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The Potentially Modifiable Risk Factor in Idiopathic Intracranial Hypertension: Body Weight.
No full textPurpose of Review
Idiopathic intracranial hypertension (IIH) prevalence increased in conjunction with rising obesity rates. Here, we highlight the importance of weight management in IIH and introduce glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) as potential treatment strategy for IIH.
Recent Findings
Weight gain is a risk factor for IIH, and weight loss (via any treatment strategy) plays a key role in IIH management. GLP-1 is an incretin secreted by the distal small intestine in response to a meal. GLP-1 RAs have been shown to improve glycaemic control (no hypoglycaemia) and lower body weight in patients with and without type 2 diabetes. The choroid plexus has been found to express GLP-1 receptors, and treatment with a GLP-1 RA significantly reduces CSF secretion in vitro and intracranial pressure (ICP) in rodents.
Summary
New research evaluating the pathophysiology of IIH supports GLP-1 RA as a potential treatment for IIH via weight loss dependent and independent mechanism to directly reduce ICP
Predicting relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis: a Systematic review and meta-analysis.
No full textObjectives
Relapses affect 30-50% of patients with ANCA-associated vasculitis (AAV) over 5 years, necessitating long-term treatment. Although there have been studies looking at predictors of relapse in AAV, this research has yet to translate clinically into guidance on tailored therapy. The aim of this systematic review was to identify and meta-analyse existing risk factors from the literature and produce a model to calculate individualised patient risk of relapse.
Method
A search strategy was developed to include all studies identifying predictors of AAV relapse using multivariate analysis. Individual risk factors were extracted and pooled hazard ratios (HRs) calculated. A model to predict the time to first relapse based on identified risk factors was tested retrospectively using a cohort of patients with AAV.
Results
The review of 2674 abstracts identified 117 papers for full text review, with 16 eligible for inclusion. Pooled HRs were calculated from significant risk factors, including anti-PR3 ANCA positivity [HR 1.69 (95% CI 1.46, 1.94)], cardiovascular involvement [HR 1.78 (95% CI 1.26, 2.53)], creatinine >200 µmol/l (relative to creatinine ≤100) [HR 0.39 (95% CI 0.22, 0.69)] and creatinine 101-200 µmol/l [HR 0.81 (95% CI 0.77, 0.85)]. Using data from 182 AAV patients to validate the model gave a C-statistic of 0.61.
Conclusion
Anti-PR3 ANCA positivity, lower serum creatinine and cardiovascular system involvement are all associated with an increased risk of relapse, and a combination of these risk factors can be used to predict the individualised risk of relapse. In order to produce a clinically useful model to stratify risk, we need to identify more risk factors, with a focus on robust biomarkers
Predicting the immediate impact of national lockdown on neovascular age-related macular degeneration and associated visual morbidity: an INSIGHT Health Data Research Hub for Eye Health report.
No full textOBJECTIVE
Predicting the impact of neovascular age-related macular degeneration (nAMD) service disruption on visual outcomes following national lockdown in the UK to contain SARS-CoV-2.
METHODS AND ANALYSIS
This retrospective cohort study includes deidentified data from 2229 UK patients from the INSIGHT Health Data Research digital hub. We forecasted the number of treatment-naïve nAMD patients requiring anti-vascular endothelial growth factor (anti-VEGF) initiation during UK lockdown (16 March 2020 through 31 July 2020) at Moorfields Eye Hospital (MEH) and University Hospitals Birmingham (UHB). Best-measured visual acuity (VA) changes without anti-VEGF therapy were predicted using post hoc analysis of Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD trial sham-control arm data (n=238).
RESULTS
At our centres, 376 patients were predicted to require anti-VEGF initiation during lockdown (MEH: 325; UHB: 51). Without treatment, mean VA was projected to decline after 12 months. The proportion of eyes in the MEH cohort predicted to maintain the key positive visual outcome of ≥70 ETDRS letters (Snellen equivalent 6/12) fell from 25.5% at baseline to 5.8% at 12 months (UHB: 9.8%-7.8%). Similarly, eyes with VA <25 ETDRS letters (6/96) were predicted to increase from 4.3% to 14.2% at MEH (UHB: 5.9%-7.8%) after 12 months without treatment.
