Pharmacotherapy and non-invasive neuromodulation for neuropathic pain:a systematic review and meta-analysis

Background: There remains a substantial unmet need for effective and safe treatments for neuropathic pain. The Neuropathic Pain Special Interest Group aimed to update treatment recommendations, published in 2015, on the basis of new evidence from randomised controlled trials, emerging neuromodulation techniques, and advances in evidence synthesis. Methods: For this systematic review and meta-analysis, we searched Embase, PubMed, the International Clinical Trials Registry, and ClinicalTrials.gov from data inception for neuromodulation trials and from Jan 1, 2013, for pharmacological interventions until Feb 12, 2024. We included double-blind, randomised, placebo-controlled trials that evaluated pharmacological and neuromodulation treatments administered for at least 3 weeks, or if there was at least 3 weeks of follow-up, and which included at least ten participants per group. Trials included participants of any age with neuropathic pain, defined by the International Association for the Study of Pain. We excluded trials with enriched enrolment randomised withdrawal designs and those with participants with mixed aetiologies (ie, neuropathic and non-neuropathic pain) and conditions such as complex regional pain syndrome, low back pain without radicular pain, fibromyalgia, and idiopathic orofacial pain. We extracted summary data in duplicate from published reports, with discrepancies reconciled by a third independent reviewer on the platform Covidence. The primary efficacy outcome was the proportion of responders (50% or 30% reduction in baseline pain intensity or moderate pain relief). The primary safety outcome was the number of participants who withdrew from the treatment owing to adverse events. We calculated a risk difference for each comparison and did a random-effects meta-analysis. Risk differences were used to calculate the number needed to treat (NNT) and the number needed to harm (NNH) for each treatment. Risk of bias was assessed by use of the Cochrane risk of bias tool 2 and certainty of evidence assessed by use of GRADE. Recommendations were based on evidence of efficacy, adverse events, accessibility, and cost, and feedback from engaged lived experience partners. This study is registered on PROSPERO, CRD42023389375. Findings: We identified 313 trials (284 pharmacological and 29 neuromodulation studies) for inclusion in the meta-analysis. Across all studies, 48 789 adult participants were randomly assigned to trial groups (20 611 female and 25 078 male participants, where sex was reported). Estimates for the primary efficacy and safety outcomes were tricyclic antidepressants (TCAs) NNT=4·6 (95% CI 3·2–7·7), NNH=17·1 (11·4–33·6; moderate certainty of evidence), α2δ-ligands NNT=8·9 (7·4–11·10), NNH=26·2 (20·4–36·5; moderate certainty of evidence), serotonin and norepinephrine reuptake inhibitors (SNRIs) NNT=7·4 (5·6–10·9), NNH=13·9 (10·9–19·0; moderate certainty of evidence), botulinum toxin (BTX-A) NNT=2·7 (1·8–9·61), NNH=216·3 (23·5–∞; moderate certainty of evidence), capsaicin 8% patches NNT=13·2 (7·6–50·8), NNH=1129·3 (135·7–∞; moderate certainty of evidence), opioids NNT=5·9 (4·1–10·7), NNH=15·4 (10·8–24·0; low certainty of evidence), repetitive transcranial magnetic stimulation (rTMS) NNT=4·2 (2·3–28·3), NNH=651·6 (34·7–∞; low certainty of evidence), capsaicin cream NNT=6·1 (3·1–∞), NNH=18·6 (10·6–77·1; very low certainty of evidence), lidocaine 5% plasters NNT=14·5 (7·8–108·2), NNH=178·0 (23·9–∞; very low certainty of evidence). The findings provided the basis for a strong recommendation for use of TCAs, α2δ-ligands, and SNRIs as first-line treatments; a weak recommendation for capsaicin 8% patches, capsaicin cream, and lidocaine 5% plasters as second-line recommendation; and a weak recommendation for BTX-A, rTMS, and opioids as third-line treatments for neuropathic pain. Interpretation: Our results support a revision of the Neuropathic Pain Special Interest Group recommendations for the treatment of neuropathic pain. Treatment outcomes are modest and for some treatments uncertainty remains. Further large placebo-controlled or sham-controlled trials done over clinically relevant timeframes are needed. Funding: NeuPSIG and ERA-NET Neuron.</p

