RESUMEN
BACKGROUND: The recreational use of nitrous oxide (N2O) has increased in recent years with a noticeable surge in the incidence of nitrous oxide-related myeloneuropathy. OBJECTIVES: To raise awareness of increasing myeloneuropathy due to recreational nitrous oxide misuse in Israel. METHODS: We conducted a case series documenting the clinical and investigative features of eight patients presenting with nitrous oxide-induced myeloneuropathy who were admitted to our departments. RESULTS: Paresthesia was the chief complaint in all patients, with sensory gait ataxia being a common feature, which was often accompanied by Romberg's sign and mild lower limb weakness. Vitamin B12 levels were below the normal range in seven patients, accompanied by elevated homocysteine and methylmalonic acid levels. Magnetic resonance imaging scans revealed hyperintense signals in the dorsal columns of the cervical spine. All patients improved following vitamin B12 injections. CONCLUSIONS: Enhancing awareness, prompting the use of appropriate investigations, and advocating for timely treatment are needed to overcome the risks associated with nitrous oxide misuse.
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Imagen por Resonancia Magnética , Óxido Nitroso , Vitamina B 12 , Humanos , Óxido Nitroso/efectos adversos , Óxido Nitroso/administración & dosificación , Masculino , Adulto , Vitamina B 12/administración & dosificación , Femenino , Israel/epidemiología , Imagen por Resonancia Magnética/métodos , Enfermedades de la Médula Espinal/inducido químicamente , Parestesia/inducido químicamente , Parestesia/diagnóstico , Persona de Mediana Edad , Uso Recreativo de Drogas , Ataxia de la Marcha/inducido químicamente , Ataxia de la Marcha/etiología , Adulto Joven , Trastornos Relacionados con Sustancias/complicaciones , Deficiencia de Vitamina B 12/inducido químicamente , Deficiencia de Vitamina B 12/diagnósticoRESUMEN
OBJECTIVE: This analysis of the first-line cohort of LASER201 study evaluated the efficacy and safety of lazertinib 240 mg as a frontline therapy for epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: A total of 43 patients, with EGFR mutation-positive (Exon19Del, n = 24; L858R, n = 18; G719X, n = 1) locally advanced or metastatic NSCLC who had not previously received EGFR tyrosine kinase inhibitor (EGFR TKI) therapy, received once-daily lazertinib 240 mg. EGFR mutation status was confirmed by local or central testing. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review. Secondary efficacy endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), tumor shrinkage, and overall survival (OS). RESULTS: At the primary data cut-off (DCO; January 8, 2021), the ORR was 70 % (95 % confidence interval [CI]: 56.0-83.5), DCR was 86 % (95 % CI: 75.7-96.4) and the median DoR was 23.5 (95 % CI: 12.5-not reached) months. The median PFS was 24.6 (95 % CI: 12.2-30.2) months. At the final DCO (March 30, 2023), the median OS was not estimable and the median follow-up duration for OS was 55.2 [95 % CI: 22.8-55.7] months. OS rates at 36 months and 54 months were 66 % (95 % CI: 47.5-79.3 %) and 55 % (95 % CI: 36.6-70.7 %), respectively. The most commonly reported TEAEs were rash (54 %), diarrhea (47 %), pruritus (35 %), and paresthesia (35 %). No drug-related rash or pruritus TEAEs of grade 3 or higher were reported. Diarrhea and paresthesia of grade 3 or higher were reported in 3 (7 %) and 1 (2 %) patients, respectively. CONCLUSION: This analysis demonstrated long-term clinical benefit with lazertinib 240 mg in patients with EGFR-mutated NSCLC who had not previously received EGFR TKIs. The safety profile for lazertinib was tolerable and consistent with that previously reported.
