RESUMO
OBJECTIVE: Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS). The most common clinical manifestations of MS are spasticity, pain, vesico-urethral disorders, cognitive impairments, chronic fatigue and sexual dysfunction. This review aims to explore the possible therapeutic options for managing sexual dysfunction in people with MS (PwMS). METHOD: A thorough search of the PubMed Medline database was performed. Records were limited to clinical studies published between 01/01/2010 up to 01/01/2022. The results were screened by the authors in pairs. RESULTS: The search identified 36 records. After screening, 9 records met the inclusion-exclusion criteria and were assessed. The pharmacological approaches investigated the effectiveness of sildenafil, tadalafil and onabotulinumtoxinA. Of the interventional studies the non-pharmacological investigated, the effectiveness of aquatic exercises, the application of pelvic floor exercises,the combination of pelvic floor exercises and mindfulness technique, the combination of pelvic floor exercises and electro muscular stimulation with electromyograph biofeedback, the application of yoga techniques and the efficacy of assistive devices like the clitoral vacuum suction device and the vibration device. CONCLUSION: The management of sexual dysfunction in PwMS needs to be further investigated. A team of healthcare professionals should be involved in the management of SD in order to address not only the primary (MS-related) SD symptoms but the secondary and tertiary as well. The main limitations that were identified in the existing literature were related to MS disease features, sample characteristics and evaluation tools and batteries.
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Esclerose Múltipla , Disfunções Sexuais Fisiológicas , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/terapia , Esclerose Múltipla/psicologia , Disfunções Sexuais Fisiológicas/terapia , Disfunções Sexuais Fisiológicas/complicações , Citrato de Sildenafila , Dor/complicações , Terapia por Exercício/métodosRESUMO
BACKGROUND: Fabry disease (FD) is an inherited lysosomal storage disorder, leading to multisystemic manifestations and causing significant morbidity and mortality. OBJECTIVE: The aim of this narrative review is to present the current and novel therapeutic strategies in FD, including symptomatic and specific treatment options. METHODS: A systematic literature search was conducted to identify relevant studies, including completed and ongoing randomized-controlled clinical trials (RCTs), prospective or retrospective cohort studies, case series and case reports that provided clinical data regarding FD treatment. RESULTS: A multidisciplinary symptomatic treatment is recommended for FD patients, personalized according to disease manifestations and their severity. During the last two decades, FD-specific treatments, including two enzyme-replacement-therapies (agalsidase alfa and agalsidase beta) and chaperone treatment with migalastat have been approved for use and allowed for symptoms' stabilization or even disease burden reduction. More therapeutic agents are currently under investigation. Substrate reduction therapies, including lucerastat and venglustat, have shown promising results in RCTs and may be used either as monotherapy or as complementary therapy to established enzymereplacement- therapies. More stable enzyme-replacement-therapy molecules that are associated with less adverse events and lower likelihood of neutralizing antibodies formation have also been developed. Ex-vivo and in-vivo gene therapy is being tested in animal models and pilot human clinical trials, with preliminary results showing a favorable safety and efficacy profile. CONCLUSION: The therapeutic landscape in FD appears to be actively expanding with more treatment options expected to become available in the near future, allowing for a more personalized approach in FD patients.
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Doença de Fabry , Animais , Humanos , Doença de Fabry/tratamento farmacológico , Doença de Fabry/etiologia , 1-Desoxinojirimicina/uso terapêutico , Terapia de Reposição de Enzimas/efeitos adversos , Terapia de Reposição de Enzimas/métodosRESUMO
OBJECTIVES: Stroke is the most common cause of disability in high-income countries. Several countries offer a limited range of advanced treatments with implications for outcomes, disability and costs. This study estimates the burden of disability that could have been avoided through the transition from traditional (no intravenous thrombolytic therapy (IVT), or endovascular thrombectomy (EVT)) to modern stroke treatments (treatment in stroke units, IVT and EVT). We perform a cost-effectiveness analysis comparing best practice with traditional stroke care, using Greece as a case study. MATERIALS AND METHODS: A Markov model was used to calculate costs and Quality Adjusted Life Years (QALYs) for each treatment strategy, using a lifetime horizon. Data for model inputs were derived from meta-analyses of trials, and national and international cost databases. Sensitivity analyses were also performed to address potential uncertainty and test the robustness of the findings. RESULTS: Incremental effectiveness comprised 0.22 QALYs per patient and year. Best practice was cost-effective for more than 90% of all iterations (ICER for the baseline scenario: 2,109.25/QALY). Sensitivity analysis demonstrated that the findings remain robust. Considering the stroke incidence in Greece, the annual additional cost to implement best practice was calculated to be between 0.07%-0.15% of the total health expenditure. CONCLUSION: Best practice stroke treatment was cost-effective and affordable in a case study based on Greece. The results could be leveraged by including effects of preventive policies and rehabilitation. They also highlight the importance of adopting modern treatment strategies from a cost-effectiveness perspective, apart from the improved clinical outcomes.
