An economic evaluation of eptinezumab for the preventive treatment of migraine in the UK, with consideration for natural history and work productivity.

BACKGROUND: Migraine is a highly prevalent neurological disease with a substantial societal burden due to lost productivity. From a societal perspective, we assessed the cost-effectiveness of eptinezumab for the preventive treatment of migraine. METHODS: An individual patient simulation of discrete competing events was developed to evaluate eptinezumab cost-effectiveness compared to best supportive care for adults in the United Kingdom with ≥ 4 migraine days per month and prior failure of ≥ 3 preventive migraine treatments. Individuals with sampled baseline characteristics were created to represent this population, which comprised dedicated episodic and chronic migraine subpopulations. Clinical efficacy, utility, and work productivity inputs were based on results from the DELIVER randomised controlled trial (NCT04418765). Timing of natural history events and treatment holidays-informed by the literature-were simulated to unmask any natural improvement of the disease unrelated to treatment. The primary outcomes were monthly migraine days, migraine-associated costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, and net monetary benefit, each evaluated over a 5-year time horizon from 2020. Secondary analyses explored a lifetime horizon and an alternative treatment stopping rule. RESULTS: Treatment with eptinezumab resulted in an average of 0.231 QALYs gained at a saving of £4,894 over 5 years, making eptinezumab dominant over best supportive care (i.e., better health outcomes and less costly). This result was confirmed by the probabilistic analysis and all alternative assumption scenarios under the same societal perspective. Univariate testing of inputs showed net monetary benefit was most sensitive to the number of days of productivity loss, and monthly salary. CONCLUSIONS: This economic evaluation shows that from a societal perspective, eptinezumab is a cost-effective treatment in patients with ≥ 4 migraine days per month and for whom ≥ 3 other preventive migraine treatments have failed. TRIAL REGISTRATION: N/A.

Learning from past in the aircraft maintenance industry: An empirical evaluation in the safety management framework.

The growth of commercial air transport arguably translates into more aging passenger aircraft queuing up for major maintenance, modifications, and/or freighter conversion with the aircraft maintenance industry. In the competitive business environment, this increased maintenance demand possesses the potential to stress the industry and make safety vulnerable. In the aircraft maintenance industry, several aircraft accidents and incidents have resulted from organizational failure to learn from the past. To address this chronic problem, this study aims to (a) establish a learning process model for the aircraft maintenance industry, (b) identify the factors that influence learning, and (c) determine the effect of identified factors on learning from the past. A review of scholarly articles and regulatory publications enabled the development of learning from the past process model and a data collection tool, followed by structural equation modeling to quantify the relationship among influencing factors. The study was conducted in the Indian aircraft maintenance environment and is based on the perspective of the front-line maintenance staff. The study found that safety communication is the decisive stage for learning from the past. Contextualization of the safety information and evaluating the lessons learned during safety communication strongly impact learning from the past, for which existing regulatory provisions are vulnerable. The findings of this study are meant to assist State regulators and management of the aircraft maintenance industry; nevertheless, safety managers and practitioners in other ultra-safe, high-risk sectors may also apply the results in compliance with the respective regulatory guidelines.

Detection of Epileptic Seizure Using Accelerometer Time Series Data and Hidden Markov Model.

Epilepsy is one of the most prevalent neurological diseases globally, which causes seizures in the patient. As per a survey done worldwide, it is found that approximately 70 million people are living with epilepsy (~1% of the total population of the world). Effective detection of these seizures requires specialized approaches such as video and electroencephalography monitoring, which are expensive and are mainly available at specialized hospitals and institutes. Hence, there is a need to develop simpler and affordable systems that can be made available to health care centers and patients for accurate detection of epileptic seizures. A wireless remote monitoring system based on a wrist-worn accelerometer is an optimum choice for the same. Sophisticated algorithms need to be developed for effectively detecting seizure events from this accelerometer data with minimal false alarms. This paper presents a Hidden Markov Model (HMM) based probabilistic approach applied to the reduced-dimension feature vector representation of time-series accelerometer data to detect epileptic seizures. The results obtained from the HMM were compared with three commonly used machine learning models viz. support vector machine (SVM), logistic regression, and random forest. The proposed approach was able to detect 95.7% of seizures with a low false alarm rate of 14.8% with a run time of just under 24 seconds.