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Carcinoma de Pulmón de Células no Pequeñas , Exantema , Neoplasias Pulmonares , Morfolinas , Pirazoles , Pirimidinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Estudios de Seguimiento , Parestesia/inducido químicamente , Parestesia/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Receptores ErbB/genética , Diarrea/inducido químicamente , Exantema/inducido químicamente , Prurito/tratamiento farmacológico , MutaciónRESUMEN
BACKGROUND: Most oncologic patients receiving chemotherapy suffer from neuropathy, which not only severely affects quality of life but also may lead to chemotherapy dose reductions or even discontinuation of cancer therapy. Still, it is difficult to sufficiently control these symptoms with the currently available pharmacological treatments. High tone therapy was reported to be an effective option for neuropathies due to different etiologies. However, to date, there are no studies on high tone therapy in patients with chemotherapy-induced peripheral neuropathy. METHODS: This randomized, double-blind, and placebo-controlled two-center study was conducted at the Departments of Physical and Rehabilitation Medicine at the Clinics Donaustadt and Ottakring, Vienna, Austria. Patients with histologically verified colorectal carcinoma treated with a platin derivate and neuropathic symptoms were invited to participate. High tone therapy took place in a home-based setting using the HiToP 191 PNP ® or placebo device for three weeks. Neuropathic symptoms and quality of life were assessed via questionnaires. After the follow-up examination, an opt-in was offered to the patients in the placebo group in terms of an open-label treatment with a verum HiToP PNP ® device. In addition, patients with chemotherapy-induced peripheral neuropathy due to various malignant diseases were treated in an open-label setting reflecting a clinical application observation. These patients are reported as a separate group. RESULTS: In the verum group, there was a significant reduction of paresthesias and mental stress due to paresthesias from baseline until end of therapy, compared to placebo. These findings were observed in the opt-in subgroup, as well. In the open-label clinical application observation group, intensity and mental stress due to paresthesia, pain, cramps, and intensity of tightness/pressure were significantly lower at the end of therapy, compared to baseline. CONCLUSIONS: Home-based high tone therapy brought about a significant alleviation in paresthesias and mental stress due to paresthesias in the verum but not the placebo group. In the clinical application observation, a significant alleviation in several further neuropathic symptoms was seen. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov (NCT06048471, 03/02/2020).
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Antineoplásicos , Neoplasias Colorrectales , Enfermedades del Sistema Nervioso Periférico , Humanos , Calidad de Vida , Proyectos Piloto , Parestesia/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/terapia , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Antineoplásicos/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Método Doble CiegoRESUMEN
Subacute combined degeneration (SCD) is an acquired neurologic complication from prolonged vitamin B12 deficiency. As a result of dorsal and lateral spinal cord column degeneration, patients present with a range of neurological symptoms, including paresthesias, ataxia, and muscle weakness. Without prompt treatment, irreversible nerve damage occurs. Here we present a young man who developed progressive ascending paresthesias and lower extremity weakness after escalated nitrous oxide use. This case highlights the importance of considering SCD from nitrous oxide toxicity when patients present with progressive ataxia, paresthesia, and lower extremity weakness.
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Enfermedades de la Médula Espinal , Degeneración Combinada Subaguda , Deficiencia de Vitamina B 12 , Masculino , Humanos , Óxido Nitroso/efectos adversos , Parestesia/inducido químicamente , Parestesia/complicaciones , Vitamina B 12/uso terapéutico , Deficiencia de Vitamina B 12/inducido químicamente , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/diagnóstico , Degeneración Combinada Subaguda/complicaciones , Enfermedades de la Médula Espinal/complicaciones , Ataxia/complicacionesRESUMEN
AIM: The aim of this systematic review is to accumulate the available evidence on management approaches as well as factors resulting in the development of paresthesia due to sealer extrusion. MATERIALS AND METHODS: A literature search was conducted in MEDLINE, EMBASE, and Web of Science and Cochrane Central Register of Controlled Trials up to March 2022, accompanied by a manual search of journals, textbooks, and grey literature. Inclusion criteria were studies on adult patients experiencing paresthesia related to sealer extrusion. The quality of included studies was appraised using a custom set of criteria. RESULTS: A total of 102 publications were identified, and 9 of them fulfilled the inclusion criteria. All of the included studies were case reports describing a total of 10 patients. The predetermined data were independently extracted and evaluated by four reviewers. CONCLUSION: Because of the low amount and quality of available evidence, conclusions on the factors resulting in paresthesia due to sealer extrusion cannot be drawn. The management approach remains empirical. The need for prospective studies is highlighted. The future case reports in endodontics ought to be reported in a uniform and methodological way. CLINICAL SIGNIFICANCE: Paresthesia as a result of endodontic sealer extrusion is an alarming complication of endodontic treatment that general dentists need to be aware of. Although worrying, for both clinician and patient, it is a manageable complication and early diagnosis is important; thus, dentists need to be educated on this topic.
