PURPOSE: Degenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord dysfunction worldwide, for which surgery is the mainstay of treatment. At present, there is limited literature on the costs associated with the surgical management of DCM, and none from the United Kingdom (UK). This study aimed to evaluate the cost-effectiveness of DCM surgery within the National Health Service, UK. MATERIALS AND METHODS: Incidence of DCM was identified from the Hospital Episode Statistics (HES) database for a single year using five ICD-10 diagnostic codes to represent DCM. Health Resource Group (HRG) data was used to estimate the mean incremental surgery (treatment) costs compared to non-surgical care, and the incremental effect (quality adjusted life year (QALY) gain) was based on data from a previous study. A cost per QALY value of <£30,000/QALY (GBP) was considered acceptable and cost-effective, as per the National Institute for Health and Clinical Excellence (NICE) guidance. A sensitivity analysis was undertaken (±5%, ±10% and ±20%) to account for variance in both the cost of admission and QALY gain. RESULTS: The total number of admissions for DCM in 2018 was 4,218. Mean age was 62 years, with 54% of admissions being of working age (18-65 years). The overall estimated cost of admissions for DCM was £38,871,534 for the year. The mean incremental (per patient) cost of surgical management of DCM was estimated to be £9,216 (ranged £2,358 to £9,304), with a QALY gain of 0.64, giving an estimated cost per QALY value of £14,399/QALY. Varying the QALY gain by ±20%, resulted in cost/QALY figures between £12,000 (+20%) and £17,999 (-20%). CONCLUSIONS: Surgery is estimated to be a cost-effective treatment of DCM amongst the UK population.
INTRODUCTION: Foramen magnum stenosis in achondroplasia carries a risk of sudden death. A proportion of these patients benefit from foramen magnum decompression (FMD). The Achondroplasia Foramen Magnum Score (AFMS) was developed to stratify those most at risk. We hypothesise that this score may be reflected in neurophysiological findings. METHODS: Patients with achondroplasia who had undergone FMD (n=20) were retrospectively grouped into AFMS 2, 3 and 4. Amplitude from tibialis anterior (TA) and the percentage change in somatosensory evoked potential (SSEP) latency after FMD were reported. RESULTS: Baseline motor evoked potential amplitudes for patients with AFMS=4 were significantly lower left (p=0.0017 and p=0.02 for right and left TA, respectively) compared with AFMS grades 2 and 3. Median reduction (% change) in SSEP latency (ms) after surgery was not significantly different in any of the patients. CONCLUSIONS: This short report cross-references AFMS to intraoperative neuromonitoring. Baseline amplitudes were noticeably lower in the most severe AFMS group. This observation supports the notion that AFMS can help risk stratify patients and aid in surgical selection.
OBJECTIVE: Spinal cerebrospinal fluid (CSF) leaks are common, and their management is heterogeneous. For high-flow leaks, numerous studies advocate for primary dural repair and CSF diversion. The LiquoGuard7® allows automated and precise pressure and volume control, and calculation of patient-specific CSF production rate (prCSF), which is hypothesized to be increased in the context of durotomies and CSF leaks. METHODS: This single-centre illustrative case series included patients undergoing complex spinal surgery where: 1) a high flow intra-operative and/or post-operative CSF leak was expected and 2) lumbar CSF drainage was performed using a LiquoGuard7®. CSF diversion was tailored to prCSF for each patient, combined with layered spinal wound closure. RESULTS: Three patients were included, with a variety of pathologies: T7/T8 disc prolapse, T8-T9 meningioma, and T4-T5 metastatic spinal cord compression. The first two patients underwent CSF diversion to prevent post-op CSF leak, whilst the third required this in response to post-op CSF leak. CSF hyperproduction was evident in all cases (mean >/=140ml/hr). With patient-specific CSF diversion regimes, no cases required further intervention for CSF fistulae repair (including for pleural CSF effusion), wound breakdown or infection. CONCLUSIONS: Patient-specific cerebrospinal fluid drainage may be a useful tool in the management of high-flow intra-operative and post-operative CSF leaks during complex spinal surgery. These systems may reduce post-operative CSF leakage from the wound or into adjacent body cavities. Further larger studies are needed to evaluate the comparative benefits and cost-effectiveness of this approach.
