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1.
World J Urol ; 41(11): 3065-3074, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37787942

RESUMO

PURPOSE: Despite advances in technology, such as advent of laser enucleation and minimally invasive surgical therapies, transurethral resection of the prostate (TURP) remains the most widely performed surgical technique for benign prostatic hyperplasia (BPH). We evaluated resection volume (RV)-derived parameters and analyzed the effect of RV on post-TURP outcomes. METHODS: This observational study used data from patients who underwent TURP at two institutions between January 2011 and December 2021 Data from patients with previous BPH surgical treatment, incomplete data, and underlying disease affecting voiding function were excluded. The collected data included age, prostate-specific antigen, transrectal ultrasound (TRUS)- and uroflowmetry-derived parameters, RV, perioperative laboratory values, perioperative International Prostatic Symptom Score (IPSS), follow-up period, retreatment requirements and interval between the first TURP and retreatment. RESULTS: In 268 patients without prior BPH medication, there were no differences in prostate volume (PV), transitional zone volume (TZV), or RV according to IPSS. A total of 60 patients started retreatment, including medical or surgical treatment, within the follow-up period. There was a significant difference in RV/PV between the groups without and with retreatment respectively (0.56 and 0.37; p = 0.008). However, preoperative TRUS- and uroflowmetry-derived parameters did not differ between the two groups. Multiple linear regression analysis showed that RV (p = 0.003) and RV/TZV (p = 0.006) were significantly associated with differences in perioperative IPSS. In the multivariate logistic regression analysis, only RV/PV was correlated with retreatment (p = 0.010). CONCLUSION: Maximal TURP leads to improved postoperative outcomes and reduced retreatment rate, it may gradually become a requirement rather than an option.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/cirurgia , Ressecção Transuretral da Próstata/métodos , Hiperplasia Prostática/complicações , Micção , Resultado do Tratamento , Retratamento
2.
Scand J Urol ; 56(4): 336-341, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35942595

RESUMO

INTRODUCTION: CoreTherm (ProstaLund AB, Lund, Sweden) is an outpatient treatment option in men with lower urinary tract symptoms and catheter-dependent men with chronic urinary retention caused by benign prostatic obstruction (BPO). CoreTherm is high-energy transurethral microwave thermotherapy with feedback technique. Modern treatment with CoreTherm includes transurethral intraprostatic injections of mepivacaine and adrenaline via the Schelin Catheter (ProstaLund AB, Lund, Sweden) and is often referred to as the CoreTherm Concept. OBJECTIVES: The aim of this study was to evaluate the short- and long-term retreatment risk in men with large prostates and BPO or chronic urinary retention, all primarily treated with CoreTherm. MATERIAL AND METHODS: All men from the same geographical area with prostate volumes ≥ 80 ml treated 1999-2015 with CoreTherm and having BPO or were catheter-dependent due to chronic urinary retention, were included. End of study period was defined as December 31, 2019. RESULTS: We identified and evaluated 570 men treated with CoreTherm, where 12% (71 patients) were surgically retreated during the follow-up. Mean follow-up was 11 years, and maximum follow-up was 20 years. The long-term retreatment rate in our study was 23%. A majority of these could be retreated with CoreTherm or TURP, with only 3% requiring open surgery. CONCLUSION: We conclude that CoreTherm is a suitable outpatient treatment option in patients with profoundly enlarged prostates, regardless of age, prostate size, and reason for treatment.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Retenção Urinária , Epinefrina , Humanos , Masculino , Mepivacaína , Próstata , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/terapia , Retratamento , Ressecção Transuretral da Próstata/métodos , Resultado do Tratamento , Retenção Urinária/cirurgia , Retenção Urinária/terapia
4.
Gastroenterology ; 162(3): 920-934, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35210014

RESUMO

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC), the most common primary liver cancer, remains a deadly cancer, with an incidence that has tripled in the United States since 1980. In recent years, new systemic therapies for HCC have been approved and a critical assessment of the existing data is necessary to balance benefits and harms and inform the development of evidence-based guidelines. METHODS: The American Gastroenterological Association formed a multidisciplinary group consisting of a Technical Review Panel and a Guideline Panel. The Technical Review Panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and conducted an evidence review of systemic therapies in patients with advanced-stage HCC. The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence. The Guideline Panel reviewed the evidence and used the Evidence-to-Decision Framework to develop recommendations. RESULTS: The Panel reviewed the evidence, summarized in the Technical Review, for the following medications approved by the US Food and Drug Administration for HCC: first-line therapies: bevacizumab+atezolizumab, sorafenib, and lenvatinib; second-line therapies: cabozantinib, pembrolizumab, ramucirumab, and regorafenib; and other agents: bevacizumab, nivolumab, and nivolumab+ipilimumab. CONCLUSIONS: The Panel agreed on 11 recommendations focused on systemic therapy for HCC in patients who are not eligible for locoregional therapy or resection, those with metastatic disease and preserved liver function, those with poor liver function, and those on systemic therapy as adjuvant therapy.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Anilidas/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab/administração & dosagem , Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/cirurgia , Quimioembolização Terapêutica , Quimioterapia Adjuvante , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Quinolinas/uso terapêutico , Retratamento , Sorafenibe/uso terapêutico , Ramucirumab
5.
Br J Haematol ; 196(3): 473-487, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34448202

