Unlike sleep-walkers, patients with rapid-eye-movement-behaviour disorder (RBD) rarely leave the bed during the re-enactment of their dreams. RBD movements may be independent of spatial co-ordinates of the ‘outside-world’, and instead rely on (allocentric) brain-generated virtual space-maps, as evident by patients’ limited truncal/axial movements. To confirm this, a semiology analysis of video-polysomnography records of 38 RBD patients was undertaken and paradoxically restricted truncal/thoraco-lumbar movements during complex dream re-enactments demonstrated.
Background Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes. Methods/design A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events. Discussion This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy. Trial registration ISRCTN 56898625 Registration Date: 10 April, 2018.
The intensive care unit (ICU) is a complex environment where patients, family members and healthcare professionals have their own personal experiences. Improving ICU experiences necessitates the involvement of all stakeholders. This holistic approach will invariably improve the care of ICU survivors, increase family satisfaction and staff wellbeing, and contribute to dignified end-of-life care. Inclusive and transparent participation of the industry can be a significant addition to develop tools and strategies for delivering this holistic care. We present a report, which follows a round table on ICU experience at the annual congress of the European Society of Intensive Care Medicine. The aim is to discuss the current evidence on patient, family and healthcare professional experience in ICU is provided, together with the panel’s suggestions on potential improvements. Combined with industry, the perspectives of all stakeholders suggest that ongoing improvement of ICU experience is warranted.
Purpose Critical Care Outreach Teams (CCOTs) have been associated with improved outcomes in patients with haematological malignancy (HM). This study aims to describe CCOT activation by patients with HM before and during the Covid-19 pandemic, assess amny association with worse outcomes, and examine the psychological impact on the CCOT. Materials and methods A retrospective, mixed-methods analysis was performed in HM patients reviewed by the CCOT over a two-year period, 01 July 2019 to 31 May 2021. Results The CCOT increased in size during the surge period and reviewed 238 HM patients, less than in the pre- and post-surge periods. ICU admission in the baseline, surge and the non-surge periods were 41.7%, 10.4% and 47.9% respectively. ICU mortality was 22.5%, 0% and 21.7% for the same times. Time to review was significantly decreased (p = 0.012). Semi-structured interviews revealed four themes of psychological distress: 1) time-critical work; 2) non-evidence based therapies; 3) feelings of guilt; 4) increased decision-making responsibility. Conclusions Despite the increase in total hospital referrals, the number of patients with HM that were reviewed during the surge periods decreased, as did their ICU admission rate and mortality. The quality of care provided was not impaired, as reflected by the number of patients receiving bedside reviews and the shorter-than-pre-pandemic response time.
Background The UK’s “Getting It Right First Time” programme recommends that management of people with fibromyalgia should centre on primary care. However, it remains unclear as to how best to organise health systems to deliver services to optimise patient outcomes. Aim To profile UK healthcare services for people with fibromyalgia: provision of National Health Services (NHS) and use of non-NHS services by people with fibromyalgia. Methods Two online open surveys (A and B) incorporating questions about diagnosis, treatment and management of fibromyalgia and gaps in healthcare services were conducted between 11th September 2019 and 3rd February 2020. These were targeted to NHS healthcare professionals consulting with people with fibromyalgia (Survey A) and people ≥16 years diagnosed with fibromyalgia using non-NHS services to manage their condition (Survey B). Descriptive statistics were used to report quantitative data. Thematic analysis was undertaken for qualitative data. Results Survey A received 1701 responses from NHS healthcare professionals across the UK. Survey B received 549 responses from people with fibromyalgia. The results show that NHS services for people with fibromyalgia are highly disparate, with few professionals reporting care pathways in their localities. Diagnosing fibromyalgia is variable among NHS healthcare professionals and education and pharmacotherapy are mainstays of NHS treatment and management. The greatest perceived unmet need in healthcare for people with fibromyalgia is a lack of available services. From the pooled qualitative data, three themes were developed: ‘a troublesome label’, ‘a heavy burden’ and ‘a low priority’. Through the concept of candidacy, these themes provide insight into limited access to healthcare for people with fibromyalgia in the UK. Conclusion This study highlights problems across the NHS in service provision and access for people with fibromyalgia, including several issues less commonly discussed; potential bias towards people with self-diagnosed fibromyalgia, challenges facing general practitioners seeking involvement of secondary care services for people with fibromyalgia, and a lack of mental health and multidisciplinary holistic services to support those affected. The need for new models of primary and community care that offer timely diagnosis, interventions to support self-management with access to specialist services if needed, is paramount.