Iron oxide nanoparticles (IONPs) surface functionalised with thermo-responsive polymers can encapsulate therapeutic proteins and release them upon heating with an alternating magnetic field above the lower critical solution temperature (LCST). In order to make this delivery system clinically-relevant, we prepared IONPs coated with poly-N-isopropylmethacrylamide (PNIPMAM), a polymer with LCST above human body temperature. The optimal polymer chain length and nanoparticle size to achieve LCST of ca. 45 °C were 19 kDa PNIPMAM and 16 nm IONPs. The PNIPMAM-coated IONPs could encapsulate a range of proteins which were released upon heating above LCST in the presence of a competitor protein or serum. A small amount of encapsulated protein leakage was observed below LCST. The efficiency of protein encapsulation and release was correlated with molecular weight and glycosylation state of the proteins. Magnetic heating resulted in a faster protein release as compared to conventional heating without significant temperature increase of the bulk solution.
Magnetite Nanoparticles , Nanoparticles , Humans , Polymers , Temperature , Magnetics
A composite silicone skin adhesive material was designed to improve its water vapor permeability to offer advantages to wearer comfort compared to existing skin adhesive dressings available (including perforated silicone and hydrocolloid products). The chemical and mechanical properties of this novel dressing were analyzed to show that it has a high creep compliance, offering anisotropic elasticity that is likely to place less stress on the skin. A participant study was carried out in which 31 participants wore a novel silicone skin adhesive (Sil2) and a hydrocolloid competitor and were monitored for physiological response to the dressings. Trans-epidermal water loss (TEWL) was measured pre- and postwear to determine impairment of skin barrier function. Sil2 exhibited a higher vapor permeability than the hydrocolloid dressings during wear. Peel strength measurements and dye counter staining of the removed dressings showed that the hydrocolloid had a higher adhesion to the participants' skin, resulting in a greater removal of proteins from the stratum corneum and a higher pain rating from participants on removal. Once the dressings were removed, TEWL of the participants skin beneath the Sil2 was close to normal in comparison to the hydrocolloid dressings that showed an increase in skin TEWL, indicating that the skin had been highly occluded. Analysis of the skin immediately after removal showed a higher incidence of erythema following application of hydrocolloid dressings (>60%) compared to Sil2, (<30%). In summary, this modified silicone formulation demonstrates superior skin protection properties compared to hydrocolloid dressings and is more suitable for use as a skin adhesive.
Adhesives , Irritants , Humans , Adhesives/adverse effects , Silicones/adverse effects , Bandages, Hydrocolloid , Erythema , Colloids
Spinal Ewing's Sarcoma is a rare tumour predominantly affecting children and adolescents. We describe the case of an 18-year-old male patient who first presented with a primary extradural cervical Ewing's sarcoma tumour, and 5 years later had a recurrence with thoracolumbar and lumbosacral intradural extramedullary Ewing's sarcoma tumours. Both presentations were successfully treated by surgical resection and adjuvant chemo- and radiotherapy, and he remains disease-free at 12 months follow-up. This is the first reported case of seeding of tumour from an extradural primary Ewing's sarcoma to intradural metastases. Total surgical resection of his initial cervical tumour, performed at another centre, was complicated by a dural tear and CSF leak. Thus, we propose that isolated drop metastasis via CSF fistula is the most likely mechanism for tumour spread in this case. Thus, clinicians may wish to counsel patients on the possibility of such spread if a CSF leak is encountered, and potentially increase the frequency of imaging surveillance of the whole spine in this context.
