CCTA) is the first-line investigation to detect CAD in symptomatic patients. This diagnostic approach risks greater second-line heart tests and treatments at a cost to the patient and health system. The National Health Service funded use of an artificial intelligence (AI) diagnostic tool, computed tomography (CT)-derived fractional flow reserve (FFR-CT), in patients with chest pain to improve physician decision-making and reduce downstream tests. This observational cohort study assessed the impact of FFR-CT on cardiovascular outcomes by including all patients investigated with CCTA during the national AI implementation program at 27 hospitals (CCTA n = 90,553 and FFR-CT n = 7,863). FFR-CT was safe, with no difference in all-cause (n = 1,134 (3.2%) versus 1,612 (2.9%), adjusted-hazard ratio (aHR) 1.00 (0.93-1.08), P = 0.97) or cardiovascular mortality (n = 465 (1.3%) versus 617 (1.1%), aHR 0.96 (0.85-1.08), P = 0.48), while reducing invasive coronary angiograms (n = 5,720 (16%) versus 8,183 (14.9%), aHR 0.93 (0.90-0.97), P < 0.001) and noninvasive cardiac tests (189/1,000 patients versus 167/1,000), P < 0.001). Implementation of an AI-diagnostic tool as part of a health intervention program was safe and beneficial to the patient pathway and health system with fewer cardiac tests at 2 years.CC BY 4.0 (Creative Commons Attribution
Heart Failure Masked as Pulmonary Embolism in Non-adherent Patient With Atrial Fibrillation: Case Report and Analytical Review of the Literature
No full textBACKGROUND/AIM: Atrial fibrillation (AF) and heart failure (HF) commonly co-occur, significantly increasing morbidity and mortality. Poorly controlled AF can contribute to complications like HF and is associated with conditions, such as stroke and pulmonary embolism (PE). This report involves a man with AF who had persistent respiratory symptoms and left-sided chest pain, initially suspected to be PE, but eventually diagnosed as HF. CASE REPORT: A 43-year-old male experienced increasing breathlessness, cough, and fatigue. Initially suspected to have a respiratory infection, his persistent symptoms raised concern for PE. The patient had a history of AF, unsuccessful cardioversion, and long-term non-adherence to beta blockers. Initial assessment revealed persistent respiratory symptoms and elevated levels of C-reactive protein, D-dimer, N-terminal pro-B-type natriuretic peptide, and Troponin T. Chest X-ray showed pulmonary congestion, and echocardiogram confirmed a severely impaired ejection fraction (EF <20%). While the differential diagnosis included community-acquired pneumonia, PE, and HF, the final diagnosis was worsening AF and HF with reduced EF, not PE. CONCLUSION: PE symptoms can overlap with HF, making careful differential diagnosis essential, particularly in AF patients with elevated D-dimer levels, where false positives necessitate caution. This case underscores the importance of thorough differential diagnosis and clinical judgment before ordering tests to avoid misdiagnosis. Long-term non-adherence to beta blockers exacerbated the patient's symptoms, emphasising the critical role of consistent medication use in managing AF and preventing complications like HF. This case report also highlights the importance of thorough investigations, guideline-based treatments and multidisciplinary care in complex AF-HF cases.This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international licenseRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Supporting the bereaved child in the adult ICU: let's take the first step! Author's reply
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Management of severe and fulminant Clostridioides difficile infection in adults
No full textClostridioides difficile (formerly known as Clostridium difficile) is a significant cause of healthcare-associated infection with symptoms ranging from diarrhoea and abdominal pain to pseudomembranous colitis and toxic megacolon. Severe disease can pose a significant morbidity and mortality risk and is to be considered a medical emergency. The emergence of a new C. difficile ribotype with an estimated mortality rate of 20% (ribotype 995) has prompted a re-review of the evidence and guidelines around managing severe C. difficile infections (CDI). International guidance on the management of CDI varies regarding first-line antibiotic choice. Metronidazole is no longer favoured as first line due to concerns around resistance, and vancomycin and fidaxomicin are now recommended as first line options. Antibiotic therapy should be used in conjunction with good supportive measures and early consideration of surgical management. Faecal microbiota transplant can be utilized in recurrent CDI and may be useful in severe disease. Severe CDI is a significant ongoing threat to public health, and further research into effective management is essential to ensure the best possible outcomes for patients.CC BY 4.0 (Creative Commons Attribution
Treatment options to support the elimination of hepatitis C: an open-label, factorial, randomised controlled non-inferiority trial