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Endodoncia , Materiales de Obturación del Conducto Radicular , Adulto , Humanos , Parestesia/inducido químicamente , Estudios Prospectivos , Materiales de Obturación del Conducto Radicular/efectos adversosRESUMEN
BACKGROUND: This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with drug-resistant epilepsy. VNS consists of chronic, intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator. OBJECTIVES: To evaluate the efficacy and tolerability of VNS when used as add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For this update, we searched the Cochrane Register of Studies (CRS), and MEDLINE Ovid on 3 March 2022. We imposed no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from the Specialised Registers of Cochrane Review Groups, including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. SELECTION CRITERIA: We considered parallel or cross-over, randomised, double-blind, controlled trials of VNS as add-on treatment, which compared high- and low-level stimulation (including three different stimulation paradigms: rapid, mild, and slow duty-cycle), and VNS stimulation versus no stimulation, or a different intervention. We considered adults or children with drug-resistant focal seizures who were either not eligible for surgery, or who had failed surgery. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods, assessing the following outcomes: 1. 50% or greater reduction in seizure frequency 2. Treatment withdrawal (any reason) 3. Adverse effects 4. Quality of life (QoL) 5. Cognition 6. Mood MAIN RESULTS: We did not identify any new studies for this update, therefore, the conclusions are unchanged. We included the five randomised controlled trials (RCT) from the last update, with a total of 439 participants. The baseline phase ranged from 4 to 12 weeks, and double-blind treatment phases from 12 to 20 weeks. We rated two studies at an overall low risk of bias, and three at an overall unclear risk of bias, due to lack of reported information about study design. Effective blinding of studies of VNS is difficult, due to the frequency of stimulation-related side effects, such as voice alteration. The risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.73 (95% confidence interval (CI) 1.13 to 2.64; 4 RCTs, 373 participants; moderate-certainty evidence), showing that high frequency VNS was over one and a half times more effective than low frequency VNS. The RR for treatment withdrawal was 2.56 (95% CI 0.51 to 12.71; 4 RCTs, 375 participants; low-certainty evidence). Results for the top five reported adverse events were: hoarseness RR 2.17 (99% CI 1.49 to 3.17; 3 RCTs, 330 participants; moderate-certainty evidence); cough RR 1.09 (99% CI 0.74 to 1.62; 3 RCTs, 334 participants; moderate-certainty evidence); dyspnoea RR 2.45 (99% CI 1.07 to 5.60; 3 RCTs, 312 participants; low-certainty evidence); pain RR 1.01 (99% CI 0.60 to 1.68; 2 RCTs; 312 participants; moderate-certainty evidence); paraesthesia 0.78 (99% CI 0.39 to 1.53; 2 RCTs, 312 participants; moderate-certainty evidence). Results from two studies (312 participants) showed that a small number of favourable QOL effects were associated with VNS stimulation, but results were inconclusive between high- and low-level stimulation groups. One study (198 participants) found inconclusive results between high- and low-level stimulation for cognition on all measures used. One study (114 participants) found the majority of participants showed an improvement in mood on the Montgomery-Åsberg Depression Rating Scale compared to baseline, but results between high- and low-level stimulation were inconclusive. We found no important heterogeneity between studies for any of the outcomes. AUTHORS' CONCLUSIONS: VNS for focal seizures appears to be an effective and well-tolerated treatment. Results of the overall efficacy analysis show that high-level stimulation reduced the frequency of seizures better than low-level stimulation. There were very few withdrawals, which suggests that VNS is well tolerated. Adverse effects associated with implantation and stimulation were primarily hoarseness, cough, dyspnoea, pain, paraesthesia, nausea, and headache, with hoarseness and dyspnoea more likely to occur with high-level stimulation than low-level stimulation. However, the evidence for these outcomes is limited, and of moderate to low certainty. Further high-quality research is needed to fully evaluate the efficacy and tolerability of VNS for drug-resistant focal seizures.
