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1.
N Engl J Med ; 388(24): 2219-2229, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37092792

ABSTRACT

BACKGROUND: Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear. METHODS: We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy. An inclusion criterion was a bone flap with an anteroposterior diameter of 11 cm or more. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOSE) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 12 months. Secondary outcomes included the GOSE rating at 6 months and quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). RESULTS: A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The median diameter of the bone flap was 13 cm (interquartile range, 12 to 14) in both groups. The common odds ratio for the differences across GOSE ratings at 12 months was 0.85 (95% confidence interval, 0.60 to 1.18; P = 0.32). Results were similar at 6 months. At 12 months, death had occurred in 30.2% of the patients in the craniotomy group and in 32.2% of those in the craniectomy group; a vegetative state occurred in 2.3% and 2.8%, respectively, and a lower or upper good recovery occurred in 25.6% and 19.9%. EQ-5D-5L scores were similar in the two groups at 12 months. Additional cranial surgery within 2 weeks after randomization was performed in 14.6% of the craniotomy group and in 6.9% of the craniectomy group. Wound complications occurred in 3.9% of the craniotomy group and in 12.2% of the craniectomy group. CONCLUSIONS: Among patients with traumatic acute subdural hematoma who underwent craniotomy or decompressive craniectomy, disability and quality-of-life outcomes were similar with the two approaches. Additional surgery was performed in a higher proportion of the craniotomy group, but more wound complications occurred in the craniectomy group. (Funded by the National Institute for Health and Care Research; RESCUE-ASDH ISRCTN Registry number, ISRCTN87370545.).


Subject(s)
Craniotomy , Decompressive Craniectomy , Hematoma, Subdural, Acute , Humans , Craniotomy/adverse effects , Craniotomy/methods , Decompressive Craniectomy/adverse effects , Decompressive Craniectomy/methods , Glasgow Outcome Scale , Hematoma, Subdural, Acute/surgery , Quality of Life , Retrospective Studies , Skull/surgery , Treatment Outcome , Surgical Flaps/surgery
2.
N Engl J Med ; 383(27): 2616-2627, 2020 12 31.
Article in English | MEDLINE | ID: mdl-33326713

ABSTRACT

BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.).


Subject(s)
Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use , Hematoma, Subdural, Chronic/drug therapy , Administration, Oral , Aged , Combined Modality Therapy , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Disabled Persons , Female , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Hematoma, Subdural, Chronic/complications , Hematoma, Subdural, Chronic/mortality , Hematoma, Subdural, Chronic/surgery , Humans , Intention to Treat Analysis , Male , Middle Aged , Reoperation/statistics & numerical data , Severity of Illness Index , Treatment Outcome
3.
Br J Cancer ; 124(4): 697-709, 2021 02.
Article in English | MEDLINE | ID: mdl-33144698

ABSTRACT

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)-an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles-to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.


Subject(s)
Brain Neoplasms/therapy , Electric Stimulation Therapy/methods , Glioblastoma/therapy , Animals , Brain Neoplasms/pathology , Clinical Trials, Phase III as Topic , Glioblastoma/pathology , Humans , Randomized Controlled Trials as Topic
4.
Cytokine ; 123: 154778, 2019 11.
Article in English | MEDLINE | ID: mdl-31323526