PURPOSE: Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction worldwide. However, the current incidence of DCM is poorly understood. The Hospital Episode Statistics (HES) database contains details of all secondary care admissions across NHS hospitals in England. This study aimed to use HES data to characterise surgical activity for DCM in England. METHODS: The HES database was interrogated for all cases of DCM between 2012 and 2019. DCM cases were identified from 5 ICD-10 codes. Age-stratified values were collected for 'Finished Consultant Episodes' (FCEs), which correspond to a patient's hospital admission under a lead clinician. Data was analysed to explore current annual activity and longitudinal change. RESULTS: 34,903 FCEs with one or more of the five ICD-10 codes were identified, of which 18,733 (53.6%) were of working age (18-64 years). Mean incidence of DCM was 7.44 per 100,000 (SD ± 0.32). Overall incidence of DCM rose from 6.94 per 100,000 in 2012-2013 to 7.54 per 100,000 in 2018-2019. The highest incidence was seen in 2016-2017 (7.94 per 100,000). The median male number of FCEs per year (2919, IQR: 228) was consistently higher than the median female number of FCEs per year (2216, IQR: 326). The rates of both emergency admissions and planned admissions are rising. CONCLUSIONS: The incidence of hospitalisation for DCM in England is rising. Health care policymakers and providers must recognise the increasing burden of DCM and act to address both early diagnoses and access to treatment in future service provision plans.
Spinal Cord Diseases , State Medicine , Adolescent , Adult , Databases, Factual , Female , Hospitalization , Hospitals , Humans , Male , Middle Aged , Spinal Cord Diseases/epidemiology , Spinal Cord Diseases/surgery , Young Adult
PURPOSE: Evaluation of the presentation and outcomes of different surgical treatment approaches for spinal intradural arachnoid cysts (SIAC). METHODS: Cases were identified from electronic records of two major neurosurgical centres in London over the last 10 years (October 2009-October 2019) that have been surgically treated in both institutions. Clinical findings, surgical technique, and recurrence by procedure were statistically analysed. Statistical analysis was performed with STATA 13.1 Software. RESULTS: A total of 42 patients with SIAC were identified for this study with a mean age at the time of surgery of 53.6 years and a male:female ratio of 8:13. There were 31 patients with primary SIACs and 11 with secondary SIACs. The most common presenting symptom was paraesthesia (n = 27). The most common location of the cyst was in the thoracic region (n = 33). Syrinx was present in 26.2% of SIACs (n = 11). Resection was associated with significantly better postoperative pain compared to other surgical techniques (p = 0.01), significantly poorer postoperative urinary function (p = 0.029), and lower rates of sensory recovery in patients who presented preoperatively with sensory deficit (p = 0.041). No significant difference was seen in symptomatic outcomes between patients with primary and secondary SIACs. CONCLUSION: Resection and drainage are both effective methods of managing SIACs. In this observational study, resection was associated with significantly reduced pain postoperatively when compared with drainage, however also with significantly less improvement in postoperative urinary function. Therefore, resection should be the gold standard management option for SIACs, with drainage as an option where resection is unsafe, and drainage should also be considered in patients presenting with urinary dysfunction.
Arachnoid Cysts , Syringomyelia , Arachnoid Cysts/diagnostic imaging , Arachnoid Cysts/surgery , Female , Humans , Male , Pain/surgery , Paresthesia , Spinal Cord Diseases , Treatment Outcome
OBJECTIVES: To assess the reporting of study design and characteristics in multi-level degenerative cervical myelopathy (DCM) treated by posterior surgical approaches, and perform a comparison of clinical and radiographic outcomes between different approaches. METHODS: A literature search was performed in Embase and MEDLINE between 1995-2019 using a sensitive search string combination. Studies were selected by predefined selection criteria: Full text articles in English, with >10 patients (prospective) or >50 patients (retrospective), reporting outcomes of multi-level DCM treated by posterior surgical approach. RESULTS: A total of 75 studies involving 19,510 patients, conducted worldwide, were identified. Laminoplasty was described in 56 studies (75%), followed by laminectomy with (36%) and without fusion (16%). The majority of studies were conducted in Asia (84%), in the period of 2016-2019 (51%), of which laminoplasty was studied predominantly. Twelve (16%) prospective studies and 63 (84%) retrospective studies were identified. The vast majority of studies were conducted in a single centre (95%) with clear inclusion/exclusion criteria and explicit cause of DCM. Eleven studies (15%) included patients with ossification of the posterior longitudinal ligament exclusively with cohorts of 57 to 252. The clinical and radiographic outcomes were reported with heterogeneity when comparing laminoplasty, laminectomy with and without fusion. CONCLUSIONS: Heterogeneity in the reporting of study and sample characteristics exists, as well as in clinical and radiographic outcomes, with a paucity of studies with a higher level of evidence. Future studies are needed to elucidate the clinical effectiveness of posterior surgical treatments.