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Epilepsia Refractaria , Estimulación del Nervio Vago , Adulto , Anticonvulsivantes/uso terapéutico , Niño , Tos , Epilepsia Refractaria/tratamiento farmacológico , Quimioterapia Combinada , Disnea/tratamiento farmacológico , Ronquera/inducido químicamente , Ronquera/tratamiento farmacológico , Humanos , Dolor/tratamiento farmacológico , Parestesia/inducido químicamente , Convulsiones/tratamiento farmacológico , Estimulación del Nervio Vago/efectos adversosRESUMEN
Although many materials are used for root canal fillings in endodontic treatment, calcium hydroxide has been preferred for many years due to its bactericidal effect and biocompatibility. Calcium hydroxide can be applied in more than one form. In this case study, calcium hydroxide in viscous form, applied into the root canal during endodontic treatment, overflowed from the apical part of the tooth to the inferior alveolar nerve canal. Postoperative paraesthesia was observed in the patient. Dental volumetric tomography was performed to study the extent of sealer in the inferior alveolar nerve canal. Considering the short resorption time of the calcium hydroxide paste, no surgical intervention was performed on the patient. After 6 months, the root canal material was completely resorbed, and paraesthesia decreased. At the 3-year follow-up, the patient's paraesthesia had completely disappeared.
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Hidróxido de Calcio , Materiales de Obturación del Conducto Radicular , Hidróxido de Calcio/efectos adversos , Humanos , Nervio Mandibular/cirugía , Parestesia/inducido químicamente , Materiales de Obturación del Conducto Radicular/efectos adversos , Obturación del Conducto Radicular/efectos adversosRESUMEN
BACKGROUND: Several neurologic complications have been reported in close temporal association with both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and following vaccination against SARS-CoV-2. Specifically, several cases of Guillain-Barré syndrome (GBS) have been reported in temporal relationship with COVID-19 vaccination, with two small case series describing a specific phenotype with bifacial weakness and paresthesia in the limbs. METHODS: We retrospectively collected patients who developed a new-onset neuromuscular disorder in the first 6 weeks after receiving a COVID-19 vaccine (either first or second dose). The patients were collected from one tertiary care centre and one secondary care centre from February to July 2021. RESULTS: We report eight patients who developed phenotypically diverse neuromuscular disorders in the weeks following COVID-19 vaccination, with a presumed immune-mediated etiology. In our case series, we report three patients with classical GBS, one patient with bifacial weakness with paresthesia variant of GBS, two patients with subacute-onset chronic inflammatory demyelinating polyneuropathy (CIDP), one patient with brachial plexopathy and one patient with subacute axonal sensorimotor polyneuropathy. CONCLUSIONS: New-onset neuromuscular disorders with onset in the weeks after COVID-19 vaccination can include diverse phenotypes. A causal relationship between these disorders and the vaccine cannot be proven at present, and further epidemiological studies are needed to further investigate this association.
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Vacunas contra la COVID-19 , COVID-19 , Síndrome de Guillain-Barré , COVID-19/complicaciones , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Síndrome de Guillain-Barré/inducido químicamente , Humanos , Parestesia/inducido químicamente , Estudios Retrospectivos , SARS-CoV-2 , Vacunación/efectos adversosRESUMEN
INTRODUCTION: Oxaliplatin is a platinum containing alkylating agent commonly used in the management of colorectal cancers. The most common dose-limiting toxicity of oxaliplatin is peripheral neuropathy, which can be severe enough to cause treatment discontinuation. We present a case of dysarthria and laryngopharyngeal dysesthesia (LPD) that developed during the first dose of oxaliplatin, which showed dose-dependent reduction in severity in subsequent cycles. CASE REPORT: A 52-year-old female patient with adenocarcinoma of rectum (pT4N2M0) was prescribed oxaliplatin (130â mg/m2) and capecitabine(2000mg/m2). She developed heaviness in the tongue, slurred speech, jaw pain, perioral paresthesia within 30â min after the end of 3â h infusion of oxaliplatin in the first cycle. The symptoms subsided without any sequelae in two days. However, in the subsequent cycles as the dose of the oxaliplatin was reduced, similar symptoms reappeared but were of reduced in severity. No dysesthesia symptoms were observed in the 4th cycle when the oxaliplatin was administered at 85â mg/m2. MANAGEMENT AND OUTCOME: As and when the patient developed symptoms - slurred speech, jaw pain during the first three cycles, she was managed with inj. Hydrocortisone (100â mg i.v.) and one ampoule of pheniramine (45â mg i.v.). DISCUSSION: Occurrence of laryngopharyngeal dysesthesia due to oxaliplatin does not warrant drug withdrawal, dose titration can be helpful, thereby preventing the drug withdrawal for the patient management.