Background and objectives: Daprodustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) being investigated for the treatment of anemia of CKD. In this noninferiority trial, we compared daprodustat administered three times weekly with epoetin alfa (epoetin) in patients on prevalent hemodialysis switching from a prior erythropoiesis-stimulating agent (ESA). Design, setting, participants, & measurements: Patients on hemodialysis with a baseline hemoglobin of 8-11.5 g/dl receiving an ESA were randomized 2:1 to daprodustat three times weekly (n=270) or conventional epoetin (n=137) for 52 weeks. Dosing algorithms aimed to maintain hemoglobin between 10 and 11 g/dl. The primary end point was mean change in hemoglobin from baseline to the average during the evaluation period (weeks 28-52). The principal secondary end point was average monthly intravenous iron dose. Other secondary end points included BP and hemoglobin variability. Results: Daprodustat three times weekly was noninferior to epoetin for mean change in hemoglobin (model-adjusted mean treatment difference [daprodustat-epoetin], -0.05; 95% confidence interval, -0.21 to 0.10). During the evaluation period, mean (SD) hemoglobin values were 10.45 (0.55) and 10.51 (0.85) g/dl for daprodustat and epoetin groups, respectively. Responders (defined as mean hemoglobin during the evaluation period in the analysis range of 10 to 11.5 g/dl) were 80% in the daprodustat group versus 64% in the epoetin group. Proportionately fewer participants in the daprodustat group versus the epoetin group had hemoglobin values either below 10 g/dl or above 11.5 g/dl during the evaluation period. Mean monthly intravenous iron use was not significantly lower with daprodustat versus epoetin. The effect on BP was similar between groups. The percentage of treatment-emergent adverse events was similar between daprodustat (75%) and epoetin (79%). Conclusions: Daprodustat was noninferior to epoetin in hemoglobin response and was generally well tolerated. Clinical trial registry name and registration number: Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Three Times Weekly Dosing in Dialysis (ASCEND-TD), NCT03400033.
Background Beneficial response to first-line immunosuppressive azathioprine in patients with inflammatory bowel disease (IBD) is low due to high rates of adverse events. Co-administrating allopurinol has been shown to improve tolerability. However, data on this co-therapy as first-line treatment are scarce.AimRetrospective comparison of long-term effectiveness and safety of first-line low-dose azathioprine-allopurinol co-therapy (LDAA) with first-line azathioprine monotherapy (AZAm) in patients with IBD without metabolite monitoring.Methods Clinical benefit was defined as ongoing therapy without initiation of steroids, biologics or surgery. Secondary outcomes included CRP, HBI/SCCAI, steroid withdrawal and adverse events.ResultsIn total, 166 LDAA and 118 AZAm patients (median follow-up 25 and 27 months) were evaluated. Clinical benefit was more frequently observed in LDAA patients at 6 months (74% vs. 53%, p = 0.0003), 12 months (54% vs. 37%, p = 0.01) and in the long-term (median 36 months; 37% vs. 24%, p = 0.04). Throughout follow-up, AZAm patients were 60% more likely to fail therapy, due to a higher intolerance rate (45% vs. 26%, p = 0.001). Only 73% of the effective AZA dose was tolerated in AZAm patients, while LDAA could be initiated and maintained at its target dose. Incidence of myelotoxicity and elevated liver enzymes was similar in both cohorts, and both conditions led to LDAA withdrawal in only 2%. Increasing allopurinol from 100 to 200–300 mg/day significantly lowered liver enzymes in 5/6 LDAA patients with hepatotoxicity.Conclusions Our poor AZAm outcomes emphasize that optimization of azathioprine is needed. We demonstrated a long-term safe and more effective profile of first-line LDAA. This co-therapy may therefore be considered standard first-line immunosuppressive.
