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Systematic Review on the Worldwide Disparities in the Frequency and Results of Emergency Medical Services (EMS) and Response to Out-of-Hospital Cardiac Arrest (OHCA)
No full textThis systematic analysis aimed to analyze the key patterns and tendencies regarding bystander interventions, emergency medical service (EMS) systems, dispatcher support, regional and temporal differences, and the influence of national efforts on survival rates in out-of-hospital cardiac arrest (OHCA). The studies published between 2010 and 2024 examining outcomes of OHCA, interventions by bystanders, and variables linked to OHCA were included in this research. The inclusion process was done under Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), where publications (n = 24) from various geographical locations, including a wide range of research methodologies, were included for this research. The thematic analysis used for the data analysis shows that bystander cardiopulmonary resuscitation (CPR) enhances the chances of survival. The effectiveness of the EMS system, the assistance offered by dispatchers, and the inclusion of doctors in ambulance services are essential components in the management of OHCA. Regional and temporal variations highlight disparities in resuscitation protocols, emphasizing the need for adaptable approaches. Observations from statewide endeavors emphasize the impact of these activities in fostering a culture of prompt bystander intervention. This systematic review presents a comprehensive analysis of research conducted globally, providing a thorough insight into the variables that influence survival rates in instances of OHCA. The review recognizes the importance of bystander CPR and effective EMS services, while also bringing novel perspectives, such as gender disparities and geographical variations that contribute to the existing body of research. Despite possible variances in the studies and biases, the findings underscore the need for tailored therapies and ongoing research to optimize strategies for controlling OHCA and improving survival rates.UnknownRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Uterine artery embolization vs myomectomy for the management of women with uterine leiomyomas: a systematic review and meta-analysis
No full textOBJECTIVE: This study aimed to investigate whether uterine artery embolization offers a better quality of life than myomectomy in premenopausal women diagnosed with leiomyomas of the uterus. DATA SOURCES: A literature search was performed using the electronic databases of PubMed and Cochrane Central Register of Controlled Trials from inception to January 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing uterine artery embolization with myomectomy in women of premenopausal age suffering from uterine leiomyomas were considered. METHODS: The primary outcome was quality of life. The secondary outcomes were reintervention rate and timing, successful pregnancy, stillbirth and miscarriage, cesarean delivery on delivery, and perioperative morbidity. Moreover, time-to-event and standard pairwise meta-analyses were performed, as appropriate. The certainty of the evidence was assessed in line with the Grading of Recommendations, Assessment, Development, and Evaluations methodology. RESULTS: A total of 6 randomized controlled trials met our inclusion criteria. The meta-analysis suggested little to no difference in terms of quality of life between uterine artery embolization and myomectomy (standard mean difference, 0.05; 95% confidence interval, -0.38 to 0.48; I(2)=92%; very low certainty of evidence). Sensitivity analysis, including randomized controlled trials, which included solely myomectomy procedures in the control arm, demonstrated better quality of life for women treated with myomectomy (standard mean difference, -0.32; 95% confidence interval, -0.49 to -0.15; I(2)=15%). Concerning reintervention, myomectomy was likely associated with a decreased risk of future reintervention (risk ratio, 0.32; 95% confidence interval, 0.15-0.69; I(2)=60%; low certainty of evidence) and a more prolonged time interval since a potential reintervention because of recurrence than uterine artery embolization (hazard ratio, 0.41; 95% confidence interval, 0.22-0.77; I(2)=77%; low certainty of evidence). No difference was found between the 2 interventions concerning severe perioperative adverse events (relative risk, 4.13; 95% confidence interval, 0.44-39.20; I(2)=0%; low certainty of evidence). CONCLUSION: Uterine artery embolization is likely associated with increased reintervention rates and less time to reintervention compared with myomectomy in premenopausal women diagnosed with uterine leiomyomas. Evidence suggests no difference between the 2 interventions regarding perioperative morbidity. Uterine artery embolization may exert no effect on quality of life and successful pregnancy; however, the evidence is very uncertain.published versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Pathogenic PDE12 variants impair mitochondrial RNA processing causing neonatal mitochondrial disease