RESUMO

The management of older individuals (≥60 years) with primary central nervous system lymphoma remains a clinical challenge. Identification of optimal therapy and delivering adequate dose intensity are two of the major issues in treating elderly patients. Premorbid performance status and comorbidities influence individualised treatment approaches and geriatric assessment tools are increasingly utilised. Optimal induction treatment remains high-dose methotrexate-based immunochemotherapy, delivery is feasible in the majority of patients and the goal of treatment remains achieving complete remission. Consolidation strategies are also relevant in the elderly, aiming to maximise duration of response and quality of life (QoL). Potential options include high-dose therapy with haematopoietic stem cell consolidation, non-myeloablative chemotherapy and whole-brain radiotherapy. Efficacy of novel agents, such as Bruton tyrosine kinase inhibitors and lenalidomide, have been reported; these represent an alternative for elderly patients unfit for chemotherapy. Prognosis remains poor, improvement of outcomes in this age group is urgently needed.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Linfoma não Hodgkin/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/etiologia , Tomada de Decisão Clínica , Terapia Combinada/métodos , Gerenciamento Clínico , Avaliação Geriátrica , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/etiologia , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Qualidade de Vida , Retratamento , Resultado do Tratamento
6.
Clin Oral Investig ; 26(1): 1045-1052, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34392407

RESUMO

OBJECTIVE: To evaluate the percentage volume of voids and gaps in oval-shaped canals obturated using two different methods with a tricalcium silicate-based sealer after short- or long-term storage. The long-term effect of storage on the efficiency of removing filling material was also investigated. MATERIALS AND METHODS: Forty premolar teeth with oval-shaped canals were instrumented to Reciproc R25 and obturated using single cone obturation (SCO) or warm vertical compaction (WVC) techniques with gutta-percha and HiFlow sealer. The specimens were stored at 100% humidity and 37°C for 2 weeks or 6 months and scanned using micro-computed tomography. Initial retreatment was performed up to a Reciproc R40, and the operating time was recorded. The residual material in the canal received a supplementary procedure using XP-endo Finisher R (XPFR) files. After each retreatment procedure, the specimens were rescanned. RESULTS: The percentage volume of voids and gaps in the SCO group was higher than that of the WVC group at both 2 weeks and 6 months (P < 0.05). The percentage volume of the filling material removed after initial retreatment and XPFR cleaning was significantly higher in the 6-month group than in the 2-week groups (P < 0.05). The proportion of the residual material decreased significantly when XPFR files were used, compared to the initial retreatment group (P < 0.05) in both storage times. CONCLUSION: The efficiency of retreatment in the oval-shaped canal was closely related to the storage time rather than the filling technique using a tricalcium silicate sealer. The XPFR instrument proved effective in the removal of the remaining materials from the oval-shaped canal. CLINICAL RELEVANCE: Obturation of the oval-shaped canal with TSBS using the SCO technique in the coronal area needs to be optimized. The retreatment was less efficacious in freshly filled canals than aged filled canals.


Assuntos
Materiais Restauradores do Canal Radicular , Obturação do Canal Radicular , Compostos de Cálcio , Cavidade Pulpar/diagnóstico por imagem , Guta-Percha , Porosidade , Retratamento , Preparo de Canal Radicular , Silicatos , Microtomografia por Raio-X
7.
Araçatuba; s.n; 2022. 89 p. tab, ilus.
Tese em Inglês | LILACS, BBO | ID: biblio-1434748

RESUMO

Este trabalho objetivou realizar duas revisões sistemáticas com as seguintes propostas: 1) Avaliar se a fototerapia com laser resultaria em menor dor pós-operatória (PP) em pacientes submetidos a reintervenção endodôntica; e 2) Avaliar se o uso da terapia fotodinâmica antimicrobiana (aPDT) seria eficaz na desinfecção de canais radiculares em casos de reintervenção endodôntica. As Revisões Sistemáticas foram registradas no PROSPERO (CRD42021243500 e CRD42021260013, respectivamente) e seguiram as diretrizes dos Itens de Relatório Preferenciais para Revisões Sistemáticas e Meta-análise (PRISMA). As buscas foram realizadas nas bases de dados eletrônicas PubMeb, Scopus, Web of Science, Embase, Web of Science, Clinical Trials e Cochrane Library e nos bancos de dados da literatura cinza. A qualidade metodológica e o risco de viés foram avaliados pela ferramenta Cochrane Risk of Bias para ensaios clínicos randomizados (RCT) e pelo qualificador NewcastleOttawa (NOS) para estudos não RCT (prospectivos). A análise da qualidade de evidência foi realizada com base na abordagem GRADE. A meta-análise foi realizada com o R software Meta package, utilizando um intervalo de confiança (IC) de 95%. Quanto aos resultados do Artigo 1: Cinco artigos foram incluídos para análise. Os estudos foram classificados como "baixo" risco de viés. Dos cinco estudos clínicos, quatro estudos mostraram uma diminuição significativa da PP após a reintervenção endodôntica nos grupos de fototerapia a laser quando comparados ao grupo controle, principalmente nos primeiros dias após a intervenção. A certeza de evidência foi classificada como baixa. Devido à alta heterogeneidade clínica entre os estudos, não foi possível realizar qualquer meta-análise. Apesar das limitações desta revisão sistemática, a fototerapia se mostrou uma alternativa promissora na redução e controle da PP na reintervenção endodôntica não cirúrgica. Nos resultados do Artigo 2, dez estudos atenderam aos critérios de elegibilidade e foram incluídos, sendo 8 utilizados na síntese quantitativa. A meta-análise mostrou que todos os dados dos estudos apresentaram diferença significativa antes e depois da terapia fotodinâmica antimicrobiana na redução da carga microbiana em infecções endondônticas secundárias (OR 0,15 [0,07; 0,32], p < 0,0001). No geral, os estudos apresentaram baixo risco de viés e a análise das evidências foi classificada como moderada. Sugere-se que a terapia fotodinâmica seja uma ferramenta benéfica e promissora, mostrando eficácia na redução da carga microbiana nos casos de reintervenção endodôntica. Em suma, a abordagem da utilização da fototerapia se demonstrou eficaz na diminuição da dor pós-operatória e na desinfecção dos canais radiculares, podendo ser uma terapia indicada nos casos de reintervenção endodôntica(AU)