Introduction Craniopharyngiomas are benign tumours mainly confined to the cranial cavity in the suprasellar region. Research Question and Case Description: We present a rare case of an aggressive papillary craniopharyngioma with disseminated spinal intradural disease. A 67-year-old woman presented with a 4-month history of headache, visual disturbance, acute confusion and radicular leg pain. Previous history of breast carcinoma (ER + PR + HER2-) was noted. The importance of histological diagnosis prior to treatment of sellar/suprasellar lesions with atypical or aggressive features is explored. Material and methods MRI demonstrated a partly solid and partly cystic pituitary mass lesion in the sellar and suprasellar region with chiasmal compression and hypothalamic involvement. The sella was mildly enlarged and there were no calcifications. Whole neuraxis MRI revealed intradural deposits involving the ventricular system, spinal cord and conus. Within a month, the lesion rapidly increased in size. The patient underwent a craniotomy and transventricular resection of the sellar and suprasellar mass. Cranial lesion histology favoured papillary craniopharyngioma, confirmed by BRAF V600 mutation. Lumbar puncture CSF cytology confirmed craniopharyngioma with BRAF mutation and no evidence of metastatic breast cancer. Results The patient remained confused postoperatively without focal neurological deficit and underwent palliative whole brain radiotherapy. She died 4 months later. A review of the literature identified 29 reports of ruptured craniopharyngioma. Discussion and Conclusion; Ruptured craniopharyngioma presents with a suprasellar mass and drop lesions in the spinal canal, characteristics radiologically indistinguishable from metastatic disease. The importance of histological diagnoses in directing the management of these cases is highlighted.
Paediatric acute liver failure (PALF) is defined as a biochemical evidence of acute liver injury in a child with no previous history of chronic liver disease characterised by an international normalised ratio (INR) of 1·5 or more unresponsive to vitamin K with encephalopathy, or INR of 2·0 or more with or without encephalopathy. PALF can rapidly progress to multiorgan dysfunction or failure. Although the transplant era has substantially changed the outlook for these patients, transplantation itself is not without risks, including those associated with life-long immunosuppression. Consequently, there has been an increased focus on improving medical management to prioritise bridging of patients to native liver survival, which is possible due to improved understanding of the underlying pathophysiology of multiorgan involvement in PALF. In this Review, we discuss recent advances in the medical management of PALF with an aim of reducing the need for liver transplantation. The Review will focus on the non-specific immune-mediated inflammatory response, extracorporeal support devices, neuromonitoring and neuroprotection, and emerging cellular and novel future therapeutic options.
The use of inhaled nitric oxide (iNO) in treating pulmonary hypertension in infants with congenital diaphragmatic hernia (CDH) is controversial. Our aims were to identify factors associated with survival in CDH infants and whether this was influenced by the response to iNO. Results of CDH infants treated in a tertiary surgical and medical perinatal centre in a ten year period (2011–2021) were reviewed. Factors affecting survival were determined. To assess the response to iNO, blood gases prior to and 30 to 60 min after initiation of iNO were analysed and PaO2/FiO2 ratios and oxygenation indices (OI) calculated. One hundred and five infants were admitted with CDH; 46 (43.8%) infants died. The CDH infants who died had a lower median observed to expected lung to head ratio (O/E LHR) (p < 0.001) and a higher median highest OI on day 1 (HOId1) (p < 0.001). HOId1 predicted survival after adjusting for gestational age, Apgar score at 5 min and O/E LHR (odds ratio 0.948 (95% confidence intervals 0.913–0.983)). Seventy-two infants (68.6%) received iNO; 28 survived to discharge. The median PaO2 (46.7 versus 58.8 mmHg, p < 0.001) and the median PaO2/FiO2 ratio (49.4 versus 58.8, p = 0.003) improved post iNO initiation. The percentage change in the PaO2/FiO2 ratio post iNO initiation was higher in infants who survived (69.4%) compared to infants who died (10.2%), p = 0.018. Conclusion: The highest OI on day 1 predicted survival. iNO improved oxygenation in certain CDH infants and a positive response was more likely in those who survived.