No full textPathogenic variants in either the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial function. Within this group, an increasing number of families have been identified, where Mendelian genetic disorders implicate defective mitochondrial RNA biology. The PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Here, we report that disease-causing PDE12 variants in three unrelated families are associated with mitochondrial respiratory chain deficiencies and wide-ranging clinical presentations in utero and within the neonatal period, with muscle and brain involvement leading to marked cytochrome c oxidase (COX) deficiency in muscle and severe lactic acidosis. Whole exome sequencing of affected probands revealed novel, segregating bi-allelic missense PDE12 variants affecting conserved residues. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing (MPAT-Seq) revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein. Our data suggest that PDE12 regulates mitochondrial RNA processing and its loss results in neurological and muscular phenotypes.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
Utility and limitations of monitoring kidney transplants using capillary sampling
No full textUnknownRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Comparison of Open Surgery and Endovascular Techniques for Juxtarenal and Complex Neck Aortic Aneurysms: The UK COMPlex AneurySm Study (UK-COMPASS) - Peri-operative and Midterm Outcomes
No full textOBJECTIVE: Treatment of juxtarenal and complex neck abdominal aortic aneurysms (AAAs) is now commonly by endovascular rather than open surgical repair (OSR). Published comparisons show poor validity and scientific precision. UK-COMPASS is a comparative cohort study of endovascular treatments vs. OSR for patients with an AAA unsuitable for standard on label endovascular aneurysm repair (EVAR). METHODS: All procedures for AAA in England (November 2017 to October 2019) were identified, AAA anatomy assessed in a Corelab, peri-operative risk scores determined, and propensity scoring used to identify patients suitable for either endovascular treatment or OSR. Patients were stratified by aneurysm neck length (0 - 4 mm, 5 - 9 mm, or = 10 mm) and operative risk; the highest quartile was considered high risk and the remainder standard risk. Death was the primary outcome measure. Endovascular treatments included fenestrated EVAR (FEVAR) and off label standard EVAR (± adjuncts). RESULTS: Among 8 994 patients, 2 757 had AAAs that were juxtarenal, short neck, or complex neck in morphology. Propensity score stratification and adjustment method comparisons included 1 916 patients. Widespread off label use of standard EVAR devices was noted (35.6% of patients). The adjusted peri-operative mortality rate was 2.9%, lower for EVAR (1.2%; p = .001) and FEVAR (2.2%; p = .001) than OSR (4.5%). In standard risk patients with a 0 - 4 mm neck, the mortality rate was 7.4% following OSR and 2.3% following FEVAR. Differences were smaller for patients with a neck length = 5 mm: 2.1% OSR vs. 1.0% FEVAR. At 3.5 years of follow up, the overall mortality rate was 20.7% in the whole study population, higher following FEVAR (27.6%) and EVAR (25.2%) than after OSR (14.2%). However, in the 0 - 4 mm neck subgroup, overall survival remained equivalent. The aneurysm related mortality rate was equivalent between treatments, but re-intervention was more common after EVAR and FEVAR than OSR. CONCLUSION: FEVAR proves notably safer than OSR in the peri-operative period for juxtarenal aneurysms (0 - 4 mm neck length), with comparable midterm survival. For patients with short neck (5 - 9 mm) and complex neck (= 10 mm) AAAs, overall survival was worse in endovascularly treated patients compared with OSR despite relative peri-operative safety. This warrants further research and a re-appraisal of the current clinical application of endovascular strategies, particularly in patients with poor general survival outlook owing to comorbidity and age.Published version, accepted version (12 months embrago)The article is available via Open Access. Click on the 'Additional link' above to access the full-text
