An open-label observational study and meta-analysis of non-invasive vagus nerve stimulation in medically refractory chronic cluster headache

BACKGROUND: Many patients with cluster headache (CH) are inadequately controlled by current treatment options. Non-invasive vagus nerve stimulation (nVNS) is reported to be effective in the management of CH though some studies suggest that it is ineffective. OBJECTIVE: To assess the safety and efficacy of nVNS in chronic cluster headache (CCH) patients. METHOD: We prospectively analysed data from 40 patients with refractory CCH in this open-label, observational study. Patients were seen in tertiary headache clinics at the National Hospital for Neurology and Neurosurgery and trained to use nVNS as preventative therapy. Patients were reivewed at one month and then three-monthly from onset. The primary endpoint was number of patients achieving ≥50% reduction in attack frequency at 3  months. A meta-analysis of all published studies evaluating the efficacy of nVNS in CCH was also conducted. We searched MEDLINE and EMBASE for all studies investigating the use of nVNS as a preventive or adjunctive treatment for CCH with five or more participants. Combined mean difference and responder proportions with 95% confidence intervals (CI) were calculated from the included studies. RESULTS: 17/40 patients (43%) achieved ≥50% reduction in attack frequency at 3  months. There was a significant reduction in monthly attack frequency from a baseline of 124 (±67) attacks to 79 (±63) attacks in month 3 (mean difference 44.7; 95% CI 25.1 to 64.3; p < 0.001). In month 3, there was also a 1.2-point reduction in average severity from a baseline Verbal Rating Scale of 8/10 (95% CI 0.5 to 1.9; p = 0.001). Four studies, along with the present study, were deemed eligible for meta-analysis, which showed a responder proportion of 0.35 (95% CI 0.07 to 0.69, n = 137) and a mean reduction in headache frequency of 35.3 attacks per month (95% CI 11.0 to 59.6, n = 108), from a baseline of 105 (±22.7) attacks per month. CONCLUSION: This study highlights the potential benefit of nVNS in CCH, with significant reductions in headache frequency and severity. To better characterise the effect, randomised sham-controlled trials are needed to confirm the beneficial response of VNS reported in some, but not all, open-label studies

Trigeminal microvascular decompression for short-lasting unilateral neuralgiform headache attacks

A significant proportion of patients with short-lasting unilateral neuralgiform headache attacks (SUNHA) are refractory to medical treatments. Neuroimaging studies have suggested a role for ipsilateral trigeminal neurovascular conflict with morphological changes in the pathophysiology of this disorder. We present the outcome of an uncontrolled open-label prospective single centre study conducted between 2012 and 2020, to evaluate the efficacy and safety of trigeminal microvascular decompression in refractory chronic SUNHA with magnetic resonance imaging evidence of trigeminal neurovascular conflict ipsilateral to the pain side. Primary endpoint was the proportion of patients who achieved an "excellent response", defined as 90-100% weekly reduction in attack frequency, or "good response", defined as a reduction in weekly headache attack frequency between 75% and 89% at final follow-up, compared to baseline. These patients were defined as responders. The study group consisted of 47 patients of whom 31 had SUNCT and 16 had SUNA (25 females, mean age ± SD 55.2 years ± 14.8). Participants failed to respond or tolerate a mean of 8.1 (±2.7) preventive treatments pre-surgery. Magnetic resonance imaging of the trigeminal nerves (n = 47 patients, n = 50 symptomatic trigeminal nerves) demonstrated ipsilateral neurovascular conflict with morphological changes in 39/50 (78.0%) symptomatic nerves and without morphological changes in 11/50 (22.0%) symptomatic nerves. Post-operatively, 37/47 (78.7%) patients obtained either an excellent or a good response. Ten patients (21.3%, SUNCT = 7 and SUNA = 3) reported no post-operative improvement. The mean post-surgery follow-up was 57.4 ± 24.3 months (range 11-96 months). At final follow-up, 31 patients (66.0%) were excellent/good responders. Six patients experienced a recurrence of headache symptoms. There was no statistically significant difference between SUNCT and SUNA in the response to surgery (p = 0.463). Responders at the last follow-up were however more likely not to have interictal pain (77.42% vs 22.58%, p = 0.021) and to show morphological changes on the magnetic resonance imaging (78.38% vs 21.62%, p = 0.001). The latter outcome was confirmed in the Kaplan Meyer analysis, where patients with no morphological changes were more likely to relapse overtime compared to those with morphological changes (p = 0.0001). All but one patient who obtained an excellent response without relapse, discontinued their preventive medications. Twenty-two post-surgery adverse events occurred in 18 patients (46.8%) but no mortality or severe neurological deficit was seen. Trigeminal microvascular decompression may be a safe and effective long-term treatment for short-lasting unilateral neuralgiform headache attacks patients with magnetic resonance evidence of neurovascular conflict with morphological changes