This study aimed to carry out two systematic reviews with the following proposals: 1) Evaluate whether laser phototherapy would result in less postoperative pain (PP) in patients undergoing endodontic reintervention; and 2) Evaluate whether the use of antimicrobial photodynamic therapy (aPDT) would be effective in disinfection of root canals in cases of endodontic reintervention. Systematic Reviews were registered in PROSPERO (CRD42021243500 and CRD42021260013, respectively) and followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Metaanalysis (PRISMA). Searches were performed in the electronic databases PubMeb, Scopus, Web of Science, Embase, Web of Science, Clinical Trials and Cochrane Library and in the gray literature databases. Methodological quality and risk of bias were assessed by the Cochrane Risk of Bias tool for randomized clinical trials (RCT) and by the Newcastle-Ottawa (NOS) qualifier for non-RCT (prospective) studies. The analysis of the quality of evidence was performed based on the GRADE approach. The meta-analysis was performed using the R Meta package software, using a 95% confidence interval (CI). As for the results of Article 1: Five articles were included for analysis. Studies were classified as "low" risk of bias. Of the five clinical studies, four studies showed a significant decrease in PP after endodontic reintervention in the laser phototherapy groups when compared to the control group, mainly in the first days after the intervention. The certainty of evidence was rated low. Due to the high clinical heterogeneity between studies, it was not possible to perform any meta-analysis. Despite the limitations of this systematic review, phototherapy proved to be a promising alternative for the reduction and control of PP in conventional endodontic reintervention. In the results of Article 2, ten studies met the eligibility criteria and were included, being 8 used in the quantitative synthesis. The meta-analysis showed that all data from the studies showed a significant difference before and after antimicrobial photodynamic therapy in reducing the microbial load in secondary endodontic infections (OR 0.15 [0.07; 0.32], p < 0.0001). Overall, the studies presented a low risk of bias and the analysis of evidence was rated as moderate. It is suggested that photodynamic therapy is a beneficial and promising tool, showing efficacy in reducing the microbial load in cases of endodontic reintervention. In summary, the approach to the use of phototherapy has been shown to be effective in reducing postoperative pain and disinfection of root canals, and may be an indicated therapy in cases of endodontic reintervention(AU)


Assuntos
Fototerapia , Fotoquimioterapia , Tratamento do Canal Radicular , Dente não Vital , Retratamento , Dor Pós-Operatória , Obturação do Canal Radicular , Desinfecção , Cavidade Pulpar , Lasers , Antibacterianos
8.
Int Endod J ; 54(11): 2006-2015, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34383325

RESUMO

AIM: To compare the effect of low-level laser therapy (LLLT) on postoperative pain after single-visit root canal retreatment on mandibular molars. METHODOLOGY: This randomized controlled clinical trial included 36 patients referred to the Department of Endodontics, Islamic Azad University, Tehran, Iran. Healthy patients who required root canal retreatment on symptomatic first or second mandibular molars, with a PAI index score of 2 or 3, preoperative tooth and percussion pain of <56 mm on a 170-mm visual analogue scale (VAS) were included. After local anaesthesia using inferior alveolar nerve block followed by rubber dam isolation and access cavity preparation, the D RaCe retreatment system was used to remove the existing root filling material, and after canal negotiation and gaining patency, working length was determined with an apex locator. Further canal enlargement was carried out with size 35, 0.04 taper, and size 40, 0.04 taper RaCe rotary instruments and then canals were filled using laterally compacted gutta-percha points and AH Plus sealer. The patients were randomly assigned to treatment groups: In the LLLT group, a 980-nm diode laser set at 6.89 W/cm2 energy density, 0.5 W power, and a tip diameter of 10 mm were activated from the buccal side on the mesial and distal root apices for 15 s. In the sham group, the laser handpiece was placed inside the patient's mouth at the same location, but the laser was not activated. Then patients were instructed to record their postoperative pain levels at 4, 8, 12 and 24 h and 2, 3 and 7 days after treatment on separate VAS scales. For data analysis, the independent sample t and the Mann-Whitney U tests were used. Nominal variables were analysed by using the chi-square test. RESULTS: In the LLLT group, the most intense pain was reported 24 and 48 h post-treatment [mean (SD) = 0.22 (0.54) for both], whereas in the sham group, the most intense pain level was observed 4 h post-treatment [mean (SD) = 0.78 (0.80)]. At the 4-h interval, pain intensity was significantly lower in the LLLT group (p = .016). CONCLUSIONS: Low-level laser therapy reduced postoperative pain after single-visit root canal retreatment of mandibular molars only four hours following the procedure.


