Approaches to risk ratio estimation in a regression discontinuity design: Application to the prescription of statins for cholesterol reduction in UK primary care.

In recent years regression discontinuity designs have been used increasingly for the estimation of treatment effects in observational medical data where a rule-based decision to apply treatment is taken using a continuous assignment variable. Most regression discontinuity design applications have focused on effect estimation where the outcome of interest is continuous, with scenarios with binary outcomes receiving less attention, despite their ubiquity in medical studies. In this work, we develop an approach to estimation of the risk ratio in a fuzzy regression discontinuity design (where treatment is not always strictly applied according to the decision rule), derived using common regression discontinuity design assumptions.

Contribution of White Matter Fiber Bundle Damage to Language Change After Surgery for Temporal Lobe Epilepsy.

Background And Objectives: In medically refractory temporal lobe epilepsy (TLE), 30%-50% of patients experience substantial language decline after resection in the language-dominant hemisphere. In this study, we investigated the contribution of white matter fiber bundle damage to language change at 3 and 12 months after surgery.

Methods: We studied 127 patients who underwent TLE surgery from 2010 to 2019.

Hippocampal resection in temporal lobe epilepsy: Do we need to resect the tail?

Introduction: Anteromesial temporal lobe resection is the most common surgical technique used to treat drug-resistant mesial temporal lobe epilepsy, particularly when secondary to hippocampal sclerosis. Structural and functional imaging data suggest the importance of sparing the posterior hippocampus for minimising language and memory deficits. Recent work has challenged the view that maximal posterior hippocampal resection improves seizure outcome.

Long-term seizure, psychiatric and socioeconomic outcomes after frontal lobe epilepsy surgery.

Objective: Resective surgery for selected individuals with frontal lobe epilepsy can be effective, although multimodal outcomes are less established than in temporal lobe epilepsy. We describe long-term seizure remission and relapse patterns, psychiatric comorbidity, and socioeconomic outcomes following frontal lobe epilepsy surgery.

Methods: We reviewed individual data on frontal lobe epilepsy procedures at our center between 1990 and 2020.

Zibotentan in systemic sclerosis-associated chronic kidney disease: a phase II randomised placebo-controlled trial.

Background: We report results from a phase II randomised placebo-controlled trial assessing zibotentan, a highly selective endothelin receptor antagonist (ERA), in chronic kidney disease (CKD) secondary to systemic sclerosis (SSc).

Methods: This trial included three sub-studies: ZEBRA 1-a randomised placebo-controlled, double-blind trial of zibotentan in SSc patients with CKD2 or CKD3 (and glomerular filtration rate (GFR) >45 ml/min) over 26 weeks; ZEBRA 2A-a 26-week placebo-controlled, single-blind trial of zibotentan in scleroderma renal crisis patients not requiring dialysis; and ZEBRA 2B-an open label pharmacokinetic study of zibotentan in patients on haemodialysis.

Results: Sixteen patients were screened for ZEBRA 1.

Cost of pre-surgical evaluation for epilepsy surgery: A single-center experience.

Objective: To estimate the cost and time taken to evaluate adults with drug-resistant focal epilepsy for potentially curative surgery.

Methods: We reviewed data on 100 consecutive individuals at a tertiary referral center evaluated for epilepsy surgery in 2017. The time elapsed between referral and either surgery or a definitive decision not to progress was measured.

Resective, Ablative and Radiosurgical Interventions for Drug Resistant Mesial Temporal Lobe Epilepsy: A Systematic Review and Meta-Analysis of Outcomes.

One-third of individuals with focal epilepsy do not achieve seizure freedom despite best medical therapy. Mesial temporal lobe epilepsy (MTLE) is the most common form of drug resistant focal epilepsy. Surgery may lead to long-term seizure remission if the epileptogenic zone can be defined and safely removed or disconnected.

Seizure outcomes in people with drug-resistant focal epilepsy evaluated for surgery but do not proceed.

Objective: To ascertain seizure outcomes in people with drug-resistant focal epilepsy considered for epilepsy surgery but who did not proceed.

Methods: We identified people discussed at a weekly presurgical epilepsy multi-disciplinary (MDT) meeting from January 2015 to December 2019 and in whom a decision not to proceed to surgery was made. Seizure outcomes were obtained from individuals, primary care physicians and attending neurologists at a minimum of 12 months following the not to proceed decision.

Reasons for not having epilepsy surgery.

Objective: This study was undertaken to determine reasons for adults with drug-resistant focal epilepsy who undergo presurgical evaluation not proceeding with surgery, and to identify predictors of this course.

Methods: We retrospectively analyzed data on 617 consecutive individuals evaluated for epilepsy surgery at a tertiary referral center between January 2015 and December 2019. We compared the characteristics of those in whom a decision not to proceed with surgical treatment was made with those who underwent definitive surgery in the same period.

Community Occupational Therapy for people with dementia and family carers (COTiD-UK) versus treatment as usual (Valuing Active Life in Dementia [VALID]) study: A single-blind, randomised controlled trial.

Background: We aimed to estimate the clinical effectiveness of Community Occupational Therapy for people with dementia and family carers-UK version (Community Occupational Therapy in Dementia-UK version [COTiD-UK]) relative to treatment as usual (TAU). We hypothesised that COTiD-UK would improve the ability of people with dementia to perform activities of daily living (ADL), and family carers' sense of competence, compared with TAU.

Methods And Findings: The study design was a multicentre, 2-arm, parallel-group, assessor-masked, individually randomised controlled trial (RCT) with internal pilot.

Automated computation and analysis of accuracy metrics in stereoencephalography.

