Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes.

BACKGROUND: Device-detected atrial high-rate episodes (AHREs) are atrial arrhythmias detected by implanted cardiac devices. AHREs resemble atrial fibrillation but are rare and brief. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram [ECG]) justifies the initiation of anticoagulants is not known. METHODS: We conducted an event-driven, double-blind, double-dummy, randomized trial involving patients 65 years of age or older who had AHREs lasting for at least 6 minutes and who had at least one additional risk factor for stroke. Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding. RESULTS: The analysis population consisted of 2536 patients (1270 in the edoxaban group and 1266 in the placebo group). The mean age was 78 years, 37.4% were women, and the median duration of AHREs was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed. A primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08; P = 0.15). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). CONCLUSIONS: Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding. The incidence of stroke was low in both groups. (Funded by the German Center for Cardiovascular Research and others; NOAH-AFNET 6 ClinicalTrials.gov number, NCT02618577; ISRCTN number, ISRCTN17309850.).

Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24†h.

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

New migraine drugs: A critical appraisal of the reason why the majority of migraine patients do not receive an adequate medication.

The last three decades have produced several novel and efficient medications to treat migraine attacks and reduce attack frequency. Additionally, promising approaches for the development of acute therapy and migraine prophylaxis continue to be pursued. At the same time as we witness the development of better and more efficient medications with continuously fewer side effects, we also realise that the high cost of such therapies means that only a minority of migraine patients who could benefit from these medications can afford them. Furthermore, information on cost-effectiveness is still lacking. Here, we compare availiable data, highlight open questions and suggest trials to close knowledge gaps. With good reason, our medicine is evidence-based. However, if this evidence is not collected, our decisions will continue to be based on marketing and assumptions. At the moment, we are not doing justice to our patients.

Guidelines of the International Headache Society for controlled trials of pharmacological preventive treatment for persistent post-traumatic headache attributed to mild traumatic brain injury.

BACKGROUND: Persistent headache attributed to traumatic injury to the head is divided into two subtypes, one attributed to moderate or severe traumatic injury and another attributed to mild traumatic injury (i.e., concussion). The latter is much more prevalent, in part because more than 90% of cases with traumatic brain injury are classified as mild. The pathophysiology of persistent post-traumatic headache is poorly understood and the underlying mechanisms are likely multifactorial. There is currently no approved treatment specifically for persistent post-traumatic headache, and management strategies rely on medications used for migraine or tension-type headache. Therefore, high-quality trials are urgently needed to support clinical decision-making and optimize management strategies. International guidelines can facilitate appropriate trial design and ensure the acquisition of high-quality data evaluating the efficacy, tolerability, and safety of available and novel pharmacological therapies for the preventive treatment of persistent post-traumatic headache. METHODS: The development of this guideline was based on a literature review of available studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, along with a review of previously published guidelines for controlled trials of preventive treatment for episodic and chronic migraine. The identified literature was critically appraised, and due to the scarcity of scientific evidence, recommendations were primarily based on the consensus of experts in the field. OBJECTIVE: To provide guidelines for designing state-of-the-art controlled clinical trials aimed at evaluating the effectiveness of preventive treatments for persistent post-traumatic headache attributed to mild traumatic brain injury.

International Headache Society global practice recommendations for the acute pharmacological treatment of migraine.

BACKGROUND: In an effort to improve migraine management around the world, the International Headache Society (IHS) has here developed a list of practical recommendations for the acute pharmacological treatment of migraine. The recommendations are categorized into optimal and essential, in order to provide treatment options for all possible settings, including those with limited access to migraine medications. METHODS: An IHS steering committee developed a list of clinical questions based on practical issues in the management of migraine. A selected group of international senior and junior headache experts developed the recommendations, following expert consensus and the review of available national and international headache guidelines and guidance documents. Following the initial search, a bibliography of twenty-one national and international guidelines was created and reviewed by the working group. RESULTS: A total of seventeen questions addressing different aspects of acute migraine treatment have been outlined. For each of them we provide an optimal recommendation, to be used whenever possible, and an essential recommendation to be used when the optimal level cannot be attained. CONCLUSION: Adoption of these international recommendations will improve the quality of acute migraine treatment around the world, even where pharmacological options remain limited.

Sustained benefits of onabotulinumtoxinA treatment in chronic migraine: An analysis of the pooled Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) randomized controlled trials.