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Antineoplásicos , Neoplasias Colorrectales , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Desoxicitidina , Disartria , Femenino , Fluorouracilo , Humanos , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversos , Oxaliplatino/efectos adversos , Dolor/tratamiento farmacológico , Parestesia/inducido químicamente , Parestesia/tratamiento farmacológico , HablaRESUMEN
INTRODUCTION: Vortioxetine, a multimodal serotonergic drug, is widely used as treatment for major depressive disorder. Although on the market since late 2013, the data of the relative safety of vortioxetine, especially compared to selective serotonin reuptake inhibitors, are still scarce. OBJECTIVE: The aim of this study was to explore the adverse event reporting pattern of vortioxetine through a cluster analysis. Furthermore, to compare the adverse event reporting pattern for vortioxetine with that of the selective serotonin reuptake inhibitors. METHODS: Individual case safety reports for vortioxetine in VigiBase up to 1 November, 2019 were subjected to consensus clustering, to identify and describe natural groupings of reports based on their reported adverse events. A vigiPoint exploratory analysis compared vortioxetine to the selective serotonin reuptake inhibitors in terms of relative frequencies for a wide range of covariates, including patient sex and age, reported drugs and adverse events, and reporting country. Important differences were identified using odds ratios with adaptive statistical shrinkage. RESULTS: Thirty-six clusters containing at least five reports were identified and analysed. The two largest clusters included 48% of the vortioxetine reports and appeared to represent gastrointestinal adverse events and hypersensitivity adverse events. Other distinct clusters were related to, respectively, fatigue, aggression/suicidality, convulsion, medication errors, arthralgia/myalgia, increased weight, paraesthesia and anticholinergic effects. Some of these clusters are not labelled for vortioxetine, such as arthralgia/myalgia and paraesthesia, but are known adverse events for selective serotonin reuptake inhibitors. A vigiPoint analysis revealed a higher proportion of reports from consumers and non-health professionals for vortioxetine as well as higher relative reporting rates of gastrointestinal symptoms, pruritus and mood-related symptoms, consistent with the cluster analysis. CONCLUSIONS: A pattern of co-reported adverse events that is consistent with labelled adverse events for vortioxetine and the safety profile for selective serotonin reuptake inhibitors in general was revealed. Clusters of unlabelled adverse events were identified that reflect clinical entities that might represent signals of previously unknown adverse events. More extensive analyses of spontaneous reports may help to further understand the reporting pattern of adverse events.