Efficacy of erenumab and factors predicting response after 3 months in treatment resistant chronic migraine: a clinical service evaluation.

BACKGROUND: Calcitonin gene-related peptide (CGRP) inhibitors have been developed as options for treatment of chronic and episodic migraine. We present our experience of the use of erenumab in a tertiary headache centre. METHODS: This was a prospective clinical audit of all patients commenced on erenumab following a locally agreed pathway and criteria over a consecutive period. Patients received monthly erenumab 140 mg for 3 months. Data were collected prospectively at baseline and 3 months follow up. RESULTS: One hundred three patients were commenced on erenumab during the study period. Patients had tried a median of 7 previous prophylactics, including onabotulinum toxin A in 94%. At 3 months there was a reduction in median total (28 to 20, 29% reduction, p < 0.0001) and severe (15 to 5, 67% reduction, p < 0.0001) headache days. 39.8% of patients achieved at least a 30% reduction in total headache days; 61.8% of patients achieved at least a 50% reduction in severe headache days. Meeting either of these thresholds was considered a positive response, 68% of patients achieved this. Presence of daily headache pattern was negatively associated with response, (56% response vs. 90% without daily headache, p = 0.0003). There was no association between age, gender, presence of medication overuse or number of previously tried prophylactic treatments and response to erenumab. 43% of patients reported at least one adverse effect, most commonly constipation (26%); treatment was discontinued in 3 patients due to adverse effects. CONCLUSIONS: Erenumab was an effective treatment for chronic migraine in this treatment resistant population over 3 months of follow up. Presence of daily headache predicted poorer response but there was still a significant positive response rate in this group.

Chronic Migraine: An Update on Diagnosis and Management.

BACKGROUND: Chronic migraine is an under-recognized and under-treated disorder. A greater understanding of the pathophysiology of migraine and transformation to chronic migraine has led to the first targeted treatments for chronic migraine. In this review, we review current approaches to the diagnosis and management of chronic migraine and discuss recent and emerging novel therapies. OBJECTIVE: The aim of this study was to provide an update on the diagnosis and management of chronic migraine. METHODS AND MATERIAL: The PubMed database was searched for relevant articles published on or before October 2020. RESULTS AND CONCLUSIONS: Chronic migraine is an under-recognized and under-treated disorder. Prompt diagnosis and appropriate management can lead to a significant improvement in the quality of life with subsequent socioeconomic benefits.

Substantia nigra micro-haemorrhage causing ipsilateral unilateral Parkinsonism and abnormal dopamine transporter scan uptake.

Parkinsonism is a commonly seen movement disorder syndrome with neurodegenerative and non-neurodegenerative causes. Presynaptic dopamine transporter (DaT) single-photon emission computed tomography (SPECT) imaging is the most commonly used imaging technique in clinical practice to differentiate degenerative Parkinson's disease (PD) and PD plus syndromes from other causes such as essential tremor and drug-induced parkinsonism. This can help identify the patients who would benefit from medical therapy due to underlying pre-synaptic dopaminergic deficits. We report a case of unilateral parkinsonism caused by ipsilateral substantia nigra micro-haemorrhage resulting in disruption of the nigrostriatal pathway. This is an unusual case of a 55-year-old male patient who presented with unilateral Parkinsonism a decade after significant head trauma where MRI plays a critical and complementary role in diagnosing complete interruption of the nigrostriatal pathway due to cerebral micro-haemorrhage. The case also beautifully demonstrates the anatomy of the nigrostriatal pathway where a small lesion in the substantia nigra caused complete loss of radioligand uptake in the ipsilateral corpus striatum. Physicians should be aware of the importance of structural imaging in atypical movement disorder cases and, in particular, the routine use of susceptibility-weighted sequences (SWI).

Differential efficacy of non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A meta-analysis.