Background: Implantation accuracy of electrodes during neurosurgical interventions is necessary to ensure safety and efficacy. Typically, metrics are computed by visual inspection which is tedious, prone to inter-/intra-observer variation, and difficult to replicate across sites.

New Method: We propose an automated approach for computing implantation metrics and investigate potential sources of error.

Exploratory Randomized Double-Blind Placebo-Controlled Trial of Botulinum Therapy on Grasp Release After Stroke (PrOMBiS).

. OnabotulinumtoxinA injections improve upper-limb spasticity after stroke, but their effect on arm function remains uncertain. .

Multicenter validation of automated trajectories for selective laser amygdalohippocampectomy.

Objective: Laser interstitial thermal therapy (LITT) is a novel minimally invasive alternative to open mesial temporal resection in drug-resistant mesial temporal lobe epilepsy (MTLE). The safety and efficacy of the procedure are dependent on the preplanned trajectory and the extent of the planned ablation achieved. Ablation of the mesial hippocampal head has been suggested to be an independent predictor of seizure freedom, whereas sparing of collateral structures is thought to result in improved neuropsychological outcomes.

Automated fiber tract reconstruction for surgery planning: Extensive validation in language-related white matter tracts.

Diffusion MRI and tractography hold great potential for surgery planning, especially to preserve eloquent white matter during resections. However, fiber tract reconstruction requires an expert with detailed understanding of neuroanatomy. Several automated approaches have been proposed, using different strategies to reconstruct the white matter tracts in a supervised fashion.

Correlated multistate models for multiple processes: an application to renal disease progression in systemic .

Bidirectional changes over time in the estimated glomerular filtration rate and in urine protein content are of interest for the treatment and management of patients with . Although these processes may be modelled by separate multistate models, the processes are likely to be correlated within patients. Motivated by the application, we develop a new multistate modelling framework where subject-specific random effects are introduced to account for the correlations both between the processes and within patients over time.

Automatic segmentation of stereoelectroencephalography (SEEG) electrodes post-implantation considering bending.

Purpose: The accurate and automatic localisation of SEEG electrodes is crucial for determining the location of epileptic seizure onset. We propose an algorithm for the automatic segmentation of electrode bolts and contacts that accounts for electrode bending in relation to regional brain anatomy.

Methods: Co-registered post-implantation CT, pre-implantation MRI, and brain parcellation images are used to create regions of interest to automatically segment bolts and contacts.

Computer-assisted planning for the insertion of stereoelectroencephalography electrodes for the investigation of drug-resistant focal epilepsy: an external validation study.

Objective: One-third of cases of focal epilepsy are drug refractory, and surgery might provide a cure. Seizure-free outcome after surgery depends on the correct identification and resection of the epileptogenic zone. In patients with no visible abnormality on MRI, or in cases in which presurgical evaluation yields discordant data, invasive stereoelectroencephalography (SEEG) recordings might be necessary.

Protocol for a 1-year prospective, longitudinal cohort study of patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy: the BARI-LIFESTYLE observational study.

Introduction: Roux-en-Y gastric bypass and sleeve gastrectomy are the two most common bariatric surgery performed in the UK that result in comparable weight loss and remission of obesity-associated comorbidities. However, there is a paucity of studies examining the impact of these procedures on body composition, physical activity levels, sedentary behaviour, physical function and strength, dietary intake, health-related quality of life and costs.

Methods And Analysis: The BARI-LIFESTYLE observational study is a 1-year prospective, longitudinal cohort study within a real-world routine clinical care setting aiming to recruit 100 patients with severe obesity undergoing either primary Roux-en-Y gastric bypass or sleeve gastrectomy from two bariatric centres in London, UK.

Automated trajectory planning for laser interstitial thermal therapy in mesial temporal lobe epilepsy.

Objective: Surgical resection of the mesial temporal structures brings seizure remission in 65% of individuals with drug-resistant mesial temporal lobe epilepsy (MTLE). Laser interstitial thermal therapy (LiTT) is a novel therapy that may provide a minimally invasive means of ablating the mesial temporal structures with similar outcomes, while minimizing damage to the neocortex. Systematic trajectory planning helps ensure safety and optimal seizure freedom through adequate ablation of the amygdalohippocampal complex (AHC).

Assessing cognitive dysfunction in Parkinson's disease: An online tool to detect visuo-perceptual deficits.

Background: People with Parkinson's disease (PD) who develop visuo-perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuo-perceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo-perceptual deficits in PD.

Improving patient safety during introduction of novel medical devices through cumulative summation analysis.

OBJECTIVE The aim of this study was to implement cumulative summation (CUSUM) analysis as an early-warning detection and quality assurance system for preclinical testing of the iSYS1 novel robotic trajectory guidance system. METHODS Anatomically accurate 3D-printed skull phantoms were created for 3 patients who underwent implantation of 21 stereoelectroencephalography electrodes by surgeons using the current standard of care (frameless technique). Implantation schema were recreated using the iSYS1 system, and paired accuracy measures were compared with the previous frameless implantations.

Auras and the risk of seizures with impaired consciousness following epilepsy surgery: implications for driving.

Objective: To calculate the chance of a seizure in the next year (COSY) for seizures with impaired awareness in those experiencing auras only, those with no seizures and those with continuing seizures. Epilepsy surgery is an effective treatment for refractory focal epilepsy. Driving is an important factor affecting quality of life.

Sample size calculations based on a difference in medians for positively skewed outcomes in health care studies.

Background: In healthcare research, outcomes with skewed probability distributions are common. Sample size calculations for such outcomes are typically based on estimates on a transformed scale (e.g.