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1.
Am J Med Genet A ; 194(2): 195-202, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37774117

RESUMO

Fetuses with RASopathies can have a wide variety of anomalies including increased nuchal translucency, hydrops fetalis, and structural anomalies (typically cardiac and renal). There are few reports that describe prenatal-onset craniosynostosis in association with a RASopathy diagnosis. We present clinical and molecular characteristics of five individuals with RASopathy and craniosynostosis. Two were diagnosed with craniosynostosis prenatally, 1 was diagnosed as a neonate, and 2 had evidence of craniosynostosis noted as neonates without formal diagnosis until later. Two of these individuals have Noonan syndrome (PTPN11 and KRAS variants) and three individuals have Cardiofaciocutaneous syndrome (KRAS variants). Three individuals had single suture synostosis and two had multiple suture involvement. The most common sutures involved were sagittal (n = 3), followed by coronal (n = 3), and lambdoid (n = 2) sutures. This case series confirms craniosynostosis as one of the prenatal findings in individuals with RASopathies and emphasizes the importance of considering a RASopathy diagnosis in fetuses with multiple anomalies in combination with craniosynostosis.


Assuntos
Craniossinostoses , Cardiopatias Congênitas , Síndrome de Noonan , Recém-Nascido , Feminino , Humanos , Gravidez , Proteínas Proto-Oncogênicas p21(ras)/genética , Craniossinostoses/diagnóstico , Craniossinostoses/genética , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Ultrassonografia Pré-Natal
2.
J Oncol Pharm Pract ; : 10781552241237750, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454628

RESUMO

OBJECTIVE: New drugs developed for SARS-CoV-2 infection, such as nirmatrelvir/ritonavir (NMV/r), represent a potential for oncohematology patients, but also pose a challenge in managing the potential clinically relevant drug-drug interactions (pDDIs) that may arise. The aim of this study is to assess the frequency, severity, and pharmacist detection of pDDIs. METHODS: This prospective, observational, study spanned 8 months, involving 42 oncohematology patients prescribed NMV/r in a tertiary-level hospital. A Board Certified oncology pharmacist assessed pDDIs using three databases and made recommendations to prescribing physicians. Linear and logistic regression analyses were employed to explore the relationship between prescribed drugs and pDDIs. RESULTS: Clinically relevant pDDIs were detected in 76.2% of patients, with 18.1% of all medications involved in drug-drug interactions (DDIs). The most common drugs implicated were atorvastatin and imatinib. Micromedex® identified 63.3% of interactions as major severity, while Lexicomp® and University of Liverpool classifications were less restrictive. Pharmacists prevented most DDIs from reaching patients through different interventions, including treatment monitoring (44.2%), discontinuation (36.5%), and dose reduction (17.3%). CONCLUSION: This study highlights the high prevalence of clinically significant pDDIs in oncohematology patients receiving NMV/r for COVID-19. Pharmacists, as integral members of the healthcare team, played a crucial role in detecting, categorizing, and mitigating these interactions. The results underscore the need for comprehensive studies to evaluate the impact of pharmacist-led interventions in optimizing drug therapy and enhancing patient safety in this vulnerable population.

3.
Rev Gastroenterol Peru ; 44(1): 26-34, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38734909

RESUMO

INTRODUCTION: Attempts have been made to identify the genetic factors related to susceptibility to inflammatory bowel disease (IBD), and the current conclusions are in favor of a complex pathology model, without a clear hereditary pattern. OBJECTIVE: To perform phenotypic and genotypic characterization of patients with IBD in Colombian population and to describe its possible association with predisposition. MATERIALS AND METHODS: case series, 16 patients with IBD according to clinical and pathological criteria, onset of gastrointestinal symptoms after 18 years of age. All had pre-test genetic counseling and family trees of at least three generations were made. Also, genotyping, using a multi-gene panel that included genes related to IBD and some autoimmune disorders. Finally, a genomic analysis of variants was performed. RESULTS: 9 women and 7 men, with mean age of diagnosis of IBD of 35 years, and gastrointestinal symptoms appearance of 32 years. 11/16 (68.75%) required biological therapy. 10/16 (62.5%) were refractory to standard therapy. 3/16 (18.75%) had positive family history of IBD. 100% cases presented at least one single nucleotide polymorphism related to IBD risk in more than one gene. The genes most related to ulcerative colitis (UC) were CD48, CD6, and TYK2 for UC, and CD6 and ITGAM for Crohn's disease. The most frequent gene was CD6. It was found presence of up to 5 genes in 3/16 (18.75%), 4 in 3/16 (18.75%), and three in 5/16 (31.25%). CONCLUSION: In IBD there is the presence of genetic variants with associated predisposition, but without confirmed pathogenicity, and whose sum seems to contribute to its pathophysiology.