ABSTRACT

INTRODUCTION: There is some evidence to suggest that a systemic and central nervous system (CNS) inflammatory response occurs following aneurysmal subarachnoid haemorrhage (aSAH) which may be related to the pathophysiology of early brain injury and delayed ischaemic neurological deficit (DIND). The aim of this study was to measure inflammatory mediator levels in plasma and cerebrospinal fluid (CSF) in the days following aSAH and to determine their association with aSAH, DIND and clinical outcome. MATERIAL AND METHODS: Plasma and CSF samples were obtained prospectively from patients with aSAH on days 1-3, 5, 7 and 9 and profiled for interleukin (IL)-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-15, IL-17, IL-18, macrophage chemotactic protein (MCP)-1, vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF)-α. Plasma and CSF samples from non-aSAH patients undergoing spinal anaesthesia were used as controls. RESULTS: The CSF levels of all cytokines investigated except for IL-1α were significantly higher in aSAH compared to controls in the first seven days of ictus. CSF levels of IL-1α (p = 0.014), IL-18 (p = 0.016), IL-6 (p = 0.0006) and IL-8 (p = 0.006) showed significant increases in the days following aSAH. Conversely IL-17 demonstrated a decrease. In particular, IL-4 was higher in the CSF of patients who had DIND at all time-points (p = 0.032). Plasma IL-6 and IL-8 levels were higher, and IL-1α levels lower, than controls at most time-points. All mediators demonstrated persistent elevation in the CSF compared to plasma apart from IL-1α and IL-18 which followed the opposite trend. Day 3 plasma IL-6 levels predicted poor outcome at six months (Exp(B) 1.12 1.03-1.22, P = 0.012), although this association was lost in the second analysis incorporating Fisher grade, WFNS grade and age. CONCLUSION: The post aSAH inflammatory response peaks on days 5-7 post ictus and remains largely compartmentalised within the CNS. IL-4 may have a particular association with DIND although its precise role in the pathophysiology of the disorder remains unclear. IL-6 predicted poor outcome but not independently of clinical grade, suggesting that it may be a surrogate marker of early brain injury.


Subject(s)
Brain Injuries , Cytokines , Subarachnoid Hemorrhage , Aged , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Brain Injuries/blood , Brain Injuries/cerebrospinal fluid , Cytokines/blood , Cytokines/cerebrospinal fluid , Female , Humans , Inflammation/blood , Inflammation/cerebrospinal fluid , Male , Middle Aged , Subarachnoid Hemorrhage/blood , Subarachnoid Hemorrhage/cerebrospinal fluid
6.
Br J Neurosurg ; 28(3): 408-10, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24564244

ABSTRACT

Klippel-Feil syndrome (KPS) is a congenital spinal deformity characterised by the presence of at least one fused cervical segment. We report an unusual case of a fracture through fused cervical segment in a patient with KPS, who presented with quadriparesis and progressed on to develop respiratory failure and quadriplegia and who had a successful outcome following surgery. To the best of our knowledge, fracture through fused cervical segments in a Klippel-Feil patient has not been reported previously and this case report extends the spectrum of injuries seen in patients with KPS.


Subject(s)
Cervical Vertebrae/injuries , Cervical Vertebrae/surgery , Klippel-Feil Syndrome/complications , Spinal Fractures/complications , Spinal Fractures/surgery , Spinal Fusion , Fracture Fixation, Intramedullary , Humans , Male , Quadriplegia/etiology , Treatment Outcome , Young Adult
7.
BMJ Open ; 14(6): e085084, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38885989

ABSTRACT

OBJECTIVE: To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH). DESIGN: Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial. SETTING: UK secondary care. PARTICIPANTS: 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122). INTERVENTIONS: Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery). MAIN OUTCOME MEASURES: In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists. RESULTS: In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be -£5520 (95% CI -£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be -£4536 (95% CI -£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE. CONCLUSIONS: In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant). ETHICS: Ethical approval for the trial was obtained from the North West-Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076). TRIAL REGISTRATION NUMBER: ISRCTN87370545.


Subject(s)
Cost-Benefit Analysis , Craniotomy , Decompressive Craniectomy , Hematoma, Subdural, Acute , Quality-Adjusted Life Years , Adult , Aged , Female , Humans , Male , Middle Aged , Craniotomy/economics , Craniotomy/methods , Decompressive Craniectomy/economics , Glasgow Outcome Scale , Hematoma, Subdural, Acute/surgery , Hematoma, Subdural, Acute/economics , Treatment Outcome , United Kingdom
8.
Health Technol Assess ; 28(12): 1-122, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38512045

ABSTRACT

Background: Chronic subdural haematoma is a collection of 'old blood' and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases. Objective: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma. Design: This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation. Setting: Neurosurgical units in the UK. Participants: Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging. Interventions: Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care. Main outcome measures: The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0-3) or an unfavourable (score of 4-6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Results: A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (-8.2%, 95% confidence interval -13.3% to -3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be -£97.19. Conclusions: This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group. Future work and limitations: A total of 94% of individuals underwent surgery, meaning that this trial does not fully define the role of dexamethasone in conservatively managed haematomas, which is a potential area for future study. Trial registration: This trial is registered as ISRCTN80782810. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information.