Assuntos
Terapia com Luz de Baixa Intensidade , Cavidade Pulpar , Humanos , Irã (Geográfico) , Dente Molar/cirurgia , Dor Pós-Operatória , Retratamento , Preparo de Canal Radicular
9.
Urol Int ; 105(9-10): 869-874, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34289488

RESUMO

INTRODUCTION: The aim of the study is to compare length of hospital stay, transfusion rates, and re-intervention rates during hospitalization for transurethral resection of the prostate (TUR-P), open prostatectomy (OP), and laser therapy (LT) for surgical treatment of benign prostatic obstruction (BPO). METHODS: URO-Cert is an organization, in which clinical data of prostatic diseases from 2 university, 19 public, and 3 private hospitals and 270 office-based urologists are collected in order to document treatment quality. Data on diagnostics, therapy, and course of disease are recorded web based. The analysis includes datasets from 2005 to 2017. RESULTS: Of 10,420 patients, 8,389 were treated with TUR-P, 1,334 with OP, and 697 with LT. Median length of hospital stay was 6 days (IQR: 4-7) for TUR-P, 9 days (IQR: 7-11) for OP, and 5 days (IQR: 4-6) for LT (p < 0.001). Risk for a hospital stay ≥7 days was higher for OP versus TUR-P (OR: 7.25; 95% CI = 6.27-8.36; p < 0.001) and LT (OR: 17.89; 95% CI = 14.12-22.65; p < 0.001) and higher for TUR-P versus LT (OR: 2.47; 95% CI = 2.03-3.01; p < 0.001). OP had a significantly higher risk for transfusions than TUR-P (OR: 2.44; 95% CI = 1.74-3.41; p < 0.001) and LT (OR: 3.32; 95% CI = 1.56-7.01; p < 0.001). Transfusion rates were not significantly different between TUR-P and LT (OR: 1.36; 95% CI = 0.66-2.79; p = 0.51). Risk of re-intervention was not different between all 3 approaches. CONCLUSION: OP was associated with higher transfusion rates and longer hospital stay than TUR-P and LT. Risk of transfusion was not different between TUR-P and LT, but TUR-P was inferior to LT concerning length of hospital stay. Re-intervention rates during hospitalization did not differ between the groups.


Assuntos
Terapia a Laser , Sintomas do Trato Urinário Inferior/cirurgia , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata , Idoso , Transfusão de Sangue , Bases de Dados Factuais , Alemanha , Humanos , Terapia a Laser/efeitos adversos , Tempo de Internação , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Complicações Pós-Operatórias/terapia , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/fisiopatologia , Recuperação de Função Fisiológica , Retratamento , Fatores de Tempo , Ressecção Transuretral da Próstata/efeitos adversos , Resultado do Tratamento , Urodinâmica
10.
Cochrane Database Syst Rev ; 6: CD004135, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34180047

RESUMO

BACKGROUND: Transurethral resection of the prostate (TURP) has been the gold-standard treatment for alleviating urinary symptoms and improving urinary flow in men with symptomatic benign prostatic hyperplasia (BPH). However, the morbidity of TURP approaches 20%, and less invasive techniques have been developed for treating BPH. Transurethral microwave thermotherapy (TUMT) is an alternative, minimally-invasive treatment that delivers microwave energy to produce coagulation necrosis in prostatic tissue. This is an update of a review last published in 2012. OBJECTIVES: To assess the effects of transurethral microwave thermotherapy for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, Web of Science, and LILACS), trials registries, other sources of grey literature, and conference proceedings published up to 31 May 2021, with no restrictions by language or publication status. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) and cluster-RCTs of participants with BPH who underwent TUMT. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion at each stage and undertook data extraction and risk of bias and GRADE assessments of the certainty of the evidence (CoE). We considered review outcomes measured up to 12 months after randomization as short-term and beyond 12 months as long-term. Our main outcomes included: urologic symptoms scores, quality of life, major adverse events, retreatment, and ejaculatory and erectile function. MAIN RESULTS: In this update, we identified no new RCTs, but we included data from studies excluded in the previous version of this review. We included 16 trials with 1919 participants, with a median age of 69 and moderate lower urinary tract symptoms. The certainty of the evidence for most comparisons was moderate-to-low, due to an overall high risk of bias across studies and imprecision (few participants and events). TUMT versus TURP Based on data from four studies with 306 participants, when compared to TURP, TUMT probably results in little to no difference in urologic symptom scores measured by the International Prostatic Symptom Score (IPSS) on a scale from 0 to 35, with higher scores indicating worse symptoms at short-term follow-up (mean difference (MD) 1.00, 95% confidence interval (CI) -0.03 to 2.03; moderate certainty). There is likely to be little to no difference in the quality of life (MD -0.10, 95% CI -0.67 to 0.47; 1 study, 136 participants, moderate certainty). TUMT likely results in fewer major adverse events (RR 0.20, 95% CI 0.09 to 0.43; 6 studies, 525 participants, moderate certainty); based on 168 cases per 1000 men in the TURP group, this corresponds to 135 fewer (153 to 96 fewer) per 1000 men in the TUMT group. TUMT, however, probably results in a large increase in the need for retreatment (risk ratio (RR) 7.07, 95% CI 1.94 to 25.82; 5 studies, 337 participants, moderate certainty) (usually by repeated TUMT or TURP); based on zero cases per 1000 men in the TURP group, this corresponds to 90 more (40 to 150 more) per 1000 men in the TUMT group. There may be little to no difference in erectile function between these interventions (RR 0.63, 95% CI 0.24 to 1.63; 5 studies, 337 participants; low certainty). However, TUMT may result in fewer cases of ejaculatory dysfunction compared to TURP (RR 0.36, 95% CI 0.24 to 0.53; 4 studies, 241 participants; low certainty). TUMT versus sham Based on data from four studies with 483 participants we found that, when compared to sham, TUMT probably reduces urologic symptom scores using the IPSS at short-term follow-up (MD -5.40, 95% CI -6.97 to -3.84; moderate certainty). TUMT may cause little to no difference in the quality of life (MD -0.95, 95% CI -1.14 to -0.77; 2 studies, 347 participants; low certainty) as measured by the IPSS quality-of-life question on a scale from 0 to 6, with higher scores indicating a worse quality of life. We are very uncertain about the effects on major adverse events, since most studies reported no events or isolated lesions of the urinary tract. TUMT may also reduce the need for retreatment compared to sham (RR 0.27, 95% CI 0.08 to 0.88; 2 studies, 82 participants, low certainty); based on 194 retreatments per 1000 men in the sham group, this corresponds to 141 fewer (178 to 23 fewer) per 1000 men in the TUMT group. We are very uncertain of the effects on erectile and ejaculatory function (very low certainty), since we found isolated reports of impotence and ejaculatory disorders (anejaculation and hematospermia). There were no data available for the comparisons of TUMT versus convective radiofrequency water vapor therapy, prostatic urethral lift, prostatic arterial embolization or temporary implantable nitinol device. AUTHORS' CONCLUSIONS: TUMT provides a similar reduction in urinary symptoms compared to the standard treatment (TURP), with fewer major adverse events and fewer cases of ejaculatory dysfunction at short-term follow-up. However, TUMT probably results in a large increase in retreatment rates. Study limitations and imprecision reduced the confidence we can place in these results. Furthermore, most studies were performed over 20 years ago. Given the emergence of newer minimally-invasive treatments, high-quality head-to-head trials with longer follow-up are needed to clarify their relative effectiveness. Patients' values and preferences, their comorbidities and the effects of other available minimally-invasive procedures, among other factors, can guide clinicians when choosing the optimal treatment for this condition.