BACKGROUND: Two randomized, double-blind, sham-controlled trials (ACT1, ACT2) evaluated non-invasive vagus nerve stimulation (nVNS) as acute treatment for cluster headache. We analyzed pooled ACT1/ACT2 data to increase statistical power and gain insight into the differential efficacy of nVNS in episodic and chronic cluster headache. METHODS: Data extracted from ACT1 and ACT2 were pooled using a fixed-effects model. Main outcome measures were the primary endpoints of each study. This was the proportion of participants whose first treated attack improved from moderate (2), severe (3), or very severe (4) pain intensity to mild (1) or nil (0) for ACT1 and the proportion of treated attacks whose pain intensity improved from 2-4 to 0 for ACT2. RESULTS: The pooled population included 225 participants (episodic: n = 112; chronic: n = 113) from ACT1 (n = 133) and ACT2 (n = 92) in the nVNS (n = 108) and sham (n = 117) groups. Interaction was shown between treatment group and cluster headache subtype (p < 0.05). nVNS was superior to sham in episodic but not chronic cluster headache (both endpoints p < 0.01). Only four patients discontinued the studies due to adverse events. CONCLUSIONS: nVNS is a well-tolerated and effective acute treatment for episodic cluster headache. TRIAL REGISTRATION: The studies were registered at clinicaltrials.gov (ACT1: NCT01792817; ACT2: NCT01958125).

Reversible cerebral vasoconstriction syndrome secondary to caffeine withdrawal.

We describe a 39-year-old man who developed thunderclap headaches during a hospital admission for accidental superficial burns. His magnetic resonance brain imaging was normal expect for diffuse segmental vasoconstriction. Prior to admission, he was consuming excessive amounts of caffeine which was restarted and slowly tapered and stopped over weeks. Repeat magnetic resonance angiogram showed resolution of segmental vasoconstriction. The implications of prescribed and non-prescribed drugs on cerebral vasculature have been discussed.

Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A randomized, double-blind, sham-controlled ACT2 study.

Background Clinical observations and results from recent studies support the use of non-invasive vagus nerve stimulation (nVNS) for treating cluster headache (CH) attacks. This study compared nVNS with a sham device for acute treatment in patients with episodic or chronic CH (eCH, cCH). Methods After completing a 1-week run-in period, subjects were randomly assigned (1:1) to receive nVNS or sham therapy during a 2-week double-blind period. The primary efficacy endpoint was the proportion of all treated attacks that achieved pain-free status within 15 minutes after treatment initiation, without rescue treatment. Results The Full Analysis Set comprised 48 nVNS-treated (14 eCH, 34 cCH) and 44 sham-treated (13 eCH, 31 cCH) subjects. For the primary endpoint, nVNS (14%) and sham (12%) treatments were not significantly different for the total cohort. In the eCH subgroup, nVNS (48%) was superior to sham (6%; p < 0.01). No significant differences between nVNS (5%) and sham (13%) were seen in the cCH subgroup. Conclusions Combing both eCH and cCH patients, nVNS was no different to sham. For the treatment of CH attacks, nVNS was superior to sham therapy in eCH but not in cCH. These results confirm and extend previous findings regarding the efficacy, safety, and tolerability of nVNS for the acute treatment of eCH.

Study of Inter-relationship of Depression, Seizure Frequency and Quality of Life of People with Epilepsy in India.

Epilepsy is a chronic neurological disorder that can have profound physical, social and psychological consequences. We aimed to assess the clinical predictors of quality of life of people with epilepsy. We recruited 31 patients suffering from epilepsy in this cross-sectional study. Their clinical profile was recorded. Quality Of Life in Epilepsy (QOLIE-31) was used to assess quality of life of our patients. Depression was screened by Neurological Disorders Depression Inventory in Epilepsy (NDDI-E). Among all the clinical variables, only seizure frequency significantly correlated with seizure worry (P=0.002), emotional well-being (P=0.026) and social functions (P=0.013) subscales of QOLIE-31. NDDIE score showed a significant negative correlation with all the subscales of QOLIE-31 except medication effects (P=0.993). A significant positive correlation was also noted between seizure frequency and NDDI-E score (r=0.417, P=0.020). Seizure frequency and depression are the most important predictors of quality of life in epilepsy patients. The management of patients with epilepsy should not only be aimed at just preventing seizures but the treating clinicians should also be cognizant about depression which itself can significantly affect the quality of life of patients.

Possible Correlation of Transfusion Transmitted Diseases with Rh type and ABO Blood Group System.