OBJECTIVE: To characterize the long-term (56-week) benefits of continuous onabotulinumtoxinA treatment response in individuals with chronic migraine (CM) who achieved reduction to <15 headache days/month with treatment. BACKGROUND: There are limited data exploring reductions in monthly headache days to levels consistent with episodic migraine among those experiencing CM. Understanding the impact of sustained preventive treatment response in CM can provide important information about the impact of successful therapy. METHODS: The two Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy trials of onabotulinumtoxinA in adults included a 24-week, randomized, double-blind, placebo-controlled phase and a 32-week open-label phase. Data were pooled to determine proportions of individuals with <15 headache days/month while on treatment during several time periods in the double-blind phase (Weeks 21-24; any 12 consecutive weeks; Weeks 13-24) and the entire study (Weeks 53-56; any 12 consecutive weeks; any 4-week period). We assessed the long-term impact on mean monthly headache days and changes from baseline on the six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2.1). RESULTS: We analyzed 1384 participants with chronic migraine (double-blind: onabotulinumtoxinA, n = 688; placebo, n = 696; open-label: n = 688 [onabotulinumtoxinA]). The discontinuation rates prior to the completion of the full 56-week treatment period for onabotulinumtoxinA and placebo were 25.4% (n = 175) and 29.3% (n = 204), respectively. During Weeks 13-24 of the double-blind phase, significantly more onabotulinumtoxinA-treated (386/688 [56.1%]) than placebo-treated (342/696 [49.1%]) individuals had <15 headache days/month (p = 0.010), with fewer monthly headache days for onabotulinumtoxinA versus placebo responders. The proportions of participants achieving <15 monthly headache days with onabotulinumtoxinA were 60.9% (419/688) at Weeks 25-56, 81.1% (558/688) at Weeks 53-56, and 79.4% (546/688) during any consecutive 12-week period. Mean changes from baseline on the HIT-6 and MSQv2.1 questionnaire surpassed within-group minimal important difference thresholds in all periods. At Week 24, onabotulinumtoxinA-treated participants who achieved <15 monthly headache days during Weeks 21-24 had a greater mean HIT-6 score reduction (-6.5 vs. -1.4) and greater mean MSQv2.1 Role-Function Restrictive score improvements (21.3 vs. 6.4) than those who did not achieve <15 monthly headache days during the same period. CONCLUSIONS: Participants who achieved <15 monthly headache days with onabotulinumtoxinA treatment achieved meaningful benefits in headache-related disability and migraine-specific quality of life compared with those who remained at or above the 15-monthly headache days threshold. Sustained benefits observed over 56 weeks support long-term onabotulinumtoxinA use for the prevention of CM.

Guidelines Update: Guidelines of the International Headache Society for controlled trials of preventive treatment of migraine in children and adolescents, 1st edition - An experience-based update.

BACKGROUND: Recent experience in designing and running clinical trials on new medications for the prevention of migraine in children and adolescents highlighted the need for revision of the 1st edition of the International Headache Society Guidelines for clinical trials of preventive treatment of migraine in children and adolescents which were published in 2019. METHODS: The authors of the 1st edition of the guidelines formed an informal focus group with aims of appraising the performance of the guidelines, clarifying any ambiguity and providing improvements, where needed, based on personal experience and expert analysis. RESULTS: This review and the following update were able to address issues related to the classification of migraine, the duration of migraine attacks, the age groups of children and adolescents, the use of electronic diaries, the assessment of outcome measures, the need for an interim analysis and the issues related to placebo response. CONCLUSIONS: This update provides necessary clarifications of the guidelines in order to enable better design and running of future clinical trials for the preventive treatment of migraine in children and adolescents.

Safety and tolerability of monoclonal antibodies targeting the CGRP pathway and gepants in migraine prevention: A systematic review and network meta-analysis.

BACKGROUND: Direct comparisons of the tolerability and safety of migraine preventive treatments targeting the calcitonin gene-related peptide pathway are lacking. This study aimed to compare the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies and gepants in migraine prevention. METHODS: A network meta-analysis of phase 3 randomized controlled trials assessing the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies (erenumab, eptinezumab, fremanezumab, or galcanezumab) and gepants (atogepant, rimegepant) in migraine prevention was performed. Primary outcomes were treatment-emergent adverse events and serious adverse events. Secondary outcomes included any adverse events, adverse events leading to treatment discontinuation and individual adverse events. RESULTS: We included 19 randomized controlled trials, comprising 14,584 patients. Atogepant 120 mg (OR 2.22, 95% CI [1.26, 3.91]) and galcanezumab 240 mg (OR 1.63, 95% CI [1.33, 2.00]) showed the largest odds of treatment-emergent adverse events compared to placebo. While eptinezumab 30 mg had greater odds of adverse events leading to treatment discontinuation (OR 2.62, 95% CI [1.03,6.66]). No significant differences in serious adverse events were found between active treatments and placebo. Eptinezumab was associated with the lowest odds of treatment-emergent adverse events and serious adverse events compared to placebo, whereas erenumab was associated with the lowest odds of any adverse events and quarterly fremanezumab with the lowest odds of treatment discontinuation due to adverse events. CONCLUSION: Monoclonal antibodies targeting the calcitonin gene-related peptide pathway and gepants are a safe and well tolerated option for migraine prevention.