Assuntos
Hipertermia Induzida/métodos , Sintomas do Trato Urinário Inferior/terapia , Micro-Ondas/uso terapêutico , Hiperplasia Prostática/terapia , Terapia por Radiofrequência/métodos , Antagonistas Adrenérgicos alfa/uso terapêutico , Idoso , Ejaculação , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Micro-Ondas/efeitos adversos , Ereção Peniana , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Retratamento , Ressecção Transuretral da Próstata/efeitos adversos
11.
Br J Radiol ; 94(1126): 20210477, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34161167

RESUMO

This review summarises the current knowledge about recurrent radiological imaging and associated cumulative doses to patients. The recent conservative estimates are for around 0.9 million patients globally who cumulate radiation doses above 100 mSv, where evidence exists for cancer risk elevation. Around one in five is estimated to be under the age of 50. Recurrent imaging is used for managing various health conditions and chronic diseases such as malignancies, trauma, end-stage kidney disease, cardiovascular diseases, Crohn's disease, urolithiasis, cystic pulmonary disease. More studies are needed from different parts of the world to understand the magnitude and appropriateness. The analysis identified areas of future work to improve radiation protection of individuals who are submitted to frequent imaging. These include access to dose saving imaging technologies; improved imaging strategies and appropriateness process; specific optimisation tailored to the clinical condition and patient habitus; wider utilisation of the automatic exposure monitoring systems with an integrated option for individual exposure tracking in standardised patient-specific risk metrics; improved training and communication. The integration of the clinical and exposure history data will support improved knowledge about radiation risks from low doses and individual radiosensitivity. The radiation protection framework will need to respond to the challenge of recurrent imaging and high individual doses. The radiation protection perspective complements the clinical perspective, and the risk to benefit analysis must account holistically for all incidental and long-term benefits and risks for patients, their clinical history and specific needs. This is a step toward the patient-centric health care.


Assuntos
Diagnóstico por Imagem , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/prevenção & controle , Doses de Radiação , Proteção Radiológica/métodos , Humanos , Monitoramento de Radiação/métodos , Radiação Ionizante , Compostos Radiofarmacêuticos , Retratamento , Fatores de Risco
12.
J Urol ; 206(3): 715-724, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33872051

RESUMO

PURPOSE: We present final 5-year outcomes of the multicenter randomized sham-controlled trial of a water vapor therapy (Rezum™) for treatment of moderate to severe lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 subjects >50 years of age with International Prostate Symptom Score ≥13, maximum flow rate ≤15 ml/second and prostate volume 30 to 80 cc were randomized and followed for 5 years. From the control arm of 61 subjects, a subset of 53 subjects requalified and after 3 months received treatment as part of the crossover group and were also followed for 5 years. The total number of vapor treatments to each lobe of the prostate was determined by length of prostatic urethra and included middle lobe treatment per physician discretion. RESULTS: Significant improvement of lower urinary tract symptoms was observed at <3 months post-thermal therapy, remaining durable through 5 years in the treatment group (International Prostate Symptom Score reduced 48%, quality of life increased 45%, maximum flow rate improved 44%, Benign Prostatic Hyperplasia Impact Index decreased 48%). Surgical re-treatment rate was 4.4% with no reports of device or procedure related sexual dysfunction or sustained de novo erectile dysfunction. Results within the crossover group were similar through 5 years. CONCLUSIONS: Minimally invasive treatment with water vapor thermal therapy provides significant and durable symptom relief as well as flow rate improvements through 5 years, with low surgical re-treatment rates and without impacting sexual function. It is a versatile therapy, providing successful treatment to obstructive lateral and middle lobes.


Assuntos
Hipertermia Induzida/métodos , Sintomas do Trato Urinário Inferior/terapia , Hiperplasia Prostática/terapia , Idoso , Estudos Cross-Over , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Seguimentos , Humanos , Hipertermia Induzida/efeitos adversos , Hipertermia Induzida/estatística & dados numéricos , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hiperplasia Prostática/complicações , Qualidade de Vida , Retratamento/estatística & dados numéricos , Índice de Gravidade de Doença , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/etiologia , Vapor , Estados Unidos
13.
Dent. press endod ; 11(1): 92-97, Jan-Apr2021. Ilus
Artigo em Inglês | LILACS | ID: biblio-1348278