Relapses in Patients Treated with High-Dose Biotin for Progressive Multiple Sclerosis

High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Several reports have suggested that HDB treatment may be associated with an increased risk of relapse. We aimed to determine whether HDB increases the risk of clinical relapse in PMS and describe the characteristics of the patients who experience it. We conducted a French, multicenter, retrospective study, comparing a group of PMS patients treated with HDB to a matched control group. Poisson regression was applied to model the specific statistical distribution of the annualized relapse rate (ARR). A propensity score (PS), based on the inverse probability of treatment weighting (IPTW), was used to adjust for indication bias and included the following variables: gender, primary PMS or not, age, EDSS, time since the last relapse, and co-prescription of a DMT. Two thousand six hundred twenty-eight patients treated with HDB and 654 controls were analyzed with a follow-up of 17 ± 8 months. Among them, 148 validated relapses were observed in the group treated with biotin and 38 in the control group (p = 0.62). After adjustment based on the PS, the ARR was 0.044 ± 0.23 for the biotin-treated group and 0.028 ± 0.16 for the control group (p = 0.18). The more relapses there were before biotin, the higher the risk of relapse during treatment, independently from the use of HDB. While the number of relapses reported for patients with no previous inflammatory activity receiving biotin has gradually increased, the present retrospective study is adequately powered to exclude an elevated risk of relapse for patients with PMS treated with HDB.Observatoire Français de la Sclérose en Plaque

The Distressed Brain: A Group Blind Source Separation Analysis on Tinnitus

Background: Tinnitus, the perception of a sound without an external sound source, can lead to variable amounts of distress. Methodology: In a group of tinnitus patients with variable amounts of tinnitus related distress, as measured by the Tinnitus Questionnaire (TQ), an electroencephalography (EEG) is performed, evaluating the patients ’ resting state electrical brain activity. This resting state electrical activity is compared with a control group and between patients with low (N = 30) and high distress (N = 25). The groups are homogeneous for tinnitus type, tinnitus duration or tinnitus laterality. A group blind source separation (BSS) analysis is performed using a large normative sample (N = 84), generating seven normative components to which high and low tinnitus patients are compared. A correlation analysis of the obtained normative components ’ relative power and distress is performed. Furthermore, the functional connectivity as reflected by lagged phase synchronization is analyzed between the brain areas defined by the components. Finally, a group BSS analysis on the Tinnitus group as a whole is performed. Conclusions: Tinnitus can be characterized by at least four BSS components, two of which are posterior cingulate based, one based on the subgenual anterior cingulate and one based on the parahippocampus. Only the subgenual component correlates with distress. When performed on a normative sample, group BSS reveals that distress is characterized by two anterior cingulate based components. Spectral analysis of these components demonstrates that distress in tinnitus is relate

Identifying Maternal Conditions Leading to Gabapentinoid Prescriptions in Pregnancy Using Electronic Health Records from Six European Countries: A Contribution from the IMI ConcePTION Project