Efficacy and safety of monoclonal antibodies targeting CGRP in migraine prevention. GRADE tables elaborated by the ad hoc working group of the International Headache Society.

OBJECTIVES: Grading of Recommendations, Assessment Development and Evaluation (GRADE) tables were created using a standardized and independent assessment of the efficacy and side effects of treatments with monoclonal antibodies (mAb) against calcitonin gene-related peptide (CGRP) or the CGRP receptor for the prevention of migraine. We hope to provide support for author groups writing national or regional treatment or management guidelines for migraine prevention. METHODS: We formulated patient/population, intervention, comparison and outcomes (PICO) questions for the efficacy and safety of mAb against CGRP or the CGRP-receptor for the prevention of migraine attacks. We performed a systematic literature research for randomized studies with eptinezumab, erenumab, fremanezumab and galcanezumab and a pooled analysis was done, using RevMan 5.4 software. For dichotomous outcomes we used risk ratio, and for continuous outcomes we used the mean difference to compare and summarize the evidence between groups. The evidence across studies, for each outcome, except serious adverse events, was assessed using GRADE evidence tables. Additionally, we report the serious adverse effects in the tables of the characteristics of the studies. RESULTS: All mAb are superior to placebo for the reduction in monthly migraine days (days in which a headache consistent with migraine occurred) in participants with episodic and chronic migraine. There are no major differences between the mAb. CONCLUSIONS: The GRADE evidence summary tables provided will support author groups to write treatment guidelines for the prevention of migraine with mAb.

Headache attributed to SARS-CoV-2 infection, vaccination and the impact on primary headache disorders of the COVID-19 pandemic: A comprehensive review.

OBJECTIVE: The objective is to summarize the knowledge on the epidemiology, pathophysiology and management of secondary headache attributed to SARS-CoV-2 infection and vaccination; as well as to delineate their impact on primary headache disorders. METHODS: This is a narrative review of the literature regarding primary and secondary headache disorders in the setting of COVID-19 pandemic. We conducted a literature search in 2022 on PubMed, with the keywords "COVID 19" or "vaccine" and "headache" to assess the appropriateness of all published articles for their inclusion in the review. RESULTS: Headache is a common and sometimes difficult-to-treat symptom of both the acute and post-acute phase of SARS-CoV-2 infection. Different pathophysiological mechanisms may be involved, with the trigeminovascular system as a plausible target. Specific evidence-based effective therapeutic options are lacking at present. Headache attributed to SARS-CoV-2 vaccinations is also common, its pathophysiology being unclear. People with primary headache disorders experience headache in the acute phase of COVID-19 and after vaccination more commonly than the general population. Pandemic measures, forcing lifestyle changes, seemed to have had a positive impact on migraine, and changes in headache care (telemedicine) have been effectively introduced. CONCLUSIONS: The ongoing COVID-19 pandemic is a global challenge, having an impact on the development of secondary headaches, both in people with or without primary headaches. This has created opportunities to better understand and treat headache and to potentiate strategies to manage patients and ensure care.

Guidelines of the International Headache Society for Controlled Clinical Trials in Idiopathic Intracranial Hypertension.

The quality of clinical trials is essential to advance treatment, inform regulatory decisions and meta-analysis. With the increased incidence of idiopathic intracranial hypertension and the emergence of clinical trials for novel therapies in this condition, the International Headache Society Guidelines for Controlled Clinical Trials in Idiopathic Intracranial Hypertension aims to establish guidelines for designing state-of-the-art controlled clinical trials for idiopathic intracranial hypertension.

Cognitive deficits in patients with peripheral vestibular dysfunction.