Chronic subdural haematoma is one of the most common conditions managed in adult neurosurgery and mainly affects older people. It is an 'old' collection of blood and blood breakdown products found on the surface of the brain. Surgery to drain the liquid collection is effective, with most patients improving. Given that inflammation is involved in the disease process, a commonly used steroid, dexamethasone, has been used alongside surgery or instead of surgery since the 1970s. However, there is no consensus or high-quality studies confirming the effectiveness of dexamethasone for the treatment of chronic subdural haematoma. This study was designed to determine the effectiveness of adding dexamethasone to the normal treatment for patients with a symptomatic chronic subdural haematoma. The benefit of adding dexamethasone was measured using a disability score called the Modified Rankin Scale, which can be divided into favourable and unfavourable outcomes. This was assessed at 6 months after entry into the study. In total, 748 adults with a symptomatic chronic subdural haematoma treated in neurosurgical units in the UK participated. Each participant had an equal chance of receiving either dexamethasone or a placebo because they were assigned randomly. Neither the patients nor the investigators knew who received dexamethasone and who received placebo. Most patients in both groups had an operation to drain the haematoma and experienced significant functional improvement at 6 months compared with their initial admission to hospital. However, patients who received dexamethasone had a lower chance than patients who received placebo of favourable recovery at 6 months. Specifically, 84% of patients who received dexamethasone had recovered well at 6 months, compared with 90% of patients who received placebo. There were more complications in the group that received dexamethasone. This trial demonstrates that adding dexamethasone to standard treatment reduced the chance of a favourable outcome compared with standard treatment alone. Therefore, this study does not support the use of dexamethasone in treating patients with a symptomatic chronic subdural haematoma.


Subject(s)
Hematoma, Subdural, Chronic , Adult , Humans , Aged , Hematoma, Subdural, Chronic/drug therapy , Hospitalization , Cost-Benefit Analysis , Double-Blind Method , Dexamethasone/therapeutic use
9.
Acta Neurochir Suppl ; 115: 13-6, 2013.
Article in English | MEDLINE | ID: mdl-22890636

ABSTRACT

Patients recovered from subarachnoid hemorrhage can be assessed for neuropsychological dysfunction using postal questionnaires. We assessed 214 patients using various tests of memory, mood and strategic thinking. Patients in good outcome categories (modified Rankin Scale [mRS] 0-1) nevertheless exhibited mood disorder (28%), memory deficit and executive dysfunction (20%). Return to work (49%) was most influenced by previous employment status, Rankin scale and mood.


Subject(s)
Cognition Disorders/diagnosis , Memory Disorders/diagnosis , Mood Disorders/diagnosis , Subarachnoid Hemorrhage/psychology , Cognition Disorders/etiology , Cohort Studies , Female , Glasgow Coma Scale , Humans , Male , Memory Disorders/etiology , Mood Disorders/etiology , Neuropsychological Tests , Retrospective Studies , Self Report , Subarachnoid Hemorrhage/complications , Surveys and Questionnaires , Time Factors
10.
Health Technol Assess ; 27(21): 1-228, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37929307