Background Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics. Methods This is a prospective, double-blind multicentre randomised controlled trial (RCT) including 75 non-dialysis stage 3–4 CKD patients with iron deficiency but without anaemia. Patients were randomly (1:1) assigned to either: i) intravenous iron therapy, or ii) placebo, with concurrent recruitment of eight CKD non-iron deficient participants and six healthy volunteers. The primary outcome of the study is the six-minute walk test (6MWT) distance between baseline and four-weeks. An additional exercise training programme for patients in both groups was initiated and completed between 4 and 12 weeks, to determine the effect of iron repletion compared to placebo treatment in the context of patients undertaking an exercise programme. Additional secondary outcomes include fatigue, physical function, muscle strength, muscle metabolism, quality of life, resting blood pressure, clinical chemistry, safety and harms associated with the iron therapy intervention and the exercise training intervention, and hospitalisations. All outcomes were conducted at baseline, 4, and 12 weeks, with a nested qualitative study, to investigate the experience of living with iron deficiency and intervention acceptability. The cohort have been recruited and baseline assessments undertaken. Results Seventy-five individuals were recruited. 44% of the randomised cohort were male, the mean (SD) age was 58 (14) years, and 56% were White. Body mass index was 31 (7) kg/m ² ; serum ferritin was 59 (45) μg/L, transferrin saturation was 22 (10) %, and haemoglobin was 125 (12) g/L at randomisation for the whole group. Estimated glomerular filtration rate was 35 (12) mL/min/1.73 m ² and the baseline 6MWT distance was 429 (174) m. Conclusion The results from this study will address a substantial knowledge gap in the effects of intravenous iron therapy, and offer potential clinical treatment options, to improve exercise capacity, physical function, fatigue, and muscle metabolism, for non-dialysis patients with CKD who are iron-deficient but not anaemic. It will also offer insight into the potential novel effects of an 8-week exercise training programme. Trial registration EudraCT: 2018–000,144-25 Registered 28/01/2019.
Observational studies have investigated the effectiveness and safety of Direct Oral Anticoagulants (DOACs) and Vitamin K antagonists (VKA) used in Non‐Valvular Atrial Fibrillation. We performed a systematic review and meta‐analysis assessing the risk of ischemic stroke, Thromboembolism (TE) and Intracranial Hemorrhage (ICH) associated with the use of DOACs and VKA. Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age, and gender were performed. A random‐effects model was used. We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke [HR: 0.82, 95% CI: 0.68‐0.99] compared to Dabigatran. Rivaroxaban was associated with lower risk of stroke [HR: 0.90, 95% CI: 0.83‐0.98] compared to VKA. Dabigatran [HR: 0.85, 95% CI: 0.80‐0.91], Rivaroxaban [HR: 0.83, 95% CI: 0.77‐0.89] and Apixaban [HR: 0.75, 95% CI: 0.65‐0.86] were associated with lower risk for TE/stroke compared to VKA. Apixaban [HR: 1.32, 95% CI: 1.03‐1.68] and Rivaroxaban [HR: 1.58, 95% CI: 1.31‐1.89] were associated with higher risk of ICH compared to Dabigatran. Dabigatran [HR: 0.48, 95% CI: 0.44‐0.52], Apixaban [HR: 0.60, 95% CI: 0.49‐0.73] and Rivaroxaban [HR: 0.73, 95% CI: 0.65‐0.81] were associated with lower risk of ICH compared to VKA. Our study demonstrated significant differences in the risk of ischemic stroke, TE/stroke, and ICH associated with individual DOACs compared to both other DOACs and VKA.
Non‐motor fluctuations (NMF) in people with Parkinson's disease (PwP) are clinically important yet understudied. To study NMF in PwP using both the Movement Disorder Society Non‐Motor Rating Scale (MDS‐NMS) NMF subscale and wearable sensors. We evaluated differences in overall burden of NMF and of specific NMF across disease durations: <2 years (n=33), 2‐5 years (n=35), 5‐10 years (n=33), and >10 years (n=31). In addition, wearable triaxial sensor output was used as an exploratory outcome for early morning “off” periods. Significant between‐group differences were observed for MDS‐NMS NMF total scores (p<0.001), and specifically for depression, anxiety, fatigue and cognition, with both NMF prevalence and burden increasing in those with longer disease duration. Whereas only 9.1% with a short disease duration had NMF (none of whom had dyskinesia), in PwP with a disease duration of >10 years this was 71.0% (p<0.001). From a motor perspective, dyskinesia severity increased evenly with increasing disease duration, while NMF scores in affected individuals showed an initial increase with largest differences between 2‐5 years disease duration (p<0.001), with plateauing afterwards. Finally, we observed that the most common NMF symptoms in patients with sensor‐confirmed early morning “off” periods were fluctuations in cognitive capabilities, restlessness, and excessive sweating. NMF prevalence in PwP increases with disease duration, but in a pattern different from motor fluctuations. Moreover, NMF can occur in PwP without dyskinesia, and in those with NMF the severity of NMF increases most during years 2‐5 after diagnosis. This article is protected by copyright. All rights reserved.