RESUMO

Introdução: O laser em baixa intensidade apresenta propriedades que podem ser efetivas no tratamento endodôntico, como a capacidade reparadora, a atuação antimicrobiana e o auxílio à proliferação celular. Objetivo: Descrever, por meio do relato de um caso clínico, a ação do laser em baixa intensidade como coadjuvante na reparação óssea de uma perfuração radicular e lesão perirradicular em um elemento dentário com canais tratados, sendo realizado retratamento endodôntico apenas do canal mesiovestibular, utilizando-se hidróxido de cálcio como medicação intracanal e laser em baixa intensidade. Os demais canais não foram submetidos a retratamento, apesar de apresentarem lesão perirradicular. Resultados: O laser em baixa intensidade mostrou-se efetivo como auxiliar no processo de reparação óssea restituindo, ad integrum, o osso interradicular e as lesões perirradiculares das raízes mesial e distal após acompanhamento de 12 anos. Conclusões: O laser em baixa intensidade pode ser utilizado como coadjuvante ao tratamento de perfurações, demonstrando sucesso em longo prazo (AU).


Introduction: Low intensity laser has properties that may be effective in endodontic treatment, such as restorative capacity, antimicrobial performance and cell proliferation. Methods: This report describes the action of low intensity laser as an adjunct to bone repair of a root perforation and peri-radicular lesion in a tooth submitted to endodontic treatment, in which endodontic retreatment was performed only in the mesiobuccal canal using calcium hydroxide as intracanal medication and low level laser. The other canals were not submitted to retreatment, in spite of having peri-radicular lesions. Results: The low-intensity laser was effective as an adjunct to the bone repair process, restoring ad-integrum, interradicular bone and the peri-radicular lesions of the mesial and distal roots, after 12 years of follow-up. Conclusion: The laser at low intensity can be used as a coadjuvant to the treatment of perforations, demonstrating long-term success (AU).


Assuntos
Humanos , Tratamento do Canal Radicular , Terapêutica/métodos , Proliferação de Células , Retratamento , Terapia com Luz de Baixa Intensidade
14.
J Oral Sci ; 63(2): 163-166, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33731503

RESUMO

PURPOSE: To compare the effect of photodynamic therapy (PDT) as a procedure to complement root canal treatment (RCT), for both primary treatment and retreatment. METHODS: This was a retrospective study based on analysis of clinical records. A total of 214 teeth that had undergone RCT on either a primary or retreatment basis, with or without complementary PDT, were evaluated. For 118 teeth that met the previously established inclusion criteria, the time until healing was evaluated. Complementarily, the need for application of calcium hydroxide (CaHy) between visits and the number of visits necessary for completing the treatment were assessed. Data were analyzed using the Mann-Whitney and χ2 tests with a significance level of P < 0.05. RESULTS: Periapical radiolucency resolution was achieved at 15 ± 9.33 months in the RCT + PDT group and 20.35 ± 22.1 months in the RCT group (P = 0.07). For primary treatment, CaHy was necessary in 72.4% of the RCT cases and 16.4% of the RCT + PDT cases (P < 0.01). For retreatment cases, CaHy was used in 82.7% of the RCT cases and 17% of the RCT + PDT cases (P < 0.01). In the RCT group, more than two visits were necessary for primary treatment in 18.6% of the cases, compared with 13.10% in the RCT + PDT group (P = 0.31), whereas for retreatment, more than two visits were necessary for 64.9% and 49.1% of cases, respectively (P = 0.05). CONCLUSION: In comparison with RCT alone, teeth receiving RCT + PDT showed less variation in the time needed for periapical lesion healing, fewer cases required CaHy, and fewer cases required more than two visits to complete the treatment.


Assuntos
Cavidade Pulpar , Fotoquimioterapia , Retratamento , Estudos Retrospectivos , Tratamento do Canal Radicular , Resultado do Tratamento
15.
Ann Vasc Surg ; 71: 392-401, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32827677

RESUMO

BACKGROUND: Endovascular aneurysm repair (EVAR) using a bifurcated stent graft may involve technical challenges when aortic disease (aneurysm or dissection) consists of a length <70 mm between the inferior renal artery and aortic bifurcation or narrow aortic bifurcation that is common in asymmetric distal abdominal aortic aneurysms (AAAs) or iliac artery aneurysms (IAAs). We use EVAR with the double D technique (DDT-EVAR) for such cases, which involves straight type of stent grafts with same diameter in left and right that are deployed parallel to an aortic cuff that has been previously placed. In addition, DDT-EVAR can preserve the inferior mesenteric artery (IMA) for IAA. METHODS: DDT-EVAR was performed for 21 of 910 (2%) cases from April 2007 to April 2019 at our institution. The median patient age was 74 years (range, 52-85). Nineteen patients (90%) were men. Six patients (all saccular; 1 rupture) had AAAs, 12 had IAAs, and 3 had chronic type B aortic dissociation (TBAD) for re-entry closure. AAA and IAA had diameters of 45 mm (range, 34-71) and 34 mm (range, 25-58), respectively. An aortic cuff was used for 19 (90%) cases. Endurant II (Medtronic, Santa Rosa, CA) was used for 12 cases. The Excluder (W.L. Gore & Associates, Inc, Flagstaff, AZ) was used for 7 cases. Endurant II was used for 20 cases, and the VBX (W.L. Gore & Associates, Inc) was used for 1 case as stent-graft limbs. RESULTS: The procedural success rate was 100%. The median operative time was 146 min (range, 88-324). IMA planned for preservation was successful for all 12 cases. Type I and type III endoleaks were not observed. With TBAD, flow to the false lumen decreased or disappeared, and no complications during the hospital stay were associated with the procedure. For 2 patients whose procedure involved Endurant II stent-graft limb, limb occlusions were observed postoperatively, and reintervention was required. No other patients required additional treatment at a median follow-up of 18 months (range, 4-50). CONCLUSIONS: DDT-EVAR is a safe and straightforward technique for the treatment of distal AAA, common iliac artery aneurysm, and TBAD. It may help preserve the IMA and internal iliac artery, even when it is impossible to preserve them with a bifurcated stent graft.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Dissecção Aórtica/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Aneurisma Ilíaco/cirurgia , Stents , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Ruptura Aórtica/diagnóstico por imagem , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Aneurisma Ilíaco/diagnóstico por imagem , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/terapia , Retratamento , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
16.
J Vasc Surg ; 73(3): 856-866, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32623106