An open-label observational study and meta-analysis of non-invasive vagus nerve stimulation in medically refractory chronic cluster headache

BackgroundMany patients with cluster headache (CH) are inadequately controlled by current treatment options. Non-invasive vagus nerve stimulation (nVNS) is reported to be effective in the management of CH though some studies suggest that it is ineffective.ObjectiveTo assess the safety and efficacy of nVNS in chronic cluster headache (CCH) patients.MethodWe prospectively analysed data from 40 patients with refractory CCH in this open-label, observational study. Patients were seen in tertiary headache clinics at the National Hospital for Neurology and Neurosurgery and trained to use nVNS as preventative therapy. Patients were reivewed at one month and then three-monthly from onset. The primary endpoint was number of patients achieving ≥50% reduction in attack frequency at 3  months. A meta-analysis of all published studies evaluating the efficacy of nVNS in CCH was also conducted. We searched MEDLINE and EMBASE for all studies investigating the use of nVNS as a preventive or adjunctive treatment for CCH with five or more participants. Combined mean difference and responder proportions with 95% confidence intervals (CI) were calculated from the included studies.Results17/40 patients (43%) achieved ≥50% reduction in attack frequency at 3  months. There was a significant reduction in monthly attack frequency from a baseline of 124 (±67) attacks to 79 (±63) attacks in month 3 (mean difference 44.7; 95% CI 25.1 to 64.3; p &lt; 0.001). In month 3, there was also a 1.2-point reduction in average severity from a baseline Verbal Rating Scale of 8/10 (95% CI 0.5 to 1.9; p = 0.001). Four studies, along with the present study, were deemed eligible for meta-analysis, which showed a responder proportion of 0.35 (95% CI 0.07 to 0.69, n = 137) and a mean reduction in headache frequency of 35.3 attacks per month (95% CI 11.0 to 59.6, n = 108), from a baseline of 105 (±22.7) attacks per month.ConclusionThis study highlights the potential benefit of nVNS in CCH, with significant reductions in headache frequency and severity. To better characterise the effect, randomised sham-controlled trials are needed to confirm the beneficial response of VNS reported in some, but not all, open-label studies

Investigating the impact of financial concerns on symptoms of depression in UK healthcare workers: data from the UK-REACH nationwide cohort study

BACKGROUND: Exploration of the association between financial concerns and depression in UK healthcare workers (HCWs) is paramount given the current 'cost of living crisis', ongoing strike action and recruitment/retention problems in the National Health Service. AIMS: To assess the impact of financial concerns on the risk of depression in HCWs, how these concerns have changed over time and what factors might predict financial concerns. METHOD: We used longitudinal survey data from a UK-wide cohort of HCWs to determine whether financial concerns at baseline (December 2020 to March 2021) were associated with depression (measured with the Public Health Questionnaire-2) at follow-up (June to October 2022). We used logistic regression to examine the association between financial concerns and depression, and ordinal logistic regression to establish predictors of developing financial concerns. RESULTS: A total of 3521 HCWs were included. Those concerned about their financial situation at baseline had higher odds of developing depressive symptoms at follow-up. Financial concerns increased in 43.8% of HCWs and decreased in 9%. Those in nursing, midwifery and other nursing roles had over twice the odds of developing financial concerns compared with those in medical roles. CONCLUSIONS: Financial concerns are increasing in prevalence and predict the later development of depressive symptoms in UK HCWs. Those in nursing, midwifery and other allied nursing roles may have been disproportionately affected. Our results are concerning given the potential effects on sickness absence and staff retention. Policy makers should act to alleviate financial concerns to reduce the impact this may have on a discontent workforce plagued by understaffing