Assuntos
Predisposição Genética para Doença , Genótipo , Fenótipo , Humanos , Colômbia/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Doenças Inflamatórias Intestinais/genética , Adolescente , Doença de Crohn/genética , Doença de Crohn/epidemiologia , Colite Ulcerativa/genética
4.
Sleep Breath ; 27(6): 2181-2189, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36973595

RESUMO

PURPOSE: Obstructive sleep apnoea (OSA) and cardiac conduction disorders are pathologies with a rising prevalence due to increased life expectancy. Upper airway patency is affected by environmental factors that may be associated with seasonal periods. The ability to record the degree of nocturnal apnoea on a daily basis may provide a more accurate picture of seasonal variability. METHODS: This study used an observational, cross-sectional design recruiting consecutive patients with Sorin/Livanova/Microport® pacemakers. The study assessed the seasonal influence on the daily degree of nocturnal apnoea over a minimum period of 180 days. The respiratory events were recorded using a pacemaker-integrated detection algorithm based on transthoracic impedance variation. A generalised linear repeated measure mixed model was used to study the seasonal effect. RESULTS: A sample of 101 subjects with a mean of 227 valid nights was compiled. Summer was associated with higher RDI (respiratory disturbance index) values and winter with lower values. The mean daily RDI ratio in summer was 1.099 times higher than in winter. CONCLUSIONS: Slight seasonal influences on the degree of nocturnal apnoea were detected through the daily observation of an unselected sample of pacemaker wearers. The degree of apnoea is higher in warmer months and lower in colder months.


Assuntos
Marca-Passo Artificial , Síndromes da Apneia do Sono , Humanos , Estudos Transversais , Estações do Ano , Polissonografia , Síndromes da Apneia do Sono/diagnóstico
5.
J Neuroeng Rehabil ; 20(1): 38, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-37016408

RESUMO

TRIAL OBJECTIVE: To verify whether conventional rehabilitation combined with specific virtual reality is more effective than conventional therapy alone in restoring hand motor function and muscle tone after stroke. TRIAL DESIGN: This prospective single-blind randomized controlled trial compared conventional rehabilitation based on physiotherapy and occupational therapy (control group) with the combination of conventional rehabilitation and specific virtual reality technology (experimental group). Participants were allocated to these groups in a ratio of 1:1. The conventional rehabilitation therapists were blinded to the study, but neither the participants nor the therapist who applied the virtual reality-based therapy could be blinded to the intervention. PARTICIPANTS: Forty-six patients (43 of whom completed the intervention period and follow-up evaluation) were recruited from the Neurology and Rehabilitation units of the Hospital General Universitario of Talavera de la Reina, Spain. INTERVENTION: Each participant completed 15 treatment sessions lasting 150 min/session; the sessions took place five consecutive days/week over the course of three weeks. The experimental group received conventional upper-limb strength and motor training (100 min/session) combined with specific virtual reality technology devices (50 min/session); the control group received only conventional training (150 min/session). RESULTS: As measured by the Ashworth Scale, a decrease in wrist muscle tone was observed in both groups (control and experimental), with a notably larger decrease in the experimental group (baseline mean/postintervention mean: 1.22/0.39; difference between baseline and follow-up: 0.78; 95% confidence interval: 0.38-1.18; effect size = 0.206). Fugl-Meyer Assessment scores were observed to increase in both groups, with a notably larger increase in the experimental group (total motor function: effect size = 0.300; mean: - 35.5; 95% confidence interval: - 38.9 to - 32.0; wrist: effect size = 0.290; mean: - 5.6; 95% confidence interval: - 6.4 to - 4.8; hand: effect size = 0.299; mean: - -8.9; 95% confidence interval: - 10.1 to - 7.6). On the Action Research Arm Test, the experimental group quadrupled its score after the combined intervention (effect size = 0.321; mean: - 32.8; 95% confidence interval: - 40.1 to - 25.5). CONCLUSION: The outcomes of the study suggest that conventional rehabilitation combined with a specific virtual reality technology system can be more effective than conventional programs alone in improving hand motor function and voluntary movement and in normalizing muscle tone in subacute stroke patients. With combined treatment, hand and wrist functionality and motion increase; resistance to movement (spasticity) decreases and remains at a reduced level. TRIALS REGISTRY: International Clinical Trials Registry Platform: ISRCTN27760662 (15/06/2020; retrospectively registered).