BACKGROUND AND PURPOSE: Previous studies demonstrated cognitive deficits in patients with peripheral vestibulopathy (PVP) with dysfunction of spatial navigation and orientation, but also documented cognitive decline in nonspatial abilities. This study evaluates cognitive deficits in patients with unilateral vestibulopathy (UVP) as well as bilateral vestibulopathy (BVP) in multiple cognitive domains using common screening tests to reliably detect these deficits in clinical practice. METHODS: This prospective study compared patients with UVP and BVP to age- and sex-matched healthy controls (HC). Tests included the Alzheimer's Disease Assessment Scale (ADAS), Mini-Mental Status Examination (MMSE), Trail Making Test Part A and B, Clock Drawing Task, Executive Interview-25 (EXIT25), Dementia Detection (DemTect), and the Judgment of Line Orientation (JLO). The Montgomery-Åsberg Depression Rating Scale was used to control for depression. Videonystagmography objectively reconfirmed PVP. The Vertigo Symptoms Scale and the Dizziness Handicap Inventory were used to assess for symptom severity and restrictions of activities of daily living. RESULTS: Eighty-one patients (65 UVP, 16 BVP) were compared to 55 HC. Patients showed impairment in ADAS, MMSE, DemTect, EXIT25, and JLO. No differences between UVP and BVP were detected. The relative risk (RR) estimates of developing cognitive deficits following PVP were increased. The RR for the ADAS was higher in BVP (RR = 4.91, 95% confidence interval [CI] = 1.87-12.9, p = 0.001) than in UVP (RR = 3.75, 95% CI = 1.65-8.51, p = 0.002), but was similar for the MMSE and DemTect between groups. CONCLUSIONS: Patients with PVP showed deficits in multiple cognitive domains including nonspatial cognitive abilities. Vestibulopathy could be a risk factor for the development of cognitive impairment.

Numbers needed to treat or harm and likelihood of being helped versus harmed for fremanezumab in patients who had prior inadequate response to two to four classes of migraine preventive medications: A post hoc analysis.

OBJECTIVE: This study aimed to determine the number needed to treat (NNT), number needed to harm (NNH), and likelihood of being helped or harmed (LHH) in a post hoc analysis of the phase 3b FOCUS trial. BACKGROUND: Fremanezumab, a humanized monoclonal antibody that selectively targets calcitonin gene-related peptide (CGRP), has demonstrated efficacy, tolerability, and safety in adults with episodic migraine (EM) or chronic migraine (CM), with documented previous inadequate response to two to four classes of migraine preventive medications. METHODS: In the 12-week double-blind period of the FOCUS study, patients were randomized (1:1:1) to quarterly fremanezumab, monthly fremanezumab, or matched monthly placebo. NNT was based on responder analysis, defined as ≥50% reduction in monthly average number of migraine days at 12 weeks. NNH was based on discontinuations due to adverse events (AEs). RESULTS: Among patients with CM (n = 509), response rates and discontinuation rates were 27% (45/169) and 0 for quarterly fremanezumab, 29% (50/173) and 2% (3/173) for monthly fremanezumab, and 8% (13/167) and <1% (1/167) for placebo, respectively. These results translated to NNTs of 5.3 and 4.7, NNHs of 1000 and 88, and LHHs of 188 and 19 for quarterly and monthly fremanezumab, respectively. Among patients with EM (n = 328), response rates were 47% (50/107) for quarterly fremanezumab, 43% (47/110) for monthly fremanezumab, and 10% (11/111) for placebo. Discontinuation rates were <1% (n = 1) in all three groups. These results translated to NNTs of 2.7 and 3.0, NNHs of 1000 and 1000, and LHHs of 368 and 328 for quarterly and monthly fremanezumab, respectively. CONCLUSIONS: The NNT, NNH, and LHH for quarterly and monthly fremanezumab compare favorably with those for traditional oral preventive medications, including topiramate, valproate, and propranolol.

Eptinezumab improved patient-reported outcomes in patients with migraine and medication-overuse headache: Subgroup analysis of the randomized PROMISE-2 trial.