ABSTRACT

Background: Posterior cervical foraminotomy and anterior cervical discectomy are routinely used operations to treat cervical brachialgia, although definitive evidence supporting superiority of either is lacking. Objective: The primary objective was to investigate whether or not posterior cervical foraminotomy is superior to anterior cervical discectomy in improving clinical outcome. Design: This was a Phase III, unblinded, prospective, United Kingdom multicentre, parallel-group, individually randomised controlled superiority trial comparing posterior cervical foraminotomy with anterior cervical discectomy. A rapid qualitative study was conducted during the close-down phase, involving remote semistructured interviews with trial participants and health-care professionals. Setting: National Health Service trusts. Participants: Patients with symptomatic unilateral cervical brachialgia for at least 6 weeks. Interventions: Participants were randomised to receive posterior cervical foraminotomy or anterior cervical discectomy. Allocation was not blinded to participants, medical staff or trial staff. Health-care use from providing the initial surgical intervention to hospital discharge was measured and valued using national cost data. Main outcome measures: The primary outcome measure was clinical outcome, as measured by patient-reported Neck Disability Index score 52 weeks post operation. Secondary outcome measures included complications, reoperations and restricted American Spinal Injury Association score over 6 weeks post operation, and patient-reported Eating Assessment Tool-10 items, Glasgow-Edinburgh Throat Scale, Voice Handicap Index-10 items, PainDETECT and Numerical Rating Scales for neck and upper-limb pain over 52 weeks post operation. Results: The target recruitment was 252 participants. Owing to slow accrual, the trial closed after randomising 23 participants from 11 hospitals. The qualitative substudy found that there was support and enthusiasm for the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial and randomised clinical trials in this area. However, clinical equipoise appears to have been an issue for sites and individual surgeons. Randomisation on the day of surgery and processes for screening and approaching participants were also crucial factors in some centres. The median Neck Disability Index scores at baseline (pre surgery) and at 52 weeks was 44.0 (interquartile range 36.0-62.0 weeks) and 25.3 weeks (interquartile range 20.0-42.0 weeks), respectively, in the posterior cervical foraminotomy group (n = 14), and 35.6 weeks (interquartile range 34.0-44.0 weeks) and 45.0 weeks (interquartile range 20.0-57.0 weeks), respectively, in the anterior cervical discectomy group (n = 9). Scores appeared to reduce (i.e. improve) in the posterior cervical foraminotomy group, but not in the anterior cervical discectomy group. The median Eating Assessment Tool-10 items score for swallowing was higher (worse) after anterior cervical discectomy (13.5) than after posterior cervical foraminotomy (0) on day 1, but not at other time points, whereas the median Glasgow-Edinburgh Throat Scale score for globus was higher (worse) after anterior cervical discectomy (15, 7, 6, 6, 2, 2.5) than after posterior cervical foraminotomy (3, 0, 0, 0.5, 0, 0) at all postoperative time points. Five postoperative complications occurred within 6 weeks of surgery, all after anterior cervical discectomy. Neck pain was more severe on day 1 following posterior cervical foraminotomy (Numerical Rating Scale - Neck Pain score 8.5) than at the same time point after anterior cervical discectomy (Numerical Rating Scale - Neck Pain score 7.0). The median health-care costs of providing initial surgical intervention were £2610 for posterior cervical foraminotomy and £4411 for anterior cervical discectomy. Conclusions: The data suggest that posterior cervical foraminotomy is associated with better outcomes, fewer complications and lower costs, but the trial recruited slowly and closed early. Consequently, the trial is underpowered and definitive conclusions cannot be drawn. Recruitment was impaired by lack of individual equipoise and by concern about randomising on the day of surgery. A large prospective multicentre trial comparing anterior cervical discectomy and posterior cervical foraminotomy in the treatment of cervical brachialgia is still required. Trial registration: This trial is registered as ISRCTN10133661. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 21. See the NIHR Journals Library website for further project information.


Cervical brachialgia is pain that starts in the neck and passes down into the arm. Although most people with cervical brachialgia recover quickly, in some patients pain persists, and in 15% of patients pain is so severe that they are unable to work. In the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial, we investigated two neck surgeries used to treat this problem: posterior cervical foraminotomy (surgery from the back of the neck) and anterior cervical discectomy (surgery from the front of the neck). This trial aimed to find out if one of them is better than the other at relieving pain and more cost-effective for the National Health Service. We assessed patients' quality of life 1 year after their surgery and how their pain changed over the course of the year. We also measured the number of complications patients had in the first 6 weeks after their operation. Recruitment was slow and so the trial was stopped early, after only 23 patients from 11 hospitals had been randomly allocated to the two surgery groups. We had planned to recruit 252 participants to the trial; the number of participants we were able to recruit in practice was too small to enable us to determine which surgery is better at relieving pain. To find out why the trial had struggled to recruit, we asked hospital staff and participants about their experiences. We found that hospital staff sometimes struggled to organise everything needed to randomise patients on the day of surgery. Some staff also found it difficult to randomise patients as they had an opinion on which surgery they thought the patient should receive. The data collected in the trial will still be useful to help design future research. Finding out which surgery is better at relieving pain remains important, and the data we have collected will support answering this question in future.