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Terapia de Exposição à Realidade Virtual , Realidade Virtual , Humanos , Método Simples-Cego , Estudos Prospectivos , Recuperação de Função Fisiológica , Resultado do Tratamento , Extremidade Superior
6.
Int Orthop ; 46(4): 677-685, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34988621

RESUMO

PURPOSE: Microencapsulation techniques have allowed the addition of rifampicin to bone cement, but its in vivo efficacy has not been proven. The aim of our study is to determine the superiority of cement containing gentamicin and rifampicin microcapsules in the treatment of PJI versus cement exclusively containing gentamicin. METHODS: An S. aureus PJI was induced in 15 NZW rabbits. A week after inoculation, the first stage of replacement was carried out, and the animals were divided into two groups: group R received a spacer containing gentamicin and rifampicin microcapsules, and group C received a spacer containing gentamicin. Intra-articular release curve of rifampicin and infection and toxicity markers were monitored for four weeks post-operatively, when microbiological analysis was performed. RESULTS: The microbiological cultures showed a significantly lower growth of S. aureus in soft tissue (2.3·104 vs 0; p = 0.01) and bone (5.7·102 vs 0; p = 0.03) in the group with rifampicin microcapsules. No differences were found in systemic toxicity markers. Rifampicin release from the cement spacer showed higher concentrations than the staphylococcal MIC throughout the analysis. CONCLUSION: The in vivo analyses demonstrated the superiority of cement containing gentamicin and rifampicin microcapsules versus the isolated use of gentamicin in the treatment of PJI in the rabbit model without serious side effects due to the systemic absorption of rifampicin. Given the increasing incidence of staphylococci-related PJI, the development of new strategies for intra-articular administration of rifampicin for its treatment has a high clinical impact.


Assuntos
Infecções Relacionadas à Prótese , Rifampina , Animais , Antibacterianos/uso terapêutico , Cimentos Ósseos/uso terapêutico , Humanos , Infecções Relacionadas à Prótese/microbiologia , Coelhos , Rifampina/uso terapêutico , Staphylococcus aureus
7.
Age Ageing ; 50(2): 370-379, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33068106

RESUMO

BACKGROUND: The accessibility, versatility and motivation provided by virtual reality technology (VRT) have fostered its rapid expansion as a rehabilitation technique to improve functional mobility. The aim of this study was to investigate the effectiveness of rehabilitation programmes using VRT, specific virtual reality technology (VRT-S) and non-specific virtual reality technology (VRT-NS), to improve functional mobility in individuals aged >60 years versus conventional treatment (CT) or no intervention. METHODS: Nine databases (Cochrane Library, Scopus, PEDro, Medline, CSIC, Web of Science, OT Seeker, NGCH and CINAHL) were searched to identify randomised trials up to December 2019. Results of clinical trials that used VRT-S and VRT-NS in rehabilitation were combined, using a random effects model with inverse variance weighting of the studies. GRADE was used to assess the quality of evidence. The protocol was registered in PROSPERO: CRD42019131630. Overall, there was moderate quality of evidence for the functional mobility results, which means that the estimate of effect is likely to change. RESULTS: Sixteen of the 18 studies selected (n = 568) provided data for the subgroup meta-analysis. VRT-NS was more effective in improving functional mobility than no intervention [standardised mean difference (SMD) = -1.02; 95% confidence interval (CI) -1,91 to -0,14). VRT-NS was also more effective than CT in improving resistance in ambulation (SMD = -1.20; 95% CI -1.93 to 0.46). No significant differences were found between VRT-S and CT or no intervention. Programmes in which >18 sessions were applied were more beneficial (SMD = -0.89; 95% CI -1.71 to -0.08; <0.001) than programmes with ≤18 sessions (SMD = 0.04; 95% CI -0.51 to 0.59) versus no intervention. CONCLUSIONS: Our results suggest that VRT is an effective intervention for improving functional mobility in older persons compared with CT. VRT-NS proved to be more effective than VRT-S. However, these results are still not conclusive due to the low methodological quality of the studies. Thus, new studies and analyses are required.


Assuntos
Realidade Virtual , Idoso , Idoso de 80 Anos ou mais , Humanos , Tecnologia , Caminhada
8.
Int J Mol Sci ; 21(18)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32961930