CONCLUSIONS
Here, we demonstrate how combining data from a recently founded national digital health data repository with historical industry-funded clinical trial data can enhance predictive modelling in nAMD. The demonstrated detrimental effects of prolonged treatment delay should incentivise healthcare providers to support nAMD patients accessing care in safe environments.
TRIAL REGISTRATION NUMBER
NCT00056836
Iatrogenic peripheral nerve injury: a guide to management for the orthopaedic limb surgeon.
No full textNerves may be inadvertently injured during trauma surgery due to distorted anatomy, traction applied to a limb, soft tissue retraction, by power tools, instrumentation and from compartment syndrome. Elective orthopaedic surgery has additional risks of joint dislocation for arthroplasty surgery, limb lengthening, thermal injury from cement and direct injury from peripheral nerve blocks.The true incidence is unknown, and many cases are diagnosed as neurapraxia with the expectation of a full and timely recovery without the need for intervention. The incorrect assignation of a neurapraxia diagnosis may delay treatment for a higher grade of injury and in addition fails to recognize that a diagnosis of neurapraxia should be made with caution and a commitment to regular clinical review. Untreated, a neurapraxia can deteriorate and result in axonopathy. The failure to promptly diagnose such a nerve injury and instigate treatment may result in further deterioration and expose the clinician to medicolegal challenge.The focus of this review is to raise awareness of iatrogenic peripheral nerve injuries in orthopaedic limb surgery, the importance of regular clinical examination, the role of investigations, timing and nature of interventions and also to provide a guide to when onward referral to a specialist peripheral nerve injury unit is recommended. Cite this article: 2021;6:607-617. DOI: 10.1302/2058-5241.6.200123
Combining multi-site magnetic resonance imaging with machine learning predicts survival in pediatric brain tumors.
No full textBrain tumors represent the highest cause of mortality in the pediatric oncological population. Diagnosis is commonly performed with magnetic resonance imaging. Survival biomarkers are challenging to identify due to the relatively low numbers of individual tumor types. 69 children with biopsy-confirmed brain tumors were recruited into this study. All participants had perfusion and diffusion weighted imaging performed at diagnosis. Imaging data were processed using conventional methods, and a Bayesian survival analysis performed. Unsupervised and supervised machine learning were performed with the survival features, to determine novel sub-groups related to survival. Sub-group analysis was undertaken to understand differences in imaging features. Survival analysis showed that a combination of diffusion and perfusion imaging were able to determine two novel sub-groups of brain tumors with different survival characteristics (p < 0.01), which were subsequently classified with high accuracy (98%) by a neural network. Analysis of high-grade tumors showed a marked difference in survival (p = 0.029) between the two clusters with high risk and low risk imaging features. This study has developed a novel model of survival for pediatric brain tumors. Tumor perfusion plays a key role in determining survival and should be considered as a high priority for future imaging protocols
Multi-faceted semantic clustering with text-derived phenotypes.
No full textIdentification of ontology concepts in clinical narrative text enables the creation of phenotype profiles that can be associated with clinical entities, such as patients or drugs. Constructing patient phenotype profiles using formal ontologies enables their analysis via semantic similarity, in turn enabling the use of background knowledge in clustering or classification analyses. However, traditional semantic similarity approaches collapse complex relationships between patient phenotypes into a unitary similarity scores for each pair of patients. Moreover, single scores may be based only on matching terms with the greatest information content (IC), ignoring other dimensions of patient similarity. This process necessarily leads to a loss of information in the resulting representation of patient similarity, and is especially apparent when using very large text-derived and highly multi-morbid phenotype profiles. Moreover, it renders finding a biological explanation for similarity very difficult; the black box problem. In this article, we explore the generation of multiple semantic similarity scores for patients based on different facets of their phenotypic manifestation, which we define through different sub-graphs in the Human Phenotype Ontology. We further present a new methodology for deriving sets of qualitative class descriptions for groups of entities described by ontology terms. Leveraging this strategy to obtain meaningful explanations for our semantic clusters alongside other evaluation techniques, we show that semantic clustering with ontology-derived facets enables the representation, and thus identification of, clinically relevant phenotype relationships not easily recoverable using overall clustering alone. In this way, we demonstrate the potential of faceted semantic clustering for gaining a deeper and more nuanced understanding of text-derived patient phenotypes
Dream Content Predicts Motor and Cognitive Decline in Parkinson's Disease.