OBJECTIVE: To evaluate the effect of eptinezumab on patient-reported outcomes in patients with chronic migraine (CM) and medication-overuse headache (MOH). BACKGROUND: MOH is a secondary headache disorder commonly occurring in patients with CM and associated with functional and psychological impairments. Medication overuse and monthly headache and migraine days were reduced with eptinezumab compared with placebo as published previously; however, these outcomes do not fully capture the burden of migraine and treatment effect. METHODS: PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled trial in adults with CM. Patients were randomized (1:1:1) to receive eptinezumab 100 mg, eptinezumab 300 mg, or placebo (up to 2 doses, 12 weeks apart). Patients completed the following patient-reported outcomes: 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), patient-identified most bothersome symptom (PI-MBS), and 36-item Short-Form Health Survey (SF-36). RESULTS: A total of 431 CM patients (139, 147, and 145 patients in the eptinezumab 100 mg, eptinezumab 300 mg, and placebo groups, respectively) had MOH diagnosed at screening (40.2% of the total PROMISE-2 population [n = 1072]). In CM with MOH patients, both doses of eptinezumab were associated with clinically meaningful improvements in mean HIT-6 total scores by week 4 and remained improved throughout the 24-week study. Responder rates for individual HIT-6 items were greater with eptinezumab than with placebo at all time points. At week 12, almost twice as many eptinezumab-treated patients indicated the PGIC was "much" or "very much" improved (58.5% [79/135, 100 mg] and 67.4% [95/147, 300 mg] vs. 35.8% [48/134, placebo]). Patients in the eptinezumab groups showed numerically greater improvements over placebo in the PI-MBS and SF-36 scores. CONCLUSIONS: This subgroup analysis in patients with CM/MOH at baseline suggests that eptinezumab treatment is associated with early, sustained, and clinically meaningful improvements in patient-reported outcomes.

Towards personalized antithrombotic management with drugs and devices across the cardiovascular spectrum.

Intravascular thrombus formation and embolization are among the most frequent events leading to a number of cardiovascular conditions with high morbidity and mortality. The underlying causes are stasis of the circulating blood, genetic and acquired coagulation disorders, and reduced antithrombotic or prothrombotic properties of the vascular wall (Virchow's triad). In the venous system, intravascular thrombi can cause venous thrombosis and pulmonary and even peripheral embolism including ischaemic stroke [through a patent foramen ovale (PFO)]. Thrombi in the left atrium and its appendage or ventricle form in the context of atrial fibrillation and infarction, respectively. Furthermore, thrombi can form on native or prosthetic aortic valves, within the aorta (in particular at sites of ulcers, aortic dissection, and abdominal aneurysms), and in cerebral and peripheral arteries causing stroke and critical limb ischaemia, respectively. Finally, thrombotic occlusion may occur in arteries supplying vital organs such the heart, brain, kidney, and extremities. Thrombus formation and embolization can be managed with anticoagulants and devices depending on where they form and embolize and on patient characteristics. Vitamin K antagonists are preferred in patients with mechanical valves, while novel oral anticoagulants are first choice in most other cardiovascular conditions, in particular venous thromboembolism and atrial fibrillation. As anticoagulants are associated with a risk of bleeding, devices such as occluders of a PFO or the left atrial appendage are preferred in patients with an increased bleeding risk. Platelet inhibitors such as aspirin and/or P2Y12 antagonists are preferred in the secondary prevention of coronary artery disease, stroke, and peripheral artery disease either alone or in combination depending on the clinical condition. A differential and personalized use of anticoagulants, platelet inhibitors, and devices is recommended and reviewed in this article.

[Analgesic use in Germany : Survey of the years 2008 to 2019]. / Schmerzmittelgebrauch in Deutschland : Eine Erhebung über die Jahre 2008 bis 2019.

BACKGROUND: There are previously published data on the per capita use of analgesics in Germany, but only to 2005. In the present analysis, data for the years 2008-2019 were evaluated. The use of prescription and nonprescription analgesics was investigated and possible influencing factors were discussed. MATERIALS AND METHODS: The per capita use of prescription and nonprescription analgesics was determined based on data on prescriptions and cash purchases in pharmacies (IMS Pharmascope®, Wiener Neudorf, Austria). Moreover, an evaluation according to active substances was performed for nonprescription drugs. In addition, pharmaceutical manufacturers' advertising expenditures and changes in distribution channels were analyzed as possible influencing factors. RESULTS: During the observation period 2008-2019, the use of prescription analgesics in Germany increased, while the use of nonprescription analgesics decreased. Single-agent drugs constitute the majority of sales of nonprescription analgesics. The share of combination drugs has decreased in recent years. CONCLUSION: The use of nonprescription analgesics in Germany decreased between 2008 and 2019. The trend as of 1995, which was observed in a previous investigation, is therefore continuing. External factors, such as the increase in advertising expenses or easier access via mail-order pharmacies, do not appear to influence use.

[Consensus statement of the migraine and headache societies (DMKG, ÖKSG, and SKG) on the duration of pharmacological migraine prophylaxis]. / Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe.