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Trastorno Depresivo Mayor , Inhibidores Selectivos de la Recaptación de Serotonina , Artralgia/inducido químicamente , Artralgia/tratamiento farmacológico , Análisis por Conglomerados , Trastorno Depresivo Mayor/inducido químicamente , Trastorno Depresivo Mayor/tratamiento farmacológico , Humanos , Mercadotecnía , Mialgia/inducido químicamente , Parestesia/inducido químicamente , Parestesia/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Vortioxetina/efectos adversosRESUMEN
POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare plasma cell dyscrasia without standard front-line treatment. Merely, few studies have reported the responses and outcomes of bortezomib plus dexamethasone (BDex) in POEMS syndrome. In this study, a total of 69 patients (40 males) treated with front-line BDex were included. The median age at diagnosis was 50 years (range, 30-78 years). After a median of 9 cycles BDex (range 1-9), fifty-two (88.1%), thirty-two (46.4%), and forty-seven (71.2%) patients achieved the best neurologic response, hematological complete response, and serum vascular endothelial growth factor (VEGF) response, respectively. The extravascular overload, pulmonary hypertension, and renal impairment also substantially improved. No treatment-related death occurred. Two patients developed grade-1 bortezomib-induced peripheral neuropathy and were reversible after drug withdrawal. After a median follow-up of 22.5 months, the estimated 2-year overall survival and time to next treatment were 95.7% and 65.6%, respectively. In conclusion, the combination of bortezomib and dexamethasone is effective, with a high response rate and safety profile for patients with newly diagnosed POEMS syndrome.
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Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Síndrome POEMS/tratamiento farmacológico , Adulto , Anciano , Biomarcadores , Bortezomib/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Dexametasona/efectos adversos , Diarrea/inducido químicamente , Evaluación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Síndrome POEMS/sangre , Paraproteínas/análisis , Parestesia/inducido químicamente , Estudios Retrospectivos , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
A 54-year-old woman presented with a 1-month history of pain and numbness in both feet. She had taken metronidazole for over 4 years previously to treat vaginitis. On nerve conduction studies (NCS), neither the sural nor right superficial peroneal nerve (SPN) was evoked, nor did the left SPN have small amplitude, suggesting axonal peripheral polyneuropathy with sensory fiber involvement. When she restarted metronidazole, she immediately complained of recurrent paresthesia of the feet. We performed three electromyography (EMG) studies and followed the patient for 6 months.
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Metronidazol , Parestesia , Electromiografía , Femenino , Humanos , Metronidazol/efectos adversos , Persona de Mediana Edad , Conducción Nerviosa , Parestesia/inducido químicamente , Nervio PeroneoAsunto(s)
Inhibidores de Puntos de Control Inmunológico/efectos adversos , Melanoma/tratamiento farmacológico , Enfermedades Musculares/inducido químicamente , Miositis/inducido químicamente , Miotonía Congénita/complicaciones , Distrofia Miotónica/complicaciones , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Cardiomiopatía Dilatada , Canales de Cloruro/genética , Conectina/genética , Trastornos de Deglución/inducido químicamente , Trastornos de Deglución/complicaciones , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/fisiopatología , Electrodiagnóstico , Electromiografía , Humanos , Ipilimumab/efectos adversos , Imagen por Resonancia Magnética , Masculino , Melanoma/secundario , Enfermedades Musculares/complicaciones , Enfermedades Musculares/genética , Enfermedades Musculares/fisiopatología , Miositis/complicaciones , Miositis/diagnóstico , Miositis/fisiopatología , Miotonía Congénita/diagnóstico , Miotonía Congénita/genética , Miotonía Congénita/fisiopatología , Distrofia Miotónica/diagnóstico , Distrofia Miotónica/fisiopatología , Conducción Nerviosa , Nivolumab/efectos adversos , Parestesia/inducido químicamente , Parestesia/complicaciones , Parestesia/fisiopatología , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Proteínas de Unión al ARN/genética , Neoplasias Cutáneas/patología , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Neoplasias de la Columna Vertebral/secundarioRESUMEN
OBJECTIVE: Osteoarthritis (OA) is the most common joint disease and leading cause of pain and disability in the elderly population. Most guidelines recommend the use of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids for the non-operative treatment of OA. Monoclonal nerve growth factor (NGF) antibodies are new drugs with the potential to provide pain relief and functional improvement in OA. We compared the efficacy (pain reduction and functional improvement), and safety of monoclonal NGF antibodies with NSAIDs and opioids in the treatment of OA with a Bayesian network meta-analysis. RESULTS: 38 articles, comprising 41 trials and 20489 patients with OA were included. Overall from the network meta-analysis, anti-NGFs were the most effective drugs for pain relief (Standardized Mean Difference or SMD compared with placebo 4.25, 95% CI 2.87 to 5.63, Surface Under the Cumulative RAnking curve or SUCRA=93.7%) and for functional improvement (SMD 4.90, 95% CI 3.46 to 6.33, SUCRA=98.3%). Although anti-NGFs were associated with higher risk of peripheral sensation abnormality (paresthesia and pruritus), they were not associated with higher risk of other AEs (headaches and nausea) or with higher withdrawal rates related to AEs. CONCLUSIONS: Monoclonal NGF antibodies provide significantly greater pain relief and functional improvement in OA compared to NSAIDs and opioids. Monoclonal NGF antibodies are not associated with severe AEs. More studies are needed to confirm these findings. METHODS: PubMed, CNKI, Web of Science, Scopus, Embase and Cochrane Library databases were searched for relevant studies (OA treated with anti-NGFs, opioids, selective COX-2 inhibitors or NSAIDs) published between January 1999 to January 2020. Bayesian network and conventional meta-analyses were conducted. Pain relief, functional improvement and AEs were assessed.