No full textBackground
Dream content alterations in Parkinson's disease (PD) are associated with motor and cognitive dysfunction cross-sectionally. Although recent studies suggest abnormal dream content in PD might also predict cognitive decline, the relationship between dream content and motor decline in PD remains unknown.
Objective
To investigate whether abnormal dream content in PD predicts both motor and cognitive decline.
Methods
Data were obtained from the Parkinson's Progression Markers Initiative cohort study. Patients were evaluated at baseline and at the 60-month follow-up, with validated clinical scales, including the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Montreal Cognitive Assessment (MoCA), and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III). Patients were dichotomized using RBDSQ item 2, which inquires whether they frequently experience aggression in their dreams. Regression analyses were used to assess whether frequent aggressive dreams at baseline predicted longitudinal changes in MDS-UPDRS III and MoCA scores as well as progression to Hoehn and Yahr stage 3 (H&Y ≥ 3) and cognitive impairment.
Results
Of the patients, 58/224 (25.9%) reported frequent aggressive dreams at baseline. Aggressive dreams predicted a faster increase in MDS-UPDRS III scores (β = 4.64; = 0.007) and a faster decrease in MoCA scores (β = -1.49; = 0.001). Furthermore, they conferred a 6-fold and 2-fold risk for progressing to H&Y ≥ 3 (odds ratio [OR] = 5.82; = 0.005) and cognitive impairment (OR, 2.35; = 0.023) within 60 months. These associations remained robust when adjusting for potential confounders.
Conclusions
This study demonstrates for the first time that frequent aggressive dreams in newly diagnosed PD may independently predict early motor and cognitive decline
Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study.
No full textBACKGROUND
The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes.
METHODS
The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107).
FINDINGS
We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity.
INTERPRETATION
We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care.
FUNDING
UK Research and Innovation and National Institute for Health Research
Cerebrospinal fluid shunting protocol for idiopathic intracranial hypertension for an improved revision rate.
No full textOBJECTIVE
Cerebrospinal fluid (CSF) shunting in idiopathic intracranial hypertension (IIH) is associated with high complication rates, primarily because of the technical challenges that are related to small ventricles and a large body habitus. In this study, the authors report the benefits of a standardized protocol for CSF shunting in patients with IIH as relates to shunt revisions.
METHODS
This was a retrospective study of consecutive patients with IIH who had undergone primary insertion of a CSF shunt between January 2014 and December 2020 at the authors' hospital. In July 2019, they implemented a surgical protocol for shunting in IIH. This protocol recommended IIH shunt insertion by neurosurgeons with expertise in CSF disorders, a frontal ventriculoperitoneal (VP) shunt with an adjustable gravitational valve and integrated intracranial pressure monitoring device, frameless stereotactic insertion of the ventricular catheter, and laparoscopic insertion of the peritoneal catheter. Thirty-day revision rates before and after implementation of the protocol were compared in order to assess the impact of standardizing shunting for IIH on shunt complications.
RESULTS
The 81 patients included in the study were predominantly female (93%), with a mean age of 31 years at primary surgery and mean body mass index (BMI) of 37 kg/m2. Forty-five patients underwent primary surgery prior to implementation of the protocol and 36 patients after. Overall, 12 (15%) of 81 patients needed CSF shunt revision in the first 30 days, 10 before and 2 after introduction of the protocol. This represented a significant reduction in the early revision rate from 22% to 6% after the protocol (p = 0.036). The most common cause of shunt revision for the whole cohort was migration or misplacement of the peritoneal catheter, occurring in 6 of the 12 patients. Patients with a higher BMI were significantly more likely to have a shunt revision within 30 days (p = 0.022).
CONCLUSIONS
The Birmingham standardized IIH shunt protocol resulted in a significant reduction in revisions within 30 days of primary shunt surgery in patients with IIH. The authors recommend standardization for shunting in IIH as a method for improving surgical outcomes. They support the notion of subspecialization for IIH shunts, the use of a frontal VP shunt with sophisticated technology, and laparoscopic insertion of the peritoneal end