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Acidente Vascular Cerebral , Humanos , Análise Custo-Benefício , Grécia/epidemiologia , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia/métodos , Anos de Vida Ajustados por Qualidade de Vida , Fibrinolíticos/uso terapêuticoRESUMO
INTRODUCTION: Recent years have witnessed unprecedented progress in stroke care, but unmet needs persist regarding the efficacy of acute treatment and secondary prevention. Novel approaches are being tested to enhance the efficacy of thrombolysis or provide neuroprotection in non-thrombolized patients. AREAS COVERED: The current review highlights pharmaceutical agents under evaluation in clinical trials concerning the acute, subacute, and chronic phase post-stroke. We examine the evidence in favor of tenecteplase as an alternative thrombolytic drug to alteplase, nerinetide as a promising neuroprotective agent, and glibenclamide for reducing edema in malignant hemispheric infarction. We discuss the use of ticagrelor and the promising novel category of factor XI inhibitors in the subacute phase after stroke. We offer our insights on combined rivaroxaban and antiplatelet therapy, PCSK-9 inhibitors, and other non-statin hypolipidemic agents, as well as novel antidiabetic agents that have been shown to reduce cardiovascular events in the long-term. EXPERT OPINION: Current approaches in stroke treatment and stroke prevention have already transformed stroke care from a linear one-for-all treatment paradigm to a more individualized approach that targets specific patient subgroups with novel pharmaceutical agents. This tendency enriches the therapeutic armamentarium with novel agents developed for specific stroke subgroups. ABBREVIATIONS: IVT: intravenous thrombolysis; RCTs: randomized-controlled clinical trials; TNK: Tenecteplase; COVID-19: Coronavirus 2019 Disease; EXTEND-IA TNK: The Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke trial; AIS: acute ischemic stroke; NNT: number needed to treat; MT: mechanical thrombectomy; sICH: symptomatic intracranial hemorrhage; mRS: modified Rankin Scale; AHA/ASA: American Heart Association/American Stroke Association; ESO: European Stroke Organization; NA-1: Nerinetide; ENACT: Evaluating Neuroprotection in Aneurysm Coiling Therapy; CTA: CT angiography; TIA: transient ischemic attack; CHANCE: Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events; LOF: loss-of-function; PRINCE: Platelet Reactivity in Acute Nondisabling Cerebrovascular Events; THALES: Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA [acetylsalicylic acid] for Prevention of Stroke and Death; CHANCE-2: Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II; FXI: Factor XI; PACIFIC-STROKE: Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334-NonCardioembolic Stroke study; COMPASS: Cardiovascular Outcomes for People Using Anticoagulation Strategies; CANTOS-ICAD: Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease; SAMMPRIS: Stenting and Aggressive Medical Therapy for Preventing Recurrent Stroke in Intracranial Stenosis; WASID: Warfarin-Aspirin Symptomatic Intracranial Disease; SPARCL: Stroke Prevention by Aggressive Reduction in Cholesterol Levels; LDL-C: low-density lipoprotein cholesterol; TST: Treat Stroke to Target; IMPROVE-IT: Improved Reduction of Outcomes: Vytorin Efficacy International Trial; PCSK9: proprotein convertase subtilisin-kexin type 9; FOURIER: Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; CLEAR: Cholesterol Lowering via Bempedoic acid, an ACL-inhibiting Regimen; REDUCE-IT: Reduction of Cardiovascular Events With EPA Intervention Trial; STRENGTH: Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia; ACCORD: Action to Control Cardiovascular Risk in Diabetes; ADVANCE: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; VADT: Veterans Affairs Diabetes Trial; GLP-1R: Glucagon-like peptide-1 receptor; SGLT2: sodium-glucose cotransporter 2; CONVINCE: COlchicine for preventioN of Vascular Inflammation in Non-CardioEmbolic stroke; PROBE: Prospective Randomized Open-label Blinded Endpoint assessment.