Migraine is the most common neurological disorder and can be associated with a high degree of disability. In addition to non-pharmacological approaches to reduce migraine frequency, pharmacological migraine preventatives are available. Evidence-based guidelines from the German Migraine and Headache Society (DMKG), and German Society for Neurology (DGN), Austrian Headache Society (ÖKSG), and Swiss Headache Society (SKG) are available for indication and application. For therapy-relevant questions such as the duration of a pharmacological migraine prevention, no conclusions can be drawn from currently available study data. The aim of this review is to present a therapy consensus statement that integrates the current data situation and, where data are lacking, expert opinions. The resulting current recommendations on the duration of therapy for pharmacological migraine prophylaxis are shown here.

[Consensus statement of the migraine and headache societies (DMKG, ÖKSG, and SKG) on the duration of pharmacological migraine prophylaxis]. / Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe.

Migraine is the most common neurological disorder and can be associated with a high degree of disability. In addition to non-pharmacological approaches to reduce migraine frequency, pharmacological migraine preventatives are available. Evidence-based guidelines from the German Migraine and Headache Society (DMKG), and German Society for Neurology (DGN), Austrian Headache Society (ÖKSG), and Swiss Headache Society (SKG) are available for indication and application. For therapy-relevant questions such as the duration of a pharmacological migraine prevention, no conclusions can be drawn from currently available study data. The aim of this review is to present a therapy consensus statement that integrates the current data situation and, where data are lacking, expert opinions. The resulting current recommendations on the duration of therapy for pharmacological migraine prophylaxis are shown here.

[Chronic Back Pain]. / Chronische Rückenschmerzen.

Chronic back pain is one of the most common diseases in Germany. In many cases, no morphological change is found, so that the genesis remains unspecific in over 90% of patients. This article is intended to provide an overview of drug therapy as well as non-drug measures and summarizes the corresponding guideline recommendations.

Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE): A Randomized, Controlled Trial.

BACKGROUND: Percutaneous closure of the left atrial appendage (LAA) is an alternative to chronic oral anticoagulation to reduce stroke risk in patients with nonvalvular atrial fibrillation. The Amulet IDE trial (Amplatzer Amulet Left Atrial Appendage Occluder IDE Trial) was designed to evaluate the safety and effectiveness of the dual-seal mechanism of the Amulet LAA occluder compared with the Watchman device. METHODS: Patients with nonvalvular atrial fibrillation at increased risk of stroke were randomly assigned (1:1) to undergo percutaneous implantation of a LAA occluder with the Amulet occluder or Watchman device. The primary end points included safety (composite of procedure-related complications, all-cause death, or major bleeding at 12 months), effectiveness (composite of ischemic stroke or systemic embolism at 18 months), and the rate of LAA occlusion at 45 days. Prespecified secondary end points included a composite of all stroke, systemic embolism, or cardiovascular/unexplained death at 18 months, major bleeding at 18 months, and superiority test of the 3 primary end points. RESULTS: A total of 1878 patients were enrolled. The Amulet occluder was noninferior to the Watchman device for the primary safety end point (14.5% versus 14.7%; difference=-0.14 [95% CI, -3.42 to 3.13]; P<0.001 for noninferiority). Major bleeding and all-cause death were similar between groups (10.6% versus 10.0% and 3.9% versus 5.1%, respectively). Procedure-related complications were higher for the Amulet occluder (4.5% versus 2.5%), largely related to more frequent pericardial effusion and device embolization. The Amulet occluder was noninferior to the Watchman device for the primary effectiveness end point (2.8% versus 2.8%; difference=0.00 [95% CI, -1.55 to 1.55]; P<0.001 for noninferiority), and the composite of stroke, systemic embolism, or cardiovascular/unexplained death (5.6% versus 7.7%, difference=-2.12 [95% CI, -4.45 to 0.21]; P<0.001 for noninferiority). The rate of major bleeding was similar between groups (11.6% versus 12.3%; difference=-0.71 [95% CI, -3.72 to 2.31]; P=0.32 for superiority). LAA occlusion was higher for the Amulet occluder than for the Watchman device (98.9% versus 96.8%; difference=2.03 [95% CI, 0.41-3.66]; P<0.001 for noninferiority; P=0.003 for superiority). CONCLUSIONS: The Amulet occluder was noninferior for safety and effectiveness of stroke prevention for nonvalvular atrial fibrillation compared with the Watchman device and superior for LAA occlusion. Procedure-related complications were higher with the Amulet occluder and decreased with operator experience. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02879448.