No full textBACKGROUND: WHO recommends treating hepatitis C infection with one of three antiviral combinations for 8-12 weeks. No randomised trials have compared these regimens, and high cure rates might be achievable with shorter durations of therapy. We aimed to compare sofosbuvir-daclatasvir with sofosbuvir-velpatasvir, and to evaluate potential novel treatment strategies. METHODS: We conducted a multi-arm, open-label, randomised controlled non-inferiority trial in two public hospitals in Viet Nam. Adults (aged ≥18 years) with chronic hepatitis C infection and mild-to-moderate liver fibrosis were eligible. Recruitment was stratified by centre and viral genotype (1-5 vs 6) with 1:1 random allocation to an oral fixed-dose combination of sofosbuvir 400 mg plus daclatasvir 60 mg (sofosbuvir-daclatasvir) or sofosbuvir 400 mg plus velpatasvir 100 mg (sofosbuvir-velpatasvir). Participants were simultaneously factorially randomly assigned to one of four treatment strategies: 12 weeks' standard of care (SOC); 4 weeks' therapy with four weekly PEGylated interferon alfa-2a subcutaneous injections; induction and maintenance therapy with 2 weeks' standard therapy followed by 10 weeks' therapy 5 days a week; and response-guided therapy (RGT) for 4, 8, or 12 weeks determined by viral load on day 7. The primary outcome was sustained virological response (SVR) 12 weeks after treatment completion, analysed in all evaluable participants regardless of actual treatment received. We chose a 5% non-inferiority margin for the drug comparison, and a 10% non-inferiority margin for the treatment strategy comparisons. Safety was assessed in all randomised participants. This trial is registered with ISRCTN, 61522291, and is completed. FINDINGS: Between June 19, 2020, and May 10, 2023, 624 participants were randomised (470 [75%] were male and 154 [25%] were female). 296 (47%) had genotype 6 and 328 (53%) had genotypes 1-5. The primary outcome was assessable in 609 (98%) participants. SVR occurred in 294 (97%) of 302 participants in the sofosbuvir-daclatasvir group and 292 (95%) of 307 participants in the sofosbuvir-velpatasvir group (risk difference 2·2%, 90% credible interval [CrI] -0·2 to 4·8, within the 5% non-inferiority margin; 93% probability that sofosbuvir-daclatasvir is superior to sofosbuvir-velpatasvir). SVR occurred in 148 (99%) of 150 in the SOC group, 143 (94%) of 152 in the 4-week antiviral plus interferon group (-4·5%, 90% CrI -8·3 to -1·3), 151 (99%) of 152 in the induction-maintenance group (0·6%, -1·1 to 2·7), and 144 (93%) of 155 in the RGT group (-5·7%, -9·6 to -2·3); all risk differences were within the 10% non-inferiority margin. Serious adverse events were rare (11 [4%] of 313 participants in the sofosbuvir-velpatasvir group vs six [2%] of 311 in the sofosbuvir-daclatasvir group; risk difference -1·6% [95% CrI -4·2 to 0·8]) with no evidence of differences between regimens or strategies, but adverse reactions were very common in the 4-week antiviral plus interferon group compared with the other treatment strategies (risk difference vs SOC group, 66·8% [59·2 to 74·0]; p<0·0001). INTERPRETATION: Sofosbuvir-daclatasvir was non-inferior to sofosbuvir-velpatasvir. High efficacy was seen with novel strategies, which might help to inform approaches to treatment for harder-to-reach populations. FUNDING: Wellcome Trust.CC BY 4.0 (Creative Commons Attribution
Intravascular Shockwave Lithotripsy for the Treatment of Severe Peripheral Arterial Disease: A Single-Centre Experience
No full textBackground Chronic limb-threatening ischemia (CLTI) is the most severe manifestation of peripheral arterial disease. Various revascularization techniques are employed to treat peripheral arterial disease. Intravascular shockwave lithotripsy (IVL) is a relatively new procedure for the treatment of calcific lower limb peripheral arterial diseases (PAD). Objectives To assess the effectiveness and safety of shockwave lithotripsy in patients with severe PAD through an evaluation of limb salvage rate and patient survival. Methods A retrospective study of all patients treated with shockwave lithotripsy between November 2019 and June 2024 was performed. The primary outcome was amputation-free survival and secondary outcomes were potential complications of IVL (thrombo-embolization, perforation, and restenosis). Patients were followed up in the clinic and assessed both clinically and with a duplex scan at three months. Results A total of 38 patients were included in the study. The median age was 71 years; 28 were males. Among the patients, 28 (73.68%) were diabetic, 4 patients (10.53%) were current smokers, 10 patients (26.32%) were ex-smokers, and 24 patients (63.16%) were non-smokers. According to the Rutherford classification of PAD, 33 of the 38 patients were in stages 4-6. Only five patients were stage 3. Total number of treated arteries was 47. Treated lesions were 49% in the superficial femoral artery (SFA), 36% in the popliteal artery, 8% in the common femoral artery (CFA), 4% received treatment of the iliac arteries, and 2% of the posterior tibial artery. All treated arteries showed improved angiographic results. Four patients (10.53%) developed distal embolization. No perforation was recorded, and no significant flow-limiting dissection was recorded to require treatment. At the three-month follow-up, imaging revealed improvement in 58% of patients while 5% showed no improvement. Notably, follow-up imaging was not conducted in 37% of patients due to evident clinical improvement such as ulcer healing, palpable pulses, and the presence of Doppler signals. Seven patients required reintervention within three months after the initial IVL operation and 4 patients got revascularized after this period resulting in 11 patients requiring revascularisation after the initial operation. Amputation-free survival was 79% (30 patients). Conclusion Shockwave lithotripsy is associated with a high limb salvage rate and low complication rate. Further research is needed into long-term effectiveness and the role of shockwave treatment as an adjuvant to traditional revascularization techniques of patients with CLTI and short-distance claudicants.This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted