Long-term safety of OnabotulinumtoxinA treatment in chronic migraine patients: a five-year retrospective study.

Background: Real-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting. Methods: We performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability. Results: 489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; p < 0.001). The MHDs were also reduced by 14.9 days (24.7 to 9.8 days; p < 0.001). Regarding the side effects, 17.5% experienced neck pain, 17.3% headache, 8.5% eyelid ptosis, 7.5% temporal muscle atrophy and 3.2% trapezius muscle atrophy. Furthermore, after longer-term exposure exceeding 5 years, there were no serious adverse events (AE) or treatment discontinuation because of safety or tolerability issues. Conclusion: Treatment with BoNTA led to sustained reductions in migraine frequency, even after long-term exposure exceeding 5 years, with no evidence of new safety concerns.

Cefto Real-Life Study: Real-World Data on the Use of Ceftobiprole in a Multicenter Spanish Cohort.

BACKGROUND: Ceftobiprole is a fifth-generation cephalosporin that has been approved in Europe solely for the treatment of community-acquired and nosocomial pneumonia. The objective was to analyze the use of ceftobiprole medocaril (Cefto-M) in Spanish clinical practice in patients with infections in hospital or outpatient parenteral antimicrobial therapy (OPAT). METHODS: This retrospective, observational, multicenter study included patients treated from 1 September 2021 to 31 December 2022. RESULTS: A total of 249 individuals were enrolled, aged 66.6 ± 15.4 years, of whom 59.4% were male with a Charlson index of four (IQR 2-6), 13.7% had COVID-19, and 4.8% were in an intensive care unit (ICU). The most frequent type of infection was respiratory (55.8%), followed by skin and soft tissue infection (21.7%). Cefto-M was administered to 67.9% of the patients as an empirical treatment, in which was administered as monotherapy for 7 days (5-10) in 53.8% of cases. The infection-related mortality was 11.2%. The highest mortality rates were identified for ventilator-associated pneumonia (40%) and infections due to methicillin-resistant Staphylococus aureus (20.8%) and Pseudomonas aeruginosa (16.1%). The mortality-related factors were age (OR: 1.1, 95%CI (1.04-1.16)), ICU admission (OR: 42.02, 95%CI (4.49-393.4)), and sepsis/septic shock (OR: 2.94, 95%CI (1.01-8.54)). CONCLUSIONS: In real life, Cefto-M is a safe antibiotic, comprising only half of prescriptions for respiratory infections, that is mainly administered as rescue therapy in pluripathological patients with severe infectious diseases.

Role of previous systemic antibiotic therapy on the probability of recurrence after an initial episode of Clostridioides difficile infection treated with vancomycin.

Objectives: To investigate the role of previous antibiotic therapy in the risk of recurrence after a Clostridioides difficile infection (CDI) treated with vancomycin. Methods: Multicentre observational study. Patients with a CDI episode achieving clinical cure with oral vancomycin and followed up 8 weeks were included. Previous antibiotic exposure up to 90 days was collected. Multivariate analysis of predictors of recurrence adjusted by the propensity score (PS) of being previously treated with each non-CDI antibiotic was performed. Results: Two hundred and forty-one patients were included; 216 (90%) had received systemic antibiotics. Fifty-three patients (22%) had a CDI recurrence. Rates of recurrence were lower in those treated with piperacillin/tazobactam in the last month when compared with those not receiving piperacillin/tazobactam [3 (7%) versus 50 (25%); P = 0.01], whereas higher rates were seen in those treated with cephalosporins in the last month [26/87 (30%) versus 27/154 (17%); P = 0.03]. In multivariate analysis controlled by the inverse probability of treatment weighting by PS, receiving ≥5 days of piperacillin/tazobactam in the last month as the last antibiotic regimen prior to CDI was independently associated with a lower risk of recurrence [adjusted OR (AOR) 0.13; 95% CI: 0.06-0.29; P < 0.0001] whereas exposure for ≥5 days to cephalosporins (versus piperacillin/tazobactam) was associated with an increased risk (AOR 10.9; 95% CI: 4.4-27.1; P < 0.0001). Conclusions: Recent use of piperacillin/tazobactam might be associated with a lower risk of CDI recurrence, while recent use of cephalosporins might promote an increased risk. These findings should be considered when treating hospitalized patients.

Impact of ceftazidime/avibactam versus best available therapy on mortality from infections caused by carbapenemase-producing Enterobacterales (CAVICOR study).

BACKGROUND: Infections caused by carbapenemase-producing Enterobacterales (CPE) are not well represented in pivotal trials with ceftazidime/avibactam. The best strategy for the treatment of these infections is unknown. METHODS: We conducted a multicentre retrospective observational study of patients who received ≥48 h of ceftazidime/avibactam or best available therapy (BAT) for documented CPE infections. The primary outcome was 30 day crude mortality. Secondary outcomes were 21 day clinical response and microbiological response. A multivariate logistic regression model was used to identify factors predictive of 30 day crude mortality. A propensity score to receive treatment with ceftazidime/avibactam was used as a covariate in the analysis. RESULTS: The cohort included 339 patients with CPE infections. Ceftazidime/avibactam treatment was used in 189 (55.8%) patients and 150 (44.2%) received BAT at a median of 2 days after diagnosis of infection. In multivariate analysis, ceftazidime/avibactam treatment was associated with survival (OR 0.41, 95% CI 0.20-0.80; P = 0.01), whereas INCREMENT-CPE scores of >7 points (OR 2.57, 95% CI 1.18-1.5.58; P = 0.01) and SOFA score (OR 1.20, 95% CI 1.08-1.34; P = 0.001) were associated with higher mortality. In patients with INCREMENT-CPE scores of >7 points, ceftazidime/avibactam treatment was associated with lower mortality compared with BAT (16/73, 21.9% versus 23/49, 46.9%; P = 0.004). Ceftazidime/avibactam was also an independent factor of 21 day clinical response (OR 2.43, 95% CI 1.16-5.12; P = 0.02) and microbiological eradication (OR 0.40, 95% CI 0.18-0.85; P = 0.02). CONCLUSIONS: Ceftazidime/avibactam is an effective alternative for the treatment of CPE infections, especially in patients with INCREMENT-CPE scores of >7 points. A randomized controlled trial should confirm these findings.

Characteristics and Management of Candidaemia Episodes in an Established Candida auris Outbreak.

The multi-resistant yeast Candida auris has become a global public health threat because of its ease to persist and spread in clinical environments, especially in intensive care units. One of the most severe manifestations of invasive candidiasis is candidaemia, whose epidemiology has evolved to more resistant non-albicansCandida species, such as C. auris. It is crucial to establish infection control policies in order to control an outbreak due to nosocomial pathogens, including the implementation of screening colonisation studies. We describe here our experience in managing a C. auris outbreak lasting more than two and a half years which, despite our efforts in establishing control measures and surveillance, is still ongoing. A total of 287 colonised patients and 47 blood stream infections (candidaemia) have been detected to date. The epidemiology of those patients with candidaemia and the susceptibility of C. auris isolates are also reported. Thirty-five patients with candidaemia (74.5%) were also previously colonised. Forty-three patients (91.5%) were hospitalised (61.7%) or had been hospitalised (29.8%) in the ICU before developing candidaemia. Antifungal therapy for candidaemia consisted of echinocandins in monotherapy or in combination with amphotericin B or isavuconazole. The most common underlying disease was abdominal surgery (29.8%). The thirty-day mortality rate was 23.4% and two cases of endophtalmitis due to C. auris were found. All isolates were resistant to fluconazole and susceptible to echinocandins and amphotericin B. One isolate became resistant to echinocandins two months after the first isolate. Although there are no established clinical breakpoints, minimum inhibitory concentrations for isavuconazole were low (≤ 1 µg/mL).

[Effect of lacosamide on the quality of life of patients with epilepsy]. / Efecto de la lacosamida sobre la calidad de vida del paciente con epilepsia.

INTRODUCTION: Epilepsy causes psychiatric disorders in 20-40% of patients impacting negatively on their quality of life. Lacosamide is a new antiepileptic as adjunctive therapy in partial seizures with or without generalization. AIM: We conducted a study to assess the impact of lacosamide as to the quality of life of epileptic patients. We used the HAD scale for anxiety and depression and QOLIE-10 scale for quality of life. We evaluated the efficacy and tolerability. PATIENTS AND METHODS: We collected prospectively poorly controlled epileptic patients are and added lacosamide treatment. Baseline visit, at 3 and 6 months were performed. The questionnaires are completed and the epilepsy information has been collected. RESULTS: 31 patients, age 45.5 ± 17.2 years, 64.5% males are included. Number of previous monthly crisis 1.6 ± 1.8. HAD anxiety scale shows a significant improvement at 3 and 6 months. HAD scale for depression reflects a significant improvement in quality parameters. QOLIE-10 shows significant improvement for the group with low quality of life after 3 and 6 months. After 6 months 61.3% of patients have a seizure reduction equal or more than 50% and 54.8% are seizure free. Dizziness is the most common side effect (22.8%). 74.2% continued treatment. CONCLUSIONS: Lacosamide may improve anxiety, depression and quality of life of epileptic patients regardless of seizure control. Response to treatment, adherence and side effects are similar to previous studies.

TITLE: Efecto de la lacosamida sobre la calidad de vida del paciente con epilepsia.Introduccion. La epilepsia provoca trastornos psiquiatricos en un 20-40% de los pacientes y repercute de forma negativa en su calidad de vida. La lacosamida es un nuevo antiepileptico que se utiliza como terapia añadida en crisis parciales con o sin generalizacion. Objetivo. Hemos realizado un estudio para valorar el impacto de la lacosamida en cuanto a la calidad de vida del paciente con epilepsia. Se han utilizado la escala hospitalaria de ansiedad y depresion (HADS) y la escala de calidad de vida en la epilepsia (QOLIE-10). Se ha valorado la eficacia y la tolerabilidad. Pacientes y metodos. Se recogen prospectivamente pacientes con epilepsia mal controlada y a los que se añade lacosamida. Se realiza una visita basal, a los tres y a los seis meses. Se cumplimentan los cuestionarios y se recaban los datos sobre la epilepsia. Resultados. Se incluyen 31 pacientes, con una edad media de 45,5 ± 17,2 años, un 64,5% varones. El numero de crisis mensuales previas es de 1,6 ± 1,8. La HADS para ansiedad muestra una mejoria significativa a los tres y seis meses. La HADS para depresion refleja una mejoria significativa en los parametros cualitativos. La QOLIE-10 muestra mejoria significativa para el grupo con baja calidad de vida previa a los tres y seis meses. Tras seis meses, el 61,3% de los pacientes presenta una reduccion de las crisis igual o superior al 50%, y el 54,8% esta libre de crisis. El mareo es el efecto secundario mas frecuente (22,8%). El 74,2% continua con el tratamiento. Conclusiones. La lacosamida podria mejorar la ansiedad, depresion y calidad de vida del paciente epileptico con independencia del control de las crisis. La respuesta al tratamiento, la adhesion y los efectos secundarios son similares a estudios previos.

[Menstrual headache: subtypes, clinical phenotypes and treatment]. / Cefalea menstrual: subtipos, fenotipos clinicos y tratamiento.

INTRODUCTION: Up to 60% of women relate their episodes of headache to menstrual cycle. Menstrual migraine has been included in the second edition of the International Classification of Headache disorders. Menstrual tension-type headache has not yet been recognised by the International Headache Society. AIMS: To evaluate the prevalence of different subtypes of menstrual headache and to analyze their clinical features and the treatment prescribed. PATIENTS AND METHODS: We prospectively included women attending several neurology outpatient clinics, from January to November 2008 whose headache appeared during the menstrual period. RESULTS: A total of 108 patients were included during the study period. Mean age was 34.8 ± 8.9 years-old. 29.3% suffered from pure menstrual migraine, 58.7% from menstrual related migraine, 4.5% from pure menstrual tension-type headache and 7.5% from menstrual related tension type headache. CONCLUSIONS: Our data suggest that menstrual related tension-type headaches exist with a prevalence found about 12%, in our neurology outpatient clinics.

[Aetiological analysis of 425 patients referred to an outpatient neurology service due to tremor or Parkinsonism]. / Análisis etiológico de 425 pacientes remitidos a una consulta extrahospitalaria de neurología por temblor o parkinsonismo.

INTRODUCTION: Movement disorders are a common reason for visits to outpatient neurology departments. This study has two objectives. The first is to analyse the diagnoses of patients referred to the neurology service due to tremor or Parkinsonism. The second aim is to analyse whether such patients are referred from primary care correctly or incorrectly. PATIENTS AND METHODS: The study examines patients referred from primary care to the neurology service in a medical specialty centre because of tremor or Parkinsonism. The final diagnoses established by the neurologist were analysed and patient referral was also analysed using a set of previously agreed criteria. RESULTS: The sample consisted of 425 consecutive patients who were referred from primary care due to tremor (n = 294) or Parkinsonism (n = 131). The most common diagnoses were Parkinson's disease (n = 211; 50%), essential tremor (n = 157; 37%) and pharmacological Parkinsonism (n = 23; 5%). Referral was considered to be incorrect in 39 patients and correct in 388 cases (91%). The causes of incorrect referrals were: pharmacological Parkinsonism (n = 23), anxiety that was not treated in primary care (n = 12) and hypothyroidism that went undiagnosed in primary care (n = 4). CONCLUSIONS: Parkinson's disease, essential tremor and pharmacological Parkinsonism are the most frequent diagnoses in patients who are referred from primary care because of tremor and Parkinsonism. Referral to a neurology service is correct in most cases, but there is still room for improvement.

Stroke with polyvascular atherothrombotic disease.

OBJECTIVE: To study the influence of polyvascular atherothrombotic disease on stroke patient prognosis, its relation with inflammatory markers, and to analyze the progression of atherothrombotic disease. METHODS: MITICO is a multi-centered prospective observational study recruiting non-anticoagulated ischemic stroke patients. Blood samples were obtained at baseline and at one year follow-up for determination of high sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), matrix metalloproteinase 9 (MMP-9), and cellular fibronectin (c-Fn). Patients with polyvascular atherothrombotic disease were considered when presented a history of angina-myocardial infarction, intermittent claudication or ischemic limbs-amputation at inclusion. RESULTS: The sample consisted of 863 patients, 121 of them considered as polyvascular atherothrombotic disease (14.02%). Recurrence and vascular death were higher in patients with polyvascular atherothrombotic disease, as compared to patients with monovascular atherothrombotic disease (19.8% vs. 12.4%, p=0.022). Baseline plasma levels of IL-6 and VCAM-1 were higher in patients with polyvascular atherothrombotic disease. IL-6 and VCAM-1 levels were independently associated with a new vascular episode/vascular death. This association was stronger in the group of patients with polyvascular atherothrombotic disease. Baseline levels of IL-6, VCAM-1 and c-Fn were significantly higher in patients who developed progression of atherothrombotic disease. The increase from baseline in MMP-9 and c-Fn levels after one year follow-up was associated to progression of atherothrombotic disease. CONCLUSIONS: Stroke patients with polyvascular atherothrombotic disease showed higher rates of vascular recurrence and a stronger association with inflammatory markers. Progression of atherothrombotic disease was associated with inflammatory markers.