Introduction and Objective Given the recent increase in the prescription and dispensation of gabapentinoids (gabapentin and pregabalin) and the importance of controlling for underlying maternal illnesses in drug safety studies, we aimed to develop algorithms for identifying maternal conditions leading to gabapentinoid prescribing among pregnant women using data from six electronic healthcare data sources across Europe. Methods The study was conducted in Finland, France (Haute-Garonne), Italy (Emilia Romagna), Norway, Spain (Valencian region), and Wales (UK), covering three million pregnancies from 2006 to 2020. Algorithms were developed to detect epilepsy, neuropathic pain, and generalized anxiety disorder (GAD) (approved indications for gabapentinoids by the European Medicines Agency, with the exception of gabapentin for GAD) using data ± 1 year around the gabapentinoid prescription date. Data included prescriber specialty, primary and specialized health care diagnoses, and co-prescription/dispensation data. Additional analyses investigated potential unlicensed indications (such as fibromyalgia, restless legs syndrome, bipolar disorder) and potential for abuse (using codes for substance use disorders and alcohol withdrawal). Results Gabapentinoids were prescribed/dispensed in 1770 pregnancies (7.7 per 1000) in Spain, 2912 pregnancies (6.6 per 1000) in Wales, 3163 pregnancies (3.6 per 1000) in Norway, 2406 pregnancies (3.0 per 1000) in Finland, 908 pregnancies (2.2 per 1000) in Italy, and 269 pregnancies (1.9 per 1000) in France. A maternal condition related to gabapentinoid prescriptions was identified by the algorithm in 2797 (88.4%) in Norway, 2180 (74.9%) in Wales, 1269 (71.7%) in Spain, 1534 (63.8%) in Finland, 163 (60.6%) in France, and 396 (43.6%) pregnancies in Italy. Anxiety (licensed or unlicensed) was the most commonly captured condition in Wales (70.5%), Spain (51.5%), Finland (42.0%), and Italy (26.2%), whereas neuropathic pain prevailed in Norway (76.9%) and France (49.8%). Epilepsy was the least frequent maternal condition leading to gabapentinoid prescriptions across all data sources (below 15% of all pregnancies). The relative preponderance of these conditions differed between pregabalin and gabapentin. Additionally, unlicensed indications were captured in 0% to 13% of pregnancies, depending on the data source. The analyses of potential for abuse showed that records of alcohol withdrawal and/or substance use disorders (within 1 year before and after the gabapentinoids prescription/dispensation date) were present in 3% of pregnancies in Italy and up to 23% in Wales. Conclusions Our study provides valuable insights into gabapentinoid use during pregnancy, with anxiety being the most common condition among pregnant women with gabapentinoid prescriptions in Finland, Italy, Spain, and Wales, whereas neuropathic pain predominated in France and Norway. Moreover, we found that between 3 and 23% of these pregnancies were associated with substance abuse, underscoring the need for careful prescribing of commonly abused medicines. The proposed methods for detecting maternal conditions leading to prescribing will facilitate accurate assessment of medication use and safety during pregnancy, whilst addressing confounding by indication

Proyecto, investigación e innovación en urbanismo, arquitectura y diseño industrial

Actas de congresoLas VII Jornadas de Investigación “Encuentro y Reflexión” y I Jornadas de Investigación de becarios y doctorandos. Proyecto, investigación e innovación en Urbanismo, Arquitectura y Diseño Industrial se centraron en cuatro ejes: el proyecto; la dimensión tecnológica y la gestión; la dimensión social y cultural y la enseñanza en Arquitectura, Urbanismo y Diseño Industrial, sustentados en las líneas prioritarias de investigación definidas epistemológicamente en el Consejo Asesor de Ciencia y Tecnología de esta Universidad Nacional de Córdoba. Con el objetivo de afianzar continuidad, formación y transferencia de métodos, metodología y recursos se incorporó becarios y doctorandos de los Institutos de investigación. La Comisión Honoraria la integraron las tres Secretarias de Investigación de la Facultad, arquitectas Marta Polo, quien fundó y María del Carmen Franchello y Nora Gutiérrez Crespo quienes continuaron la tradición de la buena práctica del debate en la cotidianeidad de la propia Facultad. Los textos que conforman las VII Jornadas son los avances y resultados de las investigaciones realizadas en el bienio 2016-2018.Fil: Novello, María Alejandra. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Repiso, Luciana. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Mir, Guillermo. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Brizuela, Natalia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Herrera, Fernanda. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Períes, Lucas. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Romo, Claudia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Gordillo, Natalia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Andrade, Elena Beatriz. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; Argentin