I'm quite proud of how we've handled it": health professionals' experiences of returning additional findings from the 100,000 genomes project"
No full textParticipants in the 100,000 Genomes Project (100kGP) could consent to receive additional finding (AF) results, individual variants relating to genes associated with susceptibility to cancer and familial hypercholesterolemia (FH). In the study reported here, qualitative interviews were used to explore the experiences of National Health Service (NHS) professionals from across England who were tasked with returning over 80,000 no AF" results and 700 positive AF results to 100kGP participants. Interviews were conducted with 45 professionals from a range of backgrounds, including Genetic Counsellors, Clinical Geneticists, FH Clinical Nurse Specialists and Clinical Scientists. Interviews were analysed using a codebook thematic analysis approach. Returning AF results has been a significant endeavour, with challenges for pathways, administrative processes and clinical and laboratory time when the capacity of NHS services is already stretched. Professionals discussed going "above and beyond" to prioritise patient care through pathway design, additional clinics, overtime, longer appointments and provision of follow-up appointments. Professionals also described facing practical and emotional challenges when returning AFs. Benefits for patients from receiving AFs in the 100kGP were highlighted and professionals were generally positive about offering clinically actionable AFs within routine NHS clinical care. Professionals were, however, cautious around the implementation of AFs into routine care and felt more research and discussion was needed to determine which AFs to offer, approaches to consent and communication of results, costs and the potential strain on NHS capacity and resources. Further consultation is required with careful review of pathways and resources before offering AFs in clinical practice."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
Non-coding variants are a rare cause of recessive developmental disorders in trans with coding variants
No full textPURPOSE: Identifying pathogenic non-coding variants is challenging. A single protein-altering variant is often identified in a recessive gene in individuals with developmental disorders (DD), but the prevalence of pathogenic non-coding 'second hits' in trans with these is unknown. METHODS: In 4,073 genetically undiagnosed rare disease trio probands from the 100,000 Genomes project, we identified rare heterozygous protein-altering variants in recessive DD-associated genes. We identified rare non-coding variants on the other haplotype in introns, untranslated regions (UTRs), promoters, and candidate enhancer regions. We clinically evaluated the top candidates for phenotypic fit, and performed functional testing where possible. RESULTS: We identified 3,761 rare heterozygous loss-of-function or ClinVar pathogenic variants in recessive DD-associated genes in 2,430 probands. For 1,366 (36.3%) of these, we identified at least one rare non-coding variant in trans. Bioinformatic filtering and clinical review, revealed seven to be a good clinical fit. After detailed characterisation, we identified likely diagnoses for three probands (in GAA, NPHP3, and PKHD1) and candidate diagnoses in a further three (PAH, LAMA2, IGHMBP2). CONCLUSION: We developed a systematic approach to uncover new diagnoses involving compound heterozygous coding/non-coding variants and conclude that this mechanism is likely to be a rare cause of DDs.Accepted version (6 month embargo), submitted versionRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Mental Imagery to Reduce Alcohol-related harm in patients with alcohol use disorder and alcohol-related liver damaGE: the MIRAGE randomised pilot trial results
No full textOBJECTIVE: The healthcare burden of alcohol-related liver disease (ARLD) is increasing. ARLD and alcohol use disorder (AUD) is best managed by reduction or cessation of alcohol use, but effective treatments are lacking. We tested whether people with ARLD and AUD admitted to hospital could be recruited to and retained in a trial of Functional Imagery Training (FIT), a psychological therapy that uses mental imagery to reduce alcohol craving. We conducted a multicentre randomised pilot trial of treatment as usual (TAU) versus FIT+TAU in people admitted to hospital with ARLD and AUD. DESIGN: Participants were randomised to TAU (a single session of brief intervention) or FIT+TAU (TAU with one hospital-based FIT session then eight telephone sessions over 6 months). Pilot outcomes included recruitment rate and retention at day 180. Secondary outcomes included fidelity of FIT delivery, alcohol use, and severity of alcohol dependence. RESULTS: Fifty-four participants (mean age 49; 63% male) were recruited and randomised, 28 to TAU and 26 to FIT+TAU. The retention rate at day 180 was 43%. FIT was delivered adequately by most alcohol nurses. 