Coverage, completion and outcomes of COVID-19 risk assessments in a multi-ethnic nationwide cohort of UK healthcare workers: a cross-sectional analysis from the UK-REACH Study

INTRODUCTION: There are limited data on the outcomes of COVID-19 risk assessment in healthcare workers (HCWs) or the association of ethnicity, other sociodemographic and occupational factors with risk assessment outcomes. METHODS: We used questionnaire data from UK-REACH (UK Research study into Ethnicity And COVID-19 outcomes in Healthcare workers), an ethnically diverse, nationwide cohort of UK HCWs. We derived four binary outcomes: (1) offered a risk assessment; (2) completed a risk assessment; (3) working practices changed as a result of the risk assessment; (4) wanted changes to working practices after risk assessment but working practices did not change.We examined the association of ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk variables on our outcomes using multivariable logistic regression. RESULTS: 8649 HCWs were included in total. HCWs from ethnic minority groups were more likely to report being offered a risk assessment than white HCWs, and those from Asian and black ethnic groups were more likely to report having completed an assessment if offered. Ethnic minority HCWs had lower odds of reporting having their work change as a result of risk assessment. Those from Asian and black ethnic groups were more likely to report no changes to their working practices despite wanting them.Previous SARS-CoV-2 infection was associated with lower odds of being offered a risk assessment and having adjustments made to working practices. DISCUSSION: We found differences in risk assessment outcomes by ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk factors. These findings are concerning and warrant further research using actual (rather than reported) risk assessment outcomes in an unselected cohort

Healthcare workers’ views on mandatory SARS-CoV-2 vaccination in the UK: A cross-sectional, mixed-methods analysis from the UK-REACH study

Background: Several countries now have mandatory SARS-CoV-2 vaccination for healthcare workers (HCWs) or the general population. HCWs’ views on this are largely unknown. Using data from the nationwide UK-REACH study we aimed to understand UK HCW's views on improving SARS-CoV-2 vaccination coverage, including mandatory vaccination. // Methods: Between 21st April and 26th June 2021, we administered an online questionnaire via email to 17 891 UK HCWs recruited as part of a longitudinal cohort from across the UK who had previously responded to a baseline questionnaire (primarily recruited through email) as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) nationwide prospective cohort study. We categorised responses to a free-text question “What should society do if people do not get vaccinated against COVID-19?” using qualitative content analysis. We collapsed categories into a binary variable: favours mandatory vaccination or not, using logistic regression to calculate its demographic predictors, and its occupational, health, and attitudinal predictors adjusted for demographics. // Findings: Of 5633 questionnaire respondents, 3235 answered the free text question. Median age of free text responders was 47 years (IQR 36–56) and 2705 (74.3%) were female. 18% (n = 578) favoured mandatory vaccination (201 [6%] participants for HCWs and others working with vulnerable populations; 377 [12%] for the general population), but the most frequent suggestion was education (32%, n = 1047). Older HCWs (OR 1.84; 95% CI 1.44–2.34 [≥55 years vs 16 years to <40 years]), HCWs vaccinated against influenza (OR 1.49; 95% CI 1.11–2.01 [2 vaccines vs none]), and with more positive vaccination attitudes generally (OR 1.10; 95% CI 1.06–1.15) were more likely to favour mandatory vaccination, whereas female HCWs (OR= 0.79, 95% CI 0.63–0.96, vs male HCWs) and Black HCWs (OR=0.46, 95% CI 0.25–0.85, vs white HCWs) were less likely to. // Interpretation: Only one in six of the HCWs in this large, diverse, UK-wide sample favoured mandatory vaccination. Building trust, educating, and supporting HCWs who are hesitant about vaccination may be more acceptable, effective, and equitable

Investigating the impact of financial concerns on symptoms of depression in UK healthcare workers: data from the UK-REACH nationwide cohort study