Rapid point of care tests for bacterial infection diagnosis are of great importance to reduce the misuse of antibiotics and burden of antimicrobial resistance. Here, we have successfully combined a new class of non-biological binder molecules with electrochemical impedance spectroscopy (EIS)-based sensor detection for direct, label-free detection of Gram-positive bacteria making use of the specific coil-to-globule conformation change of the vancomycin-modified highly branched polymers immobilized on the surface of gold screen-printed electrodes upon binding to Gram-positive bacteria. Staphylococcus carnosus was detected after just 20 min incubation of the sample solution with the polymer-functionalized electrodes. The polymer conformation change was quantified with two simple 1 min EIS tests before and after incubation with the sample. Tests revealed a concentration dependent signal change within an OD600 range of Staphylococcus carnosus from 0.002 to 0.1 and a clear discrimination between Gram-positive Staphylococcus carnosus and Gram-negative Escherichia coli bacteria. This exhibits a clear advancement in terms of simplified test complexity compared to existing bacteria detection tests. In addition, the polymer-functionalized electrodes showed good storage and operational stability.
Biosensing Techniques , Vancomycin , Bacteria , Dielectric Spectroscopy , Electrochemical Techniques , Electrodes , Gold , Polymers , Staphylococcus
INTRODUCTION: Chiari 1 malformation (CM1) is a structural abnormality of the hindbrain characterised by the descent of the cerebellar tonsils through the foramen magnum. The management of patients with CM1 remains contentious since there are currently no UK or international guidelines for clinicians. We therefore propose a collaborative, prospective, multicentre study on the investigation, management and outcome of CM1 in the UK: the UK Chiari 1 Study (UKC1S). Our primary objective is to determine the health-related quality of life (HRQoL) in patients with a new diagnosis of CM1 managed either conservatively or surgically at 12 months of follow-up. We also aim to: (A) determine HRQoL 12 months following surgery; (B) measure complications 12 months following surgery; (C) determine the natural history of patients with CM1 treated conservatively without surgery; (D) determine the radiological correlates of presenting symptoms, signs and outcomes; and (E) determine the scope and variation within UK practice in referral patterns, patient pathways, investigations and surgical decisions. METHODS AND ANALYSIS: The UKC1S will be a prospective, multicentre and observational study that will follow the British Neurosurgical Trainee Research Collaborative model of collaborative research. Patients will be recruited after attending their first neurosurgical outpatient clinic appointment. Follow-up data will be collected from all patients at 12 months from baseline regardless of whether they are treated surgically or not. A further 12-month postoperative follow-up timepoint will be added for patients treated with decompressive surgery. The study is expected to last three years. ETHICS AND DISSEMINATION: The UKC1S received a favourable ethical opinion from the East Midlands Leicester South Research Ethics Committee (REC reference: 20/EM/0053; IRAS 269739) and the Health Research Authority. The results of the study will be published in peer-reviewed medical journals, presented at scientific conferences, shared with collaborating sites and shared with participant patients if they so wish.