RESUMO

BACKGROUND: Endologix issued important safety updates for the AFX Endovascular AAA System in 2016 and 2018 owing to the risk of type III endoleaks. Outcomes with these devices are limited to small case series with short-term follow-up. We describe the midterm outcomes for a large cohort of patients who received an Endologix AFX or AFX2 device. STUDY DESIGN: Data from an integrated healthcare system's implant registry, which prospectively monitors all patients after endovascular aortic repair, was used for this descriptive study. Patients undergoing endovascular aortic repair with three AFX System variations (Strata [AFX-S], Duraply [AFX-D], and AFX2 with Duraply [AFX2]) were identified (2011-2017). Crude cumulative event probabilities for endoleak (types I and III), major reintervention, conversion to open, rupture, and mortality (aneurysm related and all cause) were estimated. RESULTS: Among 605 patients, 375 received AFX-S, 197 received AFX-D, and 33 received AFX2. Median follow-up for the cohort was 3.9 (interquartile range, 2.5-5.1) years. The crude 2-year incidence of overall endoleak, any subsequent reintervention or conversion, and mortality was 8.8% (95% confidence interval [CI], 6.3-12.3), 12.0% (95% CI, 9.1-15.9), and 8.8% (95% CI, 6.3-12.2) for AFX-S. Respective estimates for AFX-D were 7.9% (95% CI, 4.8-13.0), 10.6% (95% CI, 6.9-16.1), and 9.7% (95% CI, 6.3-14.7); for AFX2, they were 14.1% (95% CI, 4.7-38.2), 16.2% (95% CI, 6.4-37.7), and 21.2% (95% CI, 10.7-39.4). CONCLUSIONS: The midterm outcomes of a large U.S. patient cohort with an Endologix AFX or AFX2 System demonstrate a concerning rate of adverse postoperative events. Patients with these devices should receive close clinical surveillance to prevent device-related adverse events.


Assuntos
Aneurisma Aórtico/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Prestação Integrada de Cuidados de Saúde , Procedimentos Endovasculares/instrumentação , Idoso , Idoso de 80 Anos ou mais , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/mortalidade , Ruptura Aórtica/etiologia , Ruptura Aórtica/mortalidade , Ruptura Aórtica/terapia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Endoleak/etiologia , Endoleak/mortalidade , Endoleak/terapia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Desenho de Prótese , Sistema de Registros , Retratamento , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
18.
Clin Cancer Res ; 27(9): 2378-2382, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33288660

RESUMO

On June 15, 2020, the FDA granted accelerated approval to lurbinectedin for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Approval was granted on the basis of the clinically meaningful effects on overall response rate (ORR) and duration of response (DOR), and the safety profile observed in a multicenter, open-label, multicohort clinical trial (PM1183-B-005-14, NCT02454972), referred to as Study B-005, in patients with advanced solid tumors. The trial included a cohort of 105 patients with metastatic SCLC who had disease progression on or after platinum-based chemotherapy. The confirmed ORR determined by investigator assessment using RECIST 1.1 in the approved SCLC patient population was 35% [95% confidence interval (CI): 26-45], with a median DOR of 5.3 (95% CI: 4.1-6.4) months. The drug label includes warnings and precautions for myelosuppression, hepatotoxicity, and embryo-fetal toxicity. This is the first drug approved by the FDA in over 20 years in the second line for patients with metastatic SCLC. Importantly, this approval includes an indication for patients who have platinum-resistant disease, representing an area of particular unmet need.


Assuntos
Antineoplásicos/uso terapêutico , Carbolinas/uso terapêutico , Aprovação de Drogas , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carbolinas/farmacologia , Terapia Combinada , Gerenciamento Clínico , Avaliação Pré-Clínica de Medicamentos , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Retratamento , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration
19.
Cochrane Database Syst Rev ; 12: CD012867, 2020 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-33368143