Subject(s)
Foraminotomy , Humans , State Medicine , Neck Pain , Prospective Studies , Diskectomy , Cost-Benefit Analysis , Quality of Life
11.
Stroke ; 43(3): 677-82, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22282887

ABSTRACT

BACKGROUND AND PURPOSE: A single-center prospective randomized controlled trial has been conducted to determine if lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage reduces the prevalence of delayed ischemic neurological deficit and improves clinical outcome. METHODS: Patients with World Federation of Neurological Surgeons Grade 1 to 3 aneurysmal subarachnoid hemorrhage and modified Fisher Grades 2, 3, 4, and 3+4 were randomized to either the study group of standard therapy plus insertion of a lumbar drain or the control group of standard therapy alone. The primary outcome measure was the prevalence of delayed ischemic neurological deficit. RESULTS: Two hundred ten patients with aneurysmal subarachnoid hemorrhage (166 female, 44 male; median age, 54 years; interquartile range, 45-62 years) were recruited into the control (n=105) and study (n=105) groups of the trial. World Federation of Neurological Surgeons grade was: 1 (n=139), 2 (n=60), and 3 (n=11); Fisher grade was: 2 (n=87), 3 (n=85), and 4 (n=38). The prevalence of delayed ischemic neurological deficit was 35.2% and 21.0% in the control and study groups, respectively (P=0.021). The prevalence of a modified Rankin Scale score of 4, 5, or 6 at Day 10 and 6 months, respectively, was 62.5% and 18.6% in the control group and 44.8% and 19.8% in the study group (P=0.009 and 0.83, respectively). CONCLUSIONS: Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage has been shown to reduce the prevalence of delayed ischemic neurological deficit and improve early clinical outcome but failed to improve outcome at 6 months after aneurysmal subarachnoid hemorrhage. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00842049.


Subject(s)
Drainage/methods , Nervous System Diseases/prevention & control , Subarachnoid Hemorrhage/cerebrospinal fluid , Subarachnoid Hemorrhage/therapy , Adult , Aged , Cohort Studies , Double-Blind Method , Female , Follow-Up Studies , Humans , Intention to Treat Analysis , Lumbosacral Region , Male , Middle Aged , Nervous System Diseases/etiology , Prospective Studies , Subarachnoid Hemorrhage/complications , Treatment Outcome
12.
Br J Neurosurg ; 26(4): 510-3, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22686127

ABSTRACT

INTRODUCTION: There are many indications for cranioplasty with an increasing incidence partly attributable to an increase in decompressive craniectomy following trauma and stroke. The aim of this study was to compare the survival of acrylic and titanium cranioplasties used in our department. MATERIALS AND METHODS: Retrospective cohort study of 126 patients who underwent cranioplasty between 1997 and 2007. A comparison was made between those with acrylic (n = 61) and titanium (n = 65) cranioplasties. There was no significant difference in age and length of time between craniectomy and cranioplasty between the two groups. The indications for titanium cranioplasty tended to be classified as 'high risk' indications including trauma and stroke. A higher rate of pre-existing infection was noted in the acrylic group. Mean follow-up was 97.2 and 34 months for acrylic and titanium cranioplasties respectively. RESULTS: Mean survival (95% confidence intervals) was 135 months (134-153) and 92 months (82-102) for acrylic and cranioplasty respectively. Out of 13 failures, only two were associated with pre-existing infection. Overall cumulative survival was better for acrylic cranioplasty although this difference did not reach statistical significance. DISCUSSION: Although survival of acrylic cranioplasty appears to be better than titanium plates, there is no statistical significance. Acrylic has the advantage of being able to be applied at the time of surgery without any planning and does not cause artefact on future imaging. Titanium cranioplasty is strong, light-weight and inert and can be fashioned in the pre-operative setting.