Arnold-Chiari Malformation , Quality of Life , Arnold-Chiari Malformation/surgery , Humans , Multicenter Studies as Topic , Observational Studies as Topic , Prospective Studies , Radiography , United Kingdom
BACKGROUND: The optimal management of craniopharyngiomas remains controversial. OBJECTIVES: To examine temporal trends in the management of craniopharyngioma with a focus on endocrine outcomes. METHODS: This was a cross-sectional, multicentre study. Patients treated between 1951 and 2015 were identified and divided into four quartiles. Demographics, presentation, treatment and outcomes were collected. RESULTS: In total, 142 patients with childhood-onset craniopharyngioma (48/142; 34%) and adult-onset disease (94/142; 66%) were included. The median follow-up was 15 years (IQR 5-23 years). Across quartiles, there was a significant trend towards using transsphenoidal surgery (P < .0001). The overall use of radiotherapy was not different among the four quartiles (P = .33). At the latest clinical review, the incidence of GH, ACTH, gonadotrophin deficiencies and anterior panhypopituitarism fell significantly across the duration of the study. Anterior panhypopituitarism was not affected by treatment modality (surgery vs surgery and radiotherapy) (P = .23). There was no difference in the incidence of high BMI (≥25 kg/m2 ) among the four quartiles (P = .14). BMI was higher in patients who treated with surgery and radiotherapy than those treated with surgery only (P = .006). Tumour regrowth occurred in 51 patients (51/142; 36%) with no difference in regrowth among quartiles over the time course of the study (P = .15). CONCLUSION: We demonstrate a significant reduction in panhypopituitarism in craniopharyngioma patients over time, most likely because of a trend towards more transsphenoidal surgery. However, long-term endocrine sequelae remain common and lifelong follow-up is required.
Craniopharyngioma , Hypopituitarism , Pituitary Neoplasms , Adult , Child , Craniopharyngioma/radiotherapy , Craniopharyngioma/surgery , Cross-Sectional Studies , Follow-Up Studies , Humans , Hypopituitarism/etiology , Pituitary Neoplasms/surgery , Retrospective Studies
Highly branched poly(N-isopropylacrylamide) (HB-PNIPAM), functionalized with vancomycin at the chain ends, acted as a bacterial adhesive and was incorporated into polyurethane foams to form semi-interpenetrating networks. PNIPAM was labeled with a solvatochromic dye, Nile red. It was found that the thermal response of the polymer was dependent on the architecture, and temperature-dependent color changes were observed within the foam. The foams had open pore structures, and the presence of HB-PNIPAM substantially reduced the shrinkage of the foam as the temperature was increased up to 20 °C. The foams were selectively adhesive for Staphylococcus aureus (Gram-positive bacteria) compared to Pseudomonas aeruginosa (Gram-negative bacteria), and the presence of S. aureus was indicated by increased fluorescence intensity (590-800 nm).
Acrylic Resins/pharmacology , Anti-Bacterial Agents/pharmacology , Biocompatible Materials/pharmacology , Polyurethanes/pharmacology , Vancomycin/pharmacology , Acrylic Resins/chemistry , Anti-Bacterial Agents/chemistry , Biocompatible Materials/chemistry , Materials Testing , Microbial Sensitivity Tests , Molecular Structure , Particle Size , Polyurethanes/chemistry , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Vancomycin/chemistry
Battered Child Syndrome/epidemiology , Coronavirus Infections/epidemiology , Craniocerebral Trauma/epidemiology , Intracranial Hemorrhages/epidemiology , Neurosurgery , Pneumonia, Viral/epidemiology , Referral and Consultation/statistics & numerical data , Spinal Injuries/epidemiology , Accidental Falls/statistics & numerical data , Betacoronavirus , COVID-19 , Central Nervous System Infections/epidemiology , Central Nervous System Neoplasms/epidemiology , Child , Child, Preschool , Cohort Studies , Emergencies , Emergency Service, Hospital , Female , Humans , Hydrocephalus/epidemiology , Infant , Infant, Newborn , Male , Pandemics , Prospective Studies , SARS-CoV-2 , Skull Fractures/epidemiology , United Kingdom/epidemiology
BACKGROUND: The standard treatment for symptomatic Chiari malformation (CM) I is foramen magnum decompression (FMD) to facilitate cerebral spinal fluid flow through the foramen magnum, improve intracranial compliance, and alleviate symptoms (commonly headache). This procedure has a variable success rate, with a significant proportion of patients having persistent symptoms after surgery. OBJECTIVE: To investigate intracranial pressure (ICP) hydrodynamics in symptomatic surgery-naïve patients with CM I and symptomatic patients who have had prior FMD. METHODS: We undertook a retrospective, observational cohort study, extracting data from our departmental ICP database. Patients with untreated ("Virgin") Chiari malformations (VCM), patients with previous "failed" FMD (ie, with persistent classical Chiari symptoms) (fFMD) and a normal control group, all with existing continuous ICP monitoring date were included. Median ICP (mICP) and median pulse amplitude (mPA) were compared between the groups. RESULTS: A total of 33 CM patients (22 VCM and 11 fFMD) and 42 normal controls were included for analysis. mICP did not differ significantly between the normal control, VCM, and fFMD groups. mPA in the VCM and fFMD groups was significantly higher than the control group (P < .01 and P < .05, respectively). CONCLUSION: In this cohort, patients with persistent symptoms after FMD have persistently impaired intracranial compliance, similar to patients who have not undergone surgery at all when compared with a control group. The reasons for this are not clear, and further research is required to establish the causation and optimum management for failed FMD.