50% of intervention participants completed FIT sessions 1 and 2. There were no differences in alcohol use or severity of alcohol dependence between treatment groups at day 180. CONCLUSION: Participants with ARLD and AUD could be recruited to a trial of FIT versus FIT+TAU. However, retention at day 180 was suboptimal. Before conducting a definitive trial of FIT in this patient group, modifications in the intervention and recruitment/retention strategy must be tested. TRIAL REGISTRATION NUMBER: ISRCTN41353774.Published version, accepted version, submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text
Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM
No full textCryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.Published version, accepted version (12 months embrago)RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
Therapeutic modalities of deferiprone in Parkinson's disease: SKY and EMBARK studies
No full textBACKGROUND: Reducing nigrostriatal iron overload reduces neuronal loss in Parkinson's disease (PD) models. OBJECTIVE: Examine the safety and efficacy of deferiprone in reducing motor disability progression in dopaminergic-treated and treatment-naïve patients with early-stage PD. METHODS: Two phase II, multicenter studies, SKY and EMBARK, enrolled patients diagnosed with early PD (<3 years from screening). In SKY, patients on stable dopaminergic therapy were randomized 1:1 to one of four dosage (or placebo-matching) cohorts (300, 600, 900, 1200 mg twice daily [BID]) for 9 months. EMBARK enrolled patients on stable dopaminergic therapy or treatment-naïve patients and received 15 mg/kg BID. For both studies, the primary outcome was the change from baseline to month 9 in motor examination score (Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part III). ClinicalTrials.gov: NCT02728843; ANZCTR: ACTRN12617001578392. RESULTS: Overall, 140 patients were randomized in SKY (28 per cohort). Thirty-six patients enrolled in EMBARK (27 dopaminergic-treated; 9 treatment-naïve). In the SKY study, all doses showed the same worsening as the placebo group, with the exception of the 600 mg dose, which was associated with non-significant reductions in MDS-UPDRS Part III least-squares mean (LSM) between baseline and 9 months (-2-8 points versus placebo). In EMBARK, LSM (SE) changes from baseline in MDS-UPDRS Part III were nonsignificant (-1.6 [1.7]) and significant (8.3 [3.9]) for dopaminergic-treated and treatment-naïve patients, respectively, the latter indicating disease worsening. Adverse events possibly related to deferiprone were reported in 35.7%-88.9% across all deferiprone groups vs. 42.9% for placebo. CONCLUSIONS: SKY and EMBARK studies indicate that deferiprone combined with L-dopa does not provide significant motor function benefit, while the absence of L-dopa treatment worsens symptoms.
Parkinson's disease is an age-related brain condition that can lead to problems with movement, muscle cramps, mental health, and pain. People with Parkinson's disease also struggle with activities of daily living that can reduce their well-being. Researchers have found that some people with Parkinson's disease have high levels of iron in their brain. Currently, we do not know if removing iron from the brain can help people with Parkinson's disease. In this study, we examined if a medicine that removes iron from the brain could improve symptoms of Parkinson's disease. This medicine is called deferiprone. Our study included 176 people with Parkinson's disease. People were then divided into 2 groups. In the first group, people were already being treated for Parkinson's disease and then were given deferiprone for 9 months. We found that a low or high dose of deferiprone did not improve disease symptoms. In the second group, people taking no other medication for their Parkinson's disease were given deferiprone for 9 months. In this group, deferiprone worsened Parkinson's symptoms. There are currently no arguments in favor of using deferiprone in Parkinson's disease. Deferiprone without L-dopa worsens symptoms. Research could potentially evaluate low doses of iron chelator in combination with L-dopa over the long term and in large numbers of people.
engThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).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