Subject(s)
Bone Cements/therapeutic use , Craniotomy/adverse effects , Polymethyl Methacrylate/therapeutic use , Skull/surgery , Titanium/therapeutic use , Adult , Humans , Kaplan-Meier Estimate , Middle Aged , Retrospective Studies , Surgical Wound Infection/etiology , Treatment Failure
13.
Childs Nerv Syst ; 27(9): 1493-8, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21842349

ABSTRACT

Arteriovenous malformations (AVM) constitute a clinically significant form of vascular malformations in children. We present three cases of paediatric AVMs that demonstrated unusual features of high flow and significant shunting of blood without a clearly demonstrable nidus. Venous malformations were associated with the lesions. A discussion of the concepts underlying AVM physiology and how these case reports contradict these is included.


Subject(s)
Intracranial Arteriovenous Malformations/diagnostic imaging , Intracranial Arteriovenous Malformations/therapy , Adolescent , Cerebral Angiography , Child , Embolization, Therapeutic , Female , Humans , Male , Treatment Outcome
14.
Acta Neurochir Suppl ; 110(Pt 2): 203-7, 2011.
Article in English | MEDLINE | ID: mdl-21125472

ABSTRACT

The traditional axiom that vasospasm induced reduction of blood flow leads to poor tissue oxygenation and ischaemic cellular injury culminating in delayed neurological deficits has been challenged and the efficacy of triple H therapy in reversal of the above is debated. In this study we assess cerebral physiology before and during onset of DIND and with application of triple H therapy with real time neuro-monitoring tools. Patients with Fisher grade 3/4/3 + 4/rebleed were consented. Probes for measuring rCBF, pTiO2, and Microdialysis parameters - glucose, glycerol, lactate, and pyruvate were inserted at time of coiling/clipping. Subsequent monitoring was done in HDU/ITU setting. Return of parameters to baseline was regarded as effective triple H therapy. Study is ongoing and the current paper presents our experience with first five patients. The results suggest safety and feasibility of multimodal monitoring in clinical setting to establish an understanding of relationship between clinical symptoms, brain perfusion, oxygenation, and metabolism in real time to test and guide therapy in future.


Subject(s)
Blood Pressure/physiology , Blood Volume/physiology , Cerebrovascular Circulation/physiology , Hemodilution , Nervous System Diseases/therapy , Humans , Hypoxia-Ischemia, Brain/complications , Lactic Acid/blood , Microdialysis/methods , Monitoring, Physiologic/methods , Nervous System Diseases/complications , Nervous System Diseases/etiology , Prospective Studies , Pyruvic Acid/blood
15.
Br J Neurosurg ; 25(2): 310-2, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21545330

ABSTRACT

We report a case of cervical spine, tracheal and oesophageal trauma from a go-karting injury caused by the patient's scarf catching in the vehicle's wheel. We discuss the significance of the pre-hospital and operative management of this potentially life-threatening injury by a multi-specialty surgical team. The importance of health and safety issues in recreational sports is highlighted in view of the increasing incidence of cervical spine trauma over past two decades.


Subject(s)
Cervical Vertebrae/injuries , Esophagus/injuries , Quadriplegia/etiology , Trachea/injuries , Accidents , Cervical Vertebrae/surgery , Esophagus/surgery , Female , Heart Arrest/etiology , Humans , Syndrome , Tracheostomy/methods , Young Adult
16.
World Neurosurg ; 146: e1255-e1261, 2021 02.
Article in English | MEDLINE | ID: mdl-33276170

ABSTRACT

BACKGROUND: The current study is an external validation of 4 scoring models proposed in the literature for predicting ventriculoperitoneal shunt insertion after aneurysmal subarachnoid hemorrhage (aSAH) using retrospective patient data from Sheffield Teaching Hospital (STH). METHODS: Data were collected on various demographics, and patients were individually scored using the 4 scoring models. Models were compared with each other using receiver-operator characteristic curves. The best model had the highest area under the curve. RESULTS: A total of 301 aSAH patients were referred to the neurosurgery department in STH between 1 January 2014 and 31 December 2017. Scoring model 4 also had the largest area under the curve of 0.853 (P < 0.001), and scoring model 3 had the lowest area under the curve of 0.654 (P = 0.036). CONCLUSIONS: Scoring model 4 was found to be the best scoring model out of the 4 scoring models externally validated to predict shunt dependency after an aSAH in STH patients. Scoring model 4 is less applicable in modern practice due to a higher proportion of coiling and use of the Hunt and Hess scale grade. A new scoring model is needed to predict shunt insertion in modern practice.