BACKGROUND: Screening of blood is mandatory for transfusion transmitted diseases and is routinely done in the blood banks. As blood is the major source transmission of hepatitis B, hepatitis C, human immunodeficiency virus & many other diseases the hazards can be minimised by effective donor selection and screening. AIM: To find out the correlation between the transfusion transmitted diseases and blood groups and the seroprevalence of HIV, HBV, HCV & syphilis among the apparently healthy human blood donors. Study, Setting & Design: This retrospective study was conducted at the blood bank of a tertiary health care teaching centre for a period of four years. MATERIAL AND METHODS: All voluntary and replacement donors reporting to the blood bank were screened for HIV-1 & 2, HBsAg, HCV and Syphilis. Anti-HIV -1 & 2, HBsAg & anti - HCV was tested using the appropriate Enzyme-linked immunosorbent assay (ELISA) technique using micro-elisa kit supplied by J.Mitra & Co.Ltd. The seropositive samples were again tested on ELISA kits of RFCL &/or BIORAD for further confirmation & ruling out any false positive or false negative results. The rapid plasma reagain (RPR) test was used for estimation of syphilis infection. STATISTICAL ANALYSIS: The data entry was carried out using Microsoft office excel worksheet and was analysed by percentage and comparison. RESULTS: Total of 6000 donors were screened which included voluntary and replacement donors. Seroprevalence of HIV (0.1833 %), HCV (1.28%), HBsAg (1.5833 %) and syphilis (0.4333 %) was detected. In the study done it was also noted - that the NEGATIVE blood groups were more prone to TTIs. Blood group A negative was more prone to TTIs with HIV, HBsAg and VDRL while blood group B negative was more affected by HCV. CONCLUSION: Seroprevalence of these infections shows that routine screening is a must for blood and blood product safe transfusion. Do negative blood groups predispose to TTIs? A finding which makes us think….

New daily persistent headache.

New daily persistent headache (NDPH) is a chronic headache developing in a person who does not have a past history of headaches. The headache begins acutely and reaches its peak within 3 days. It is important to exclude secondary causes, particularly headaches due to alterations in cerebrospinal fluid (CSF) pressure and volume. A significant proportion of NDPH sufferers may have intractable headaches that are refractory to treatment. The condition is best viewed as a syndrome rather than a diagnosis. The headache can mimic chronic migraine and chronic tension-type headache, and it is also important to exclude secondary causes, particularly headaches due to alterations in CSF pressure and volume. A large proportion of NDPH sufferers have migrainous features to their headache and should be managed with treatments used for treating migraine. A small group of NDPH sufferers may have intractable headaches that are refractory to treatment.

Impact of GP direct-access computerised tomography for the investigation of chronic daily headache.

BACKGROUND: Chronic daily headache is a major healthcare problem, with significant resource implications for specialist services. Since 1999, GPs in Greater Glasgow have had direct access to computerised tomography (CT) for investigation of chronic daily headache. AIM: The purpose of this study is to assess the significance of pathology, impact of the service, and GP satisfaction. METHOD: The direct-access CT findings in patients between 1999 and 2007 were reviewed. Radiological reports were reviewed for abnormal findings by a radiologist. A neurologist reviewed those cases with abnormalities to assess their potential causation in presenting symptoms. A questionnaire was sent to the referring GP for every patient referred for direct-access CT. Data from the Information Services Division of NHS National Services Scotland was used to estimate potential cost benefits. RESULTS: A total of 4404 CT scans were performed. Abnormal findings were reported in 461 (10.5%), and the reported abnormalities were considered a potential causative factor for the presenting symptoms in 60 patients (1.4%). Other abnormalities mostly resulted from established cerebrovascular disease and atrophy; 986 GP questionnaires were analysed. The major body of GP opinion (n = 460, 47%) indicated that direct-access CT was their preferred choice for referral of chronic daily headache. If direct-access CT was not available, neurology (n = 448, 45%) and general medicine (n = 379, 38%) would be the commonest referral choices. This study also reveals that 86% did not require further specialist referral. Projecting the GP questionnaire data to the study group gave an approximate cost saving of at least £86 681.81. CONCLUSION: Direct-access CT is now the preferred choice of management for patients with chronic daily headache in primary care. Patients and GPs are reassured by a normal scan in the majority of cases. There may be cost savings, although confirmation of cost-effectiveness would require further study.

Evidence base for the medical treatments used in cluster headache.

Cluster headache (CH) is a strictly unilateral headache that occurs in association with cranial autonomic features. It is an excruciating syndrome and is probably one of the most painful conditions known to exist, with some female patients describing each attack as being worse than childbirth. CH responds to specific therapies, thereby underlying the importance of distinguishing it from other primary headache syndromes and initiating appropriate treatments. This article reviews the evidence base for the medical treatments used in CH.