In April 2022, an increased incidence of acute hepatitis cases of unknown aetiology among previously healthy children across the United Kingdom was described. Since, more than 200 cases from United Kingdom and hundreds more from all across the world have been reported. The majority of affected children were younger than six years of age. The clinical presentation was nonspecific with diarrhoea and vomiting usually preceding the appearance of jaundice, abdominal pain, nausea and malaise. Approximately 10% have required liver transplantation. An infectious aetiology has been considered likely given the epidemiological and clinical features of the reported cases. More than 60% of the children tested were diagnosed with adenovirus infection although a clear aetiological connection has still to be demonstrated. No link with SARS-CoV-2 infection and COVID-19 vaccine was found. What is not clear to date is whether the high number of acute hepatitis cases reported is related to a true increase in incidence or heightened awareness following on from the initial reports from the United Kingdom. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition developed a paper on the current outbreak of acute hepatitis of unknown aetiology recognizing its importance and the need of approaching the current situation with a scientifically rigorous approach. The aims of the paper are to summarize the current knowledge and to identify the most pertinent issues regarding the diagnosis and management of this condition and the research questions raised.
Introduction: Fibromyalgia guidelines recommend multi-modal, non-pharmacological interventions but there is limited evidence on the optimal programme. The Fibromyalgia Active Management and Exercise programme (FAME) aimed to improve function and quality of life. It consisted of 12 sessions delivered by a multidisciplinary team and incorporated education, exercise, Cognitive Behavioural Therapy and mindfulness approaches. This qualitative service evaluation explored the experience and acceptability of FAME from the perspective of the patients' and healthcare practitioners' (HCP). Methods: All patients and HCP involved in the first FAME programme were invited to attend either one audio-recorded focus group or an individual semi-structured interview. Topic guides were developed a priori. Data were transcribed verbatim and analysed thematically. Results: Thirteen participants (six HCP (three physiotherapists, two nurses, one psychologist)) and seven patients (mean age 46 (7.5) years, all female,) were enroled. FAME was acceptable to HCP participants but not to all patient participants. Where patient participants understood and anticipated the aims of FAME, the programme was found to be acceptable. Whereas, patient participants who did not fully understand the aims of the programme reported lower acceptability. Three themes were generated: expectations and preparation for FAME, the value of social support, and FAME as a learning opportunity. The themes could be explained by five constructs of the Theoretical Framework of Acceptability. Conclusion: FAME was acceptable to HCPs but not to all patient participants. Patient and HCP participants valued social support and regarded this as central to their learning. Further adaptation of FAME is required to optimise acceptability.
Abstract Purpose Intramedullary spinal cord tumours (IMSCTs) are comparatively rare neoplasms. We present a single-centre clinical case series of adult patients with surgically managed IMSCTs. Methods We performed a retrospective analysis of electronic patient records in the time period spanning July 2010 to July 2021. All adult patients that had undergone surgical management for IMSCTs were eligible for inclusion. Baseline and post-operative clinical and radiological characteristics, along with follow-up data, were assessed. We also performed a literature review with a focus on surgical outcomes for IMSCTs. Results Sixty-six patients matched our selection criteria, with a median age of 42 years (range 23–85). Thirty-four ependymomas, 17 haemangioblastomas, 12 astrocytomas, 2 lymphomas and 1 teratoma were included. Statistical analysis yielded several significant findings: IMSCTs spanning a greater number of vertebral levels are significantly associated with poor McCormick outcomes (p = 0.03), presence of gait disturbance before surgery is significantly associated with poor outcome for both post-operative McCormick and Nurick scores (p = 0.007), and radicular pain present pre-operatively is significantly associated with a good post-operative McCormick score (p = 0.045). Haemangioblastomas are significantly more likely to have a clear intra-operative dissection plane compared to ependymomas and astrocytomas (p = 0.009). However, astrocytomas have a significantly higher prevalence of good McCormick outcomes compared to ependymomas and haemangioblastomas (p = 0.03). Conclusion Histological diagnosis, cranio-caudal extent of the tumour and the presence or absence of baseline deficits—such as gait impairment and radicular pain—are significant in determining neurological outcomes after surgery for IMSCTs.
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