Arnold-Chiari Malformation/surgery , Decompression, Surgical/methods , Foramen Magnum/surgery , Intracranial Pressure/physiology , Treatment Failure , Adult , Arnold-Chiari Malformation/diagnostic imaging , Cohort Studies , Decompression, Surgical/trends , Female , Foramen Magnum/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/trends , Male , Middle Aged , Retrospective Studies
PURPOSE: There is anecdotal evidence that many patients who undergo reduction mammoplasty (RM) procedures, to relieve symptoms of large breasts, also report improvement in existing back pain. Given how important back pain is as a healthcare burden, the literature which explores the relationship between RM and back pain is sparse. Thus, we aimed to appraise whether such a correlation exists, through systematic review and meta-analysis. METHOD: Adhering to PRISMA methodology, we used the OVID engine to search the MEDLINE and Embase databases with predefined search terms and inclusion criteria. MeSH terms were not exploded. Statistical analysis was performed using Review Manager 5.3, employing a Mantell-Haenszel method and a fixed-effect model suitable for dichotomous data. RESULTS: The review yielded 13 articles after exclusions, eight of which were suitable for quantitative analysis. The results of the analysis suggested an improvement in back pain following RM across all studies (OR 40.37 [8.09, 201.53] 95% CI, n = 1008). Heterogeneity was high (τ2 = 5.14, χ2 = 230.37, df = 7 (p < 0.00001) i2 = 97%). CONCLUSIONS: Although cursory, the evidence gleaned suggests that RM reduces the prevalence of back pain in patients with large breasts. Furthermore, we highlight the scarcity of studies investigating whether RM is at the clinical threshold of efficacy in treating back pain. Although the evidence is insufficient for recommending RM as a management option aimed at treating back pain, this review does identify the need for prospective data looking at back pain metrics as a specific outcome measure before and after reduction mammoplasty.
Back Pain , Low Back Pain , Mammaplasty , Back Pain/epidemiology , Back Pain/surgery , Female , Humans , Hypertrophy , Low Back Pain/surgery , Prospective Studies
Cervical disc arthroplasty is a treatment option for symptomatic cervical disc disease. There is a paucity of literature on long-term safety outcomes, durability, and device-related failure rates. The M6-C artificial cervical disc is a device with titanium alloy endplates and a complex polymeric centerpiece. To date, trials have exhibited acceptable safety profiles.This case series describes the presentation, management, and pathological findings of a delayed prevertebral periprosthetic mass anterior to the M6-C disc. Four patients at 3 different institutions underwent cervical disc replacement with the M6-C disc. Two to seven years postoperatively, they presented with dysphagia secondary to a compressive mass anterior to the disc. Case notes were reviewed to collect data on symptoms, management, and outcomes. The patients were systemically well and presented with progressive dysphagia. They had imaging findings of a mass anterior to the disc. They underwent a decompressive procedure, with 2 patients undergoing device removal and fusion. In 2 cases, a soft-tissue mass was seen intraoperatively, with frank pus. In 3 cases, Propionibacterium acnes was identified and antibiotic treatment given. Histopathology demonstrated mixed inflammatory infiltrates with foreign body-type granulomas. Postoperatively, the dysphagia resolved.The development of delayed dysphagia in a patient with an M6-C disc should prompt investigation to identify a mass lesion. To the authors' knowledge, this is the first report of delayed infection, or suspected delayed-type hypersensitivity reaction, following M6-C disc implantation. It is important for this to be added to the device safety concerns. Further prospective studies are needed to establish the incidence and the long-term safety and failure rates of the M6-C disc.