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Anticolesterolemiantes/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Ensaios Clínicos como Assunto/métodos , Fibrinolíticos/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Isquemia Encefálica/sangue , Isquemia Encefálica/epidemiologia , Fator XI/antagonistas & inibidores , Fator XI/metabolismo , Humanos , Inibidores de PCSK9 , Pró-Proteína Convertase 9/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. METHODS AND RESULTS: Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA2DS2-VASc score >4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke. CONCLUSIONS: In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Isquemia Encefálica/prevenção & controle , Hemorragia/epidemiologia , Vitamina K/antagonistas & inibidores , Doença Aguda , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Recidiva , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Current recommendations advocate that pretreatment with intravenous thrombolysis (IVT) should first be offered to all eligible patients with emergent large vessel occlusion (ELVO) before an endovascular thrombectomy (ET) procedure. However, there are observational data that question the safety and efficacy of IVT pretreatment in patients with ELVO. METHODS: We performed a meta-analysis of the included subgroups from ET randomized controlled trials (RCTs) to evaluate the comparative efficacy between direct ET without IVT pretreatment and bridging therapy (IVT and ET) in patients with ELVO. RESULTS: We included a total of seven RCTs, including 1764 patients with ELVO (52.8% men). Patients receiving bridging therapy (IVT followed by ET) had lower rates (p = 0.041) of 90-day death/severe dependency (modified Rankin Scale-score of 5-6; 19.0%, 95% CI: 14.1-25.1%) compared with patients receiving only ET (31.0%, 95% CI: 21.2-42.9%). Moreover, patients receiving IVT and ET had a nonsignificant (p = 0.389) trend towards higher 90-day functional independence rates (51.4%, 95% CI: 42.5-60.1%) compared with patients undergoing only ET (41.7%, 95% CI: 24.1-61.7%). Finally, shift-analysis uncovered a nonsignificant trend towards functional improvement at 90 days for bridging therapy over ET (cOR = 1.28, 95% CI: 0.91-1.89; p = 0.155). It should be noted that patients included in the present meta-analysis were not randomized to receive IVT, and thus the two groups (bridging therapy versus ET monotherapy) may differ in terms of baseline characteristics and, in particular, in terms of onset to groin puncture time and thus the risk of confounding bias cannot be ruled out. CONCLUSION: Despite the limitations and the risk of confounding bias, our findings contradict the recent notion regarding potential equality between ET and bridging therapy in ELVO patients and suggest that IVT and ET are complementary therapies that should be pursued in a parallel and noncompeting fashion.
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Dissecção Aórtica/diagnóstico por imagem , Artéria Basilar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Aneurisma Intracraniano/diagnóstico por imagem , Dissecção Aórtica/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Aneurisma Intracraniano/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Yin-YangRESUMO
BACKGROUND: Psychological stress is common to patients submitted to cardiovascular operations. The purpose of this pilot, single-center, open-label, randomized controlled trial was to investigate the effects of a stress management program (SMP) on patients undergoing carotid endarterectomy (CEA). METHODS: A sample of 24 patients with significant (>70%) carotid stenosis was finally randomized to SMP (intervention group; n = 12) or no-stress management intervention (control group; n = 12) before CEA. SMP consisted of 2 relaxation techniques (relaxation-breathing and guided imagery) before and 8 weeks after CEA. Measurements included Perceived Stress Scale (PSS), Hospital Anxiety and Depression Scale (HADS), Health Locus of Control Scale (HLC), and blood pressure and heart rate. RESULTS: The 2 groups did not differ in terms of demographic characteristics, vascular risk factors, and baseline psychometric measurements. No delay on the time of surgery was caused by the practice of the relaxation techniques. Both perceived stress and anxiety improved within the intervention group at the end of the program (P = 0.005 and P = 0.007, respectively). No improvement in PSS-14, HLC, and HADS scores were documented in control group at the end of the 8-week follow-up period. The intervention group had lower PSS-14 scores at 8 weeks after CEA (median PSS-14 score, 20 points; range, 10-28) compared with control group (median PSS, 25 points; range, 11-47; P = 0.026). No significant effect of SMP was found for blood pressure and heart rate measurements. CONCLUSIONS: Our results indicate that relaxation techniques appear to be beneficial in terms of stress and anxiety reduction in patients undergoing CEA. These findings require independent confirmation in the setting of a larger, double-blind randomized controlled trial.
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Exercícios Respiratórios , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Imagens, Psicoterapia , Terapia de Relaxamento/métodos , Estresse Psicológico/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Ansiedade/prevenção & controle , Ansiedade/psicologia , Exercícios Respiratórios/efeitos adversos , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/psicologia , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/psicologia , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Escalas de Graduação Psiquiátrica , Psicometria , Terapia de Relaxamento/efeitos adversos , Fatores de Risco , Estresse Psicológico/diagnóstico , Estresse Psicológico/psicologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Based upon scarce clinical data in humans and experimental findings in animal studies, it has been postulated that the ascending gustatory projection from the nucleus tractus solitarii courses ipsilaterally through the pons and midbrain to the ipsilateral ventral posteromedial nucleus. Thus, it has been assumed that ischemic lesions affecting the secondary projection gustatory fibers would cause ipsilateral taste disorders. DESCRIPTION OF CASE: We report a case of bilateral ageusia following an acute right midbrain and thalamic infarction affecting the ipsilateral central trigeminal tract and ventral posteromedial nucleus in a right-handed man. CONCLUSION: The present case indicates that, in contrast to animal data, some secondary projection gustatory fibers may cross in humans and consequently unilateral right-sided posterior circulation ischemic lesions can cause bilateral gustatory deficits.