Subject(s)
Aneurysm, Ruptured/surgery , Hydrocephalus/surgery , Intracranial Aneurysm/surgery , Subarachnoid Hemorrhage/surgery , Ventriculoperitoneal Shunt/statistics & numerical data , Adult , Age Factors , Aged , Aged, 80 and over , Aneurysm, Ruptured/complications , Drainage , Female , Humans , Hydrocephalus/etiology , Intracranial Aneurysm/complications , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Risk Assessment , Rupture, Spontaneous , Severity of Illness Index , Subarachnoid Hemorrhage/complications , Ventriculostomy/statistics & numerical data , Young Adult
17.
World Neurosurg ; 133: e646-e652, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31568913

ABSTRACT

OBJECTIVES: With an aging population and advances in neuroanesthesia and critical care, an increasing subgroup of elderly patients have been undergoing neurosurgery. Of particular relevance is the cohort aged >80 years. The aim of the present study was to investigate the 30-day mortality and survival in this cohort after emergency and elective neurosurgery. METHODS: We performed a retrospective cohort study of all patients aged ≥70 years who had undergone a neurosurgical procedure from 2015 to 2017. The patient demographic data were identified, and independent predictors were found using logistic regression analysis. RESULTS: A total of 796 patients were included, of whom 622 were aged <80 years (group A) and 174 were aged >80 years (group B). Overall survival was 86.3% in group A and 79.9% in group B. The 30-day mortality between the elective (0.8%) and emergency (10.1%) patients was significantly different statistically (P < 0.001). Of the patients in groups A and B, 84.7% and 68.9% were discharged back to their usual residence, respectively. Logistic regression found emergency surgery to be an independent predictor of mortality. CONCLUSIONS: The current model for accepting elderly patients has been associated with good overall outcomes. The elderly should not be refused neurosurgery on the basis of their age alone. However, we applied fairly strict criteria, especially for those with subarachnoid hemorrhage, which should be factored into our results.


Subject(s)
Neurosurgical Procedures/mortality , Aged , Aged, 80 and over , Cohort Studies , Female , Frail Elderly , Humans , Male , Retrospective Studies
18.
Cancers (Basel) ; 11(3)2019 Mar 25.
Article in English | MEDLINE | ID: mdl-30934632

ABSTRACT

In this perspective, we congratulate the international efforts to highlight critical challenges in brain tumor research through a recent Consensus Statement. We also illustrate the importance of developing more accurate and clinically relevant early translational in vitro brain tumor models-a perspective given limited emphasis in the Consensus Statement, despite in vitro models being widely used to prioritize candidate therapeutic strategies prior to in vivo studies and subsequent clinical trials. We argue that successful translation of effective novel treatments into the clinic will require investment into the development of more predictive early pre-clinical models. It is in the interest of researchers, clinicians, and ultimately, patients that the most promising therapeutic candidates are identified and translated toward use in the clinic. Highlighting the value of early pre-clinical brain tumor models and debating how such models can be improved is of the utmost importance to the neuro-oncology research community and cancer research more broadly.

19.
Sci Rep ; 9(1): 5885, 2019 04 10.
Article in English | MEDLINE | ID: mdl-30971773

ABSTRACT

The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.


Subject(s)
Dexamethasone/therapeutic use , Hematoma, Subdural, Chronic/drug therapy , Dexamethasone/adverse effects , Double-Blind Method , Drug Administration Schedule , Hematoma, Subdural, Chronic/pathology , Humans , Pilot Projects , Placebo Effect , Randomized Controlled Trials as Topic , Treatment Outcome
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