Background Exploration of the association between financial concerns and depression in UK healthcare workers (HCWs) is paramount given the current ‘cost of living crisis’, ongoing strike action and recruitment/retention problems in the National Health Service. Aims To assess the impact of financial concerns on the risk of depression in HCWs, how these concerns have changed over time and what factors might predict financial concerns. Method We used longitudinal survey data from a UK-wide cohort of HCWs to determine whether financial concerns at baseline (December 2020 to March 2021) were associated with depression (measured with the Public Health Questionnaire-2) at follow-up (June to October 2022). We used logistic regression to examine the association between financial concerns and depression, and ordinal logistic regression to establish predictors of developing financial concerns. Results A total of 3521 HCWs were included. Those concerned about their financial situation at baseline had higher odds of developing depressive symptoms at follow-up. Financial concerns increased in 43.8% of HCWs and decreased in 9%. Those in nursing, midwifery and other nursing roles had over twice the odds of developing financial concerns compared with those in medical roles. Conclusions Financial concerns are increasing in prevalence and predict the later development of depressive symptoms in UK HCWs. Those in nursing, midwifery and other allied nursing roles may have been disproportionately affected. Our results are concerning given the potential effects on sickness absence and staff retention. Policy makers should act to alleviate financial concerns to reduce the impact this may have on a discontent workforce plagued by understaffing

Multidisciplinary consensus guideline for the diagnosis and management of spontaneous intracranial hypotension

BACKGROUND: We aimed to create a multidisciplinary consensus clinical guideline for best practice in the diagnosis, investigation and management of spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid leak based on current evidence and consensus from a multidisciplinary specialist interest group (SIG). METHODS: A 29-member SIG was established, with members from neurology, neuroradiology, anaesthetics, neurosurgery and patient representatives. The scope and purpose of the guideline were agreed by the SIG by consensus. The SIG then developed guideline statements for a series of question topics using a modified Delphi process. This process was supported by a systematic literature review, surveys of patients and healthcare professionals and review by several international experts on SIH. RESULTS: SIH and its differential diagnoses should be considered in any patient presenting with orthostatic headache. First-line imaging should be MRI of the brain with contrast and the whole spine. First-line treatment is non-targeted epidural blood patch (EBP), which should be performed as early as possible. We provide criteria for performing myelography depending on the spine MRI result and response to EBP, and we outline principles of treatments. Recommendations for conservative management, symptomatic treatment of headache and management of complications of SIH are also provided. CONCLUSIONS: This multidisciplinary consensus clinical guideline has the potential to increase awareness of SIH among healthcare professionals, produce greater consistency in care, improve diagnostic accuracy, promote effective investigations and treatments and reduce disability attributable to SIH

Association of Clinical and Neuroanatomical Factors With Response to Ventral Tegmental Area DBS in Chronic Cluster Headache

Background: Deep brain stimulation (DBS) of the ventral tegmental area (VTA) is a surgical treatment option for selected patients with refractory chronic cluster headache (CCH). We aimed to identify clinical and structural neuroimaging factors associated with response to VTA DBS in CCH. // Methods: This prospective observational cohort study examines consecutive patients with refractory CCH treated with VTA DBS by a multidisciplinary team in a single tertiary neuroscience centre as part of usual care. Headache diaries and validated questionnaires were completed at baseline and regular follow up intervals. All patients underwent T1-weighted structural MRI prior to surgery. We compared clinical features using multivariable logistic regression, and neuroanatomical differences using voxel-based morphometry (VBM) between responders and non-responders. // Results: Over a ten-year period, 43 patients (mean age 53 years, SD 11.9), including 29 males, with a mean duration of CCH 12 years (SD 7.4), were treated and followed up for at least one year (mean follow-up duration 5.6 years). Overall, there was a statistically significant improvement in median attack frequency from 140 to 56 per month (Z = -4.95, p <0.001), attack severity from 10/10 to 8/10 (Z = -4.83, p <0.001) and duration from 110 to 60 minutes (Z = -3.48, p <0.001). Twenty-nine (67.4%) patients experienced ≥50% improvement in attack frequency and were therefore classed as responders. There were no serious adverse events. The most common side effects were discomfort or pain around the battery site (seven patients) and transient diplopia and/or oscillopsia (six patients). There were no differences in demographics, headache characteristics, or comorbidities between responders and non-responders. VBM identified increased neural density in non-responders in several brain regions, including the orbitofrontal cortex, anterior cingulate cortex, anterior insula, and amygdala which were statistically significant (p <0.001). // Discussion: VTA DBS showed no serious adverse events, and, although there was no placebo control, was effective in approximately two-thirds of patients at long-term follow up. This study did not reveal any reliable clinical predictors of response. However, non-responders had increased neural density in brain regions linked to processing of pain and autonomic function, both of which are prominent in the pathophysiology of CCH