RESUMO

BACKGROUND: A variety of minimally invasive surgical approaches are available as an alternative to transurethral resection of the prostate (TURP) for management of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Prostatic arterial embolization (PAE) is a relatively new, minimally invasive treatment approach. OBJECTIVES: To assess the effects of PAE compared to other procedures for treatment of LUTS in men with BPH. SEARCH METHODS: We performed a comprehensive search using multiple databases (The Cochrane Library, MEDLINE, Embase, LILACS, Scopus, Web of Science, and Google Scholar), trials registries, other sources of grey literature, and conference proceedings with no restrictions on language of publication or publication status, up until 25 September 2020. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs), as well as non-randomized studies (NRS, limited to prospective cohort studies with concurrent comparison groups) enrolling men over the age of 40 with LUTS attributed to BPH undergoing PAE versus TURP or other surgical interventions.  DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies for inclusion or exclusion and abstracted data from the included studies. We performed statistical analyses by using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE guidance to rate the certainty of evidence of RCTs and NRSs.  MAIN RESULTS: We found data to inform two comparisons: PAE versus TURP (six RCTs and two NRSs), and PAE versus sham (one RCT). Mean age, IPSS, and prostate volume of participants were 66 years, 22.8, and 72.8 mL, respectively. This abstract focuses on the comparison of PAE versus TURP as the primary topic of interest. PAE versus TURP We included six RCTs and two NRSs with short-term (up to 12 months) follow-up and one RCT with long-term follow-up (13 to 24 months).  Short-term follow-up: based on RCT evidence, there may be little to no difference in urologic symptom score improvement (mean difference [MD] 1.55, 95% confidence interval [CI] -0.40 to 3.50; 369 participants; 6 RCTs; I² = 75%; low-certainty evidence) measured by the International Prostatic Symptom Score (IPSS) on a scale from 0 to 35, with higher scores indicating worse symptoms. There may be little to no difference in quality of life (MD 0.16, 95% CI -0.37 to 0.68; 309 participants; 5 RCTs; I² = 56%; low-certainty evidence) as measured by the IPSS quality of life question on a scale from 0 to 6, with higher scores indicating worse quality of life between PAE and TURP, respectively. While we are very uncertain about the effects of PAE on major adverse events (risk ratio [RR] 0.71, 95% CI 0.16 to 3.10; 250 participants; 4 RCTs; I² = 26%; very low-certainty evidence), PAE may increase re-treatments (RR 3.64, 95% CI 1.02 to 12.98; 204 participants; 3 RCTs; I² = 0%; low-certainty evidence). Based on 18 re-treatments per 1000 men in the TURP group, this corresponds to 47 more (0 more to 214 more) per 1000 men undergoing PAE.   We are very uncertain about the effects on erectile function (MD -0.03, 95% CI -6.35 to 6.29; 129 participants; 2 RCTs; I² = 78%; very low-certainty evidence) measured by the International Index of Erectile Function at 5 on a scale from 1 to 25, with higher scores indicating better function. NRS evidence when available yielded similar results. Based on evidence from NRS, PAE may reduce the occurrence of ejaculatory disorders (RR 0.51, 95% CI 0.35 to 0.73; 260 participants; 1 NRS; low-certainty evidence). Longer-term follow-up: based on RCT evidence, we are very uncertain about the effects of PAE on urologic symptom scores (MD 0.30, 95% CI -3.17 to 3.77; 95 participants; very low-certainty evidence) compared to TURP. Quality of life may be similar (MD 0.20, 95% CI -0.49 to 0.89; 95 participants; low-certainty evidence). We are also very uncertain about major adverse events (RR 1.96, 95% CI 0.63 to 6.13; 107 participants; very low-certainty evidence). We did not find evidence on erectile function and ejaculatory disorders. Based on evidence from NRS, PAE may increase re-treatment rates (RR 1.51, 95% CI 0.43 to 5.29; 305 participants; low-certainty evidence); based on 56 re-treatments per 1000 men in the TURP group. this corresponds to 143 more (25 more to 430 more) per 1000 men in the PAE group.  AUTHORS' CONCLUSIONS: Compared to TURP up to 12 months (short-term follow-up), PAE may provide similar improvement in urologic symptom scores and quality of life. While we are very uncertain about major adverse events, PAE may increase re-treatment rates. We are uncertain about erectile function, but PAE may reduce ejaculatory disorders. Longer term (follow-up of 13 to 24 months), we are very uncertain as to how both procedures compare with regard to urologic symptom scores, but quality of life appears to be similar. We are very uncertain about major adverse events but PAE may increase re-treatments. We did not find longer term evidence on erectile function and ejaculatory disorders. Certainty of evidence for the main outcomes of this review was low or very low, signalling that our confidence in the reported effect size is limited or very limited, and that this topic should be better informed by future research.


Assuntos
Embolização Terapêutica/métodos , Sintomas do Trato Urinário Inferior/terapia , Próstata/irrigação sanguínea , Hiperplasia Prostática/complicações , Ressecção Transuretral da Próstata , Idoso , Artérias , Ejaculação , Embolização Terapêutica/efeitos adversos , Humanos , Masculino , Ereção Peniana , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Retratamento/estatística & dados numéricos , Disfunções Sexuais Fisiológicas/etiologia , Ressecção Transuretral da Próstata/efeitos adversos , Resultado do Tratamento
20.
Molecules ; 25(23)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33255641

RESUMO

When the first- and second-line therapeutics used to treat neuropathic pain (NP) fail to induce efficient analgesia-which is estimated to relate to more than half of the patients-opioid drugs are prescribed. Still, the pathological changes following the nerve tissue injury, i.a. pronociceptive neuropeptide systems activation, oppose the analgesic effects of opiates, enforcing the use of relatively high therapeutic doses in order to obtain satisfying pain relief. In parallel, the repeated use of opioid agonists is associated with burdensome adverse effects due to compensatory mechanisms that arise thereafter. Rational design of hybrid drugs, in which opioid ligands are combined with other pharmacophores that block the antiopioid action of pronociceptive systems, delivers the opportunity to ameliorate the NP-oriented opioid treatment via addressing neuropathological mechanisms shared both by NP and repeated exposition to opioids. Therewith, the new dually acting drugs, tailored for the specificity of NP, can gain in efficacy under nerve injury conditions and have an improved safety profile as compared to selective opioid agonists. The current review presents the latest ideas on opioid-comprising hybrid drugs designed to treat painful neuropathy, with focus on their biological action, as well as limitations and challenges related to this therapeutic approach.


Assuntos
Analgésicos Opioides/química , Analgésicos Opioides/farmacologia , Neuralgia/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Animais , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Estrutura Molecular , Neuralgia/etiologia , Neuralgia/metabolismo , Manejo da Dor , Receptores Opioides/metabolismo , Retratamento , Relação Estrutura-Atividade , Resultado do Tratamento
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