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Analgésicos Opioides/uso terapéutico , Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Factor de Crecimiento Nervioso/antagonistas & inhibidores , Osteoartritis/tratamiento farmacológico , Dimensión del Dolor , Rendimiento Físico Funcional , Anticuerpos Monoclonales Humanizados/uso terapéutico , Teorema de Bayes , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Cefalea/inducido químicamente , Humanos , Terapia Molecular Dirigida , Náusea/inducido químicamente , Factor de Crecimiento Nervioso/inmunología , Metaanálisis en Red , Osteoartritis/fisiopatología , Parestesia/inducido químicamente , Prurito/inducido químicamenteRESUMEN
Palmar plantar erythrodysesthesia (PPE) is a commonly reported skin toxicity of chemotherapeutic agents that significantly affects patients' quality of life. PPE is described as inflammation, swelling, and even cracks and ulcers in the skin of palms and soles of the feet. Conventional treatment includes topical creams, analgesics, or corticosteroids. However, serious cases are not responding to these medications. PPE has been reported to cause drug cessation or dose reduction if not properly treated. Sildenafil citrate (SC) has a well-documented activity in wound healing through improving blood supply to the affected area. However, SC has poor physicochemical properties limiting its transdermal permeation and deposition. This research endeavored to elaborate novel vesicular system with natural components, phospholipids and oleic acid, loaded with sildenafil citrate for topical management of PPE. Sildenafil-loaded oleosomes were prepared using modified ethanol injection method. Optimized oleosomes had nanometric particle size (157.6 nm), negative zeta potential (- 85.2 mv), and high entrapment efficiency (95.56%). Ex vivo studies on human skin revealed that oleosomes displayed 2.3-folds higher permeation and 4.5-folds more deposition through the human skin compared to drug suspension. Results endorsed SC oleosomes as suitable topical treatment of PPE providing ameliorated sildenafil permeability in addition to acting as a reservoir for gradual release of the drug. Graphical abstract.