BACKGROUND: Elective intraparenchymal intracranial pressure (ICP) monitoring is useful for the diagnosis and treatment of hydrocephalus and cerebrospinal fluid (CSF) disorders. This retrospective study analyzes median ICP and pulse amplitude (PA) recordings in neurosurgically naïve patients undergoing elective ICP monitoring for suspected CSF disorders. METHODS: Retrospective review of prospectively collated database of neurosurgically naïve patients undergoing elective ICP monitoring for suspected hydrocephalus and CSF disorders. Following extraction of the median ICP and PA values (separated into all, day and night time recordings), principal component analysis (PCA) was performed to identify the principal factors determining the spread of the data. Exploratory comparisons and correlations of ICP and PA values were explored, including by post hoc diagnostic groupings and age. RESULTS: A total of 198 patients were identified in six distinct diagnostic groups (n = 21-47 in each). The PCA suggested that there were two main factors accounting for the spread in the data, with 61.4% of the variance determined largely by the PA and 33.0% by the ICP recordings. Exploratory comparisons of PA and ICP between the diagnostic groups showed significant differences between the groups. Specifically, significant differences were observed in PA between a group managed conservatively and the Chiari/syrinx, IIH, and NPH/LOVA groups and in the ICP between the conservatively managed group and high-pressure, IIH, and low-pressure groups. Correlations between ICP and PA revealed some interesting trends in the different diagnostic groups and correlations between ICP, PA, and age revealed a decreasing ICP and increasing PA with age. CONCLUSIONS: This study provides insights into hydrodynamic disturbances in different diagnostic groups of patients with CSF hydrodynamic disorders. It highlights the utility of analyzing both median PA and ICP recordings, stratified into day and night time recordings.
Hydrocephalus/diagnosis , Intracranial Pressure/physiology , Monitoring, Physiologic/methods , Adolescent , Adult , Aged , Aged, 80 and over , Databases, Factual , Female , Heart Rate/physiology , Humans , Hydrocephalus/physiopathology , Male , Middle Aged , Retrospective Studies , Young Adult
Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN)-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees) or anti-LF (in AVP vaccinees) antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens.
Adaptive Immunity/immunology , Anthrax Vaccines/immunology , Anthrax/immunology , Skin Diseases, Bacterial/immunology , Adult , Antibodies, Bacterial/immunology , Antigens, Bacterial/immunology , Bacterial Toxins/immunology , Female , Humans , Immune Sera/immunology , Immunoglobulin G/immunology , Interferon-gamma/immunology , Male , Middle Aged , Vaccination/methods
Anthrax is a serious, potentially fatal disease that can present in four distinct clinical patterns depending on the route of infection (cutaneous, gastrointestinal, pneumonic, or injectional); effective strategies for prophylaxis and therapy are therefore required. This review addresses the complex mechanisms of pathogenesis employed by the bacterium and describes how, as understanding of these has developed over many years, so too have current strategies for vaccination and therapy. It covers the clinical and veterinary use of live attenuated strains of anthrax and the subsequent identification of protein sub-units for incorporation into vaccines, as well as combinations of protein sub-units with spore or other components. It also addresses the application of these vaccines for conventional prophylactic use, as well as post-exposure use in conjunction with antibiotics. It describes the licensed acellular vaccines AVA and AVP and discusses the prospects for a next generation of recombinant sub-unit vaccines for anthrax, balancing the regulatory requirement and current drive for highly defined vaccines, against the risk of losing the "danger" signals required to induce protective immunity in the vaccinee. It considers novel approaches to reduce time to immunity by means of combining, for example, dendritic cell vaccination with conventional approaches and considers current opportunities for the immunotherapy of anthrax.