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Antineoplásicos/efectos adversos , Gotas Lipídicas , Parestesia/tratamiento farmacológico , Citrato de Sildenafil/química , Enfermedades de la Piel/tratamiento farmacológico , Administración Tópica , Humanos , Parestesia/inducido químicamente , Parestesia/complicaciones , Tamaño de la Partícula , Calidad de Vida , Citrato de Sildenafil/administración & dosificación , Citrato de Sildenafil/uso terapéutico , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/complicacionesRESUMEN
Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely hyposalivation, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, reactive keratosis, dysesthesia, osteonecrosis, infection, angioedema, and malignancy.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/complicaciones , Erupciones Liquenoides/inducido químicamente , Enfermedades de la Boca/inducido químicamente , Boca/patología , Animales , Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Humanos , Hiperpigmentación/inducido químicamente , Hiperplasia/inducido químicamente , Leucoplasia/inducido químicamente , Neoplasias de la Boca/inducido químicamente , Úlceras Bucales/inducido químicamente , Parestesia/inducido químicamente , Enfermedades Cutáneas Vesiculoampollosas/inducido químicamente , Xerostomía/inducido químicamenteRESUMEN
OBJECTIVE: Tanezumab, a nerve growth factor inhibitor, was investigated for osteoarthritis (OA) of the hip or knee in a study with 24-week treatment and 24-week safety follow-up. METHODS: This double-blind, randomised, phase III study enrolled adults in Europe and Japan with moderate-to-severe OA who had not responded to or could not tolerate standard-of-care analgesics. Patients were randomised to tanezumab 2.5 mg or 5 mg subcutaneously or matching placebo every 8 weeks (three doses). Co-primary end points were change from baseline to week 24 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function, and Patient's Global Assessment of OA (PGA-OA). Joint safety and neurological assessments continued throughout the 48-week study. RESULTS: From March 2016 to December 2017, 849 patients were randomised and evaluated (placebo n=282, tanezumab 2.5 mg n=283, tanezumab 5 mg n=284). At week 24, there was a statistically significant improvement from baseline for tanezumab 5 mg compared with placebo for WOMAC Pain (least squares mean difference±SE -0.62±0.18, p=0.0006), WOMAC Physical Function (-0.71±0.17, p<0.0001) and PGA-OA (-0.19±0.07, p=0.0051). For tanezumab 2.5 mg, there was a statistically significant improvement in WOMAC Pain and Physical Function, but not PGA-OA. Rapidly progressive osteoarthritis (RPOA) was observed in 1.4% (4/283) and 2.8% (8/284) of patients in the tanezumab 2.5 mg and tanezumab 5 mg groups, respectively and none receiving placebo. Total joint replacements (TJRs) were similarly distributed across all three treatment groups (6.7%-7.8%). Tanezumab-treated patients experienced more paraesthesia (5 mg) and hypoaesthesia (both doses) than placebo. CONCLUSION: Tanezumab 5 mg statistically significantly improved pain, physical function and PGA-OA, but tanezumab 2.5 mg only achieved two co-primary end points. RPOA occurred more frequently with tanezumab 5 mg than tanezumab 2.5 mg. TJRs were similarly distributed across all three groups. TRIAL REGISTRATION NUMBER: NCT02709486.
Asunto(s)
Analgésicos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Dolor Musculoesquelético/tratamiento farmacológico , Osteoartritis de la Cadera/tratamiento farmacológico , Osteoartritis de la Rodilla/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Hipoestesia/inducido químicamente , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Dolor Musculoesquelético/etiología , Osteoartritis de la Cadera/complicaciones , Osteoartritis de la Cadera/cirugía , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/cirugía , Dimensión del Dolor , Parestesia/inducido químicamente , Rendimiento Físico FuncionalRESUMEN
PURPOSE: This study aims to (1) examine the prevalence of painful versus non-painful chemotherapy-induced peripheral neuropathy (CIPN) among long-term colorectal cancer (CRC) survivors, (2) identify sociodemographic, clinical, and psychological factors associated with painful and non-painful CIPN, and (3) examine the associations of painful CIPN with health-related quality of life (HRQoL) in comparison with non-painful CIPN, i.e., numbness/tingling. METHODS: All CRC survivors diagnosed between 2000 and 2009 as registered by the population-based Netherlands Cancer Registry (Eindhoven region) were eligible for participation. Chemotherapy-treated survivors (n = 477) completed questions on CIPN (EORTC QLQ-CIPN20) and HRQoL (EORTC QLQ-C30). RESULTS: Painful CIPN was reported by 9% (n = 45) of survivors and non-painful CIPN was reported by 22% (n = 103). Time since diagnosis was related to painful CIPN, and time since diagnosis, a higher disease stage, osteoarthritis, and more anxiety symptoms were related to non-painful CIPN. Finally, survivors with painful CIPN reported a worse global quality of life and worse physical, role, cognitive, and social functioning compared to survivors with non-painful CIPN and those without any sensory CIPN. No differences were found between survivors with non-painful CIPN and those without sensory CIPN. CONCLUSIONS: It seems that painful CIPN must be distinguished from non-painful CIPN, as only painful CIPN was related to a worse HRQoL. Future research is needed to examine whether painful CIPN must be distinguished from non-painful CIPN regarding predictors, mechanisms, and treatment.