RESUMO

CD4+T-lymphocytes are relevant in the pathogenesis of rheumatoid arthritis (RA), however, their potential involvement in early RA remains elusive. Methotrexate (MTX) is a commonly used disease-modifying antirheumatic drug (DMARD), but its mechanism has not been fully established. In 47 new-onset DMARD-naïve RA patients, we investigated the pattern of IFNγ, IL-4 and IL-17A expression by naïve (TN), central (TCM), effector memory (TEM) and effector (TE) CD4+ subsets; their STAT-1, STAT-6 and STAT-3 transcription factors phosphorylation, and the circulating levels of IFNγ, IL-4 and IL-17. We also studied the RA patients after 3 and 6 months of MTX treatment and according their clinical response. CD4+T-lymphocyte subsets and cytokine expression were measured using flow cytometry. New-onset DMARD-naïve RA patients showed a significant expansion of IL-17A+, IFNγ+ and IL-17A+IFNγ+ CD4+T-lymphocyte subsets and increased intracellular STAT-1 and STAT-3 phosphorylation. Under basal conditions, nonresponder patients showed increased numbers of circulating IL-17A producing TN and TMC CD4+T-lymphocytes and IFNγ producing TN, TCM, TEM CD4+T-lymphocytes with respect to responders. After 6 months, the numbers of CD4+IL-17A+TN remained significantly increased in nonresponders. In conclusion, CD4+T-lymphocytes in new-onset DMARD-naïve RA patients show IL-17A and IFNγ abnormalities in TN, indicating their relevant role in early disease pathogenesis. Different patterns of CD4+ modulation are identified in MTX responders and nonresponders.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Linfócitos T CD4-Positivos/metabolismo , Citocinas/sangue , Metotrexato/uso terapêutico , Adulto , Artrite Reumatoide/fisiopatologia , Linfócitos T CD4-Positivos/imunologia , Células Cultivadas , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Interferon gama/sangue , Interferon gama/metabolismo , Interleucina-17/sangue , Interleucina-17/metabolismo , Interleucina-4/sangue , Interleucina-4/metabolismo , Masculino , Pessoa de Meia-Idade , Fosforilação , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT6/metabolismo
9.
Mod Rheumatol ; 30(6): 1016-1024, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31599659

RESUMO

Objectives: This study analyzed sleep quality in fibromyalgia (FM) and systemic lupus erythematosus (SLE) and explored its relationship with other clinical and psychological manifestations.Methods: Twenty women with FM, 19 women with SLE and 22 healthy women participated in the study. Subjective sleep quality, fatigue, pain, depression and anxiety were evaluated with self-reports, and objective sleep measures were obtained with actigraphy. Comparisons were analyzed with Chi-square, Kruskal-Wallis's H and Mann-Whitney's U tests. Relationships between measurements were analyzed with Spearman's correlation coefficients.Results: Subjective sleep quality was altered in the FM and SLE groups compared to the control group (15.53 ± 3.27, 8.47 ± 3.20, 4.91 ± 2.79, p < .05, respectively). FM and SLE patients reported higher levels of pain (22.65 ± 9.87, 10.21 ± 9.93, 2.30 ± 3.096, p < .05), fatigue (4.67 ± 0.37, 3.59 ± 3.04, 2.33 ± 0.59, p < .05) and depressive symptoms (9.90 ± 3.78, 4.53 ± 3.04, 4.17 ± 3.95, p < .05) than controls, respectively. Worse subjective quality of sleep was associated with higher pain intensity and more depressive symptoms in FM and SLE. Actigraphy measures showed that FM patients spent more time in bed than subjects in the remaining groups.Conclusion: Sleep deterioration is related to more pain and depressive symptoms in FM and SLE. Addressing sleep disturbances may improve not only sleep quality but also depressive symptoms and pain.


Assuntos
Ansiedade/epidemiologia , Fadiga/epidemiologia , Fibromialgia/psicologia , Lúpus Eritematoso Sistêmico/psicologia , Sono , Adulto , Ansiedade/etiologia , Fadiga/etiologia , Feminino , Fibromialgia/complicações , Humanos , Lúpus Eritematoso Sistêmico/complicações , Pessoa de Meia-Idade
10.
Am J Med Genet A ; 179(4): 608-614, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30762279

RESUMO

RASopathies are a group of developmental disorders caused by pathogenic variants in the RAS-MAPK pathway. Cardiomyopathy is a major feature of this group of disorders, specifically hypertrophic cardiomyopathy (HCM). HCM can be the first presenting feature in individuals with RASopathies. We conducted a retrospective study of all individuals who have had a cardiomyopathy gene panel ordered through our institution to determine the prevalence of pathogenic or likely pathogenic variants in RAS pathway genes in individuals with cardiomyopathy. We evaluated variants in the following genes: BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NF1, NRAS, PTPN11, RAF1, SHOC2, and SOS1. We reviewed 74 cases with cardiomyopathy, including 32 with HCM, 24 with dilated cardiomyopathy (DCM), nine with both left ventricular noncompaction (LVNC) and DCM, four with LVNC only, two with arrhythmogenic right ventricular cardiomyopathy (ARVC) and three with unspecified cardiomyopathy. We identified four patients (5.41%) with pathogenic or likely pathogenic variants in HRAS, PTPN11 and RAF1 (two individuals). Indication for testing for all four individuals was HCM. The prevalence of pathogenic or likely pathogenic variants in RASopathy genes in our HCM patient cohort is 12.5% (4/32). We conclude that the RASopathy genes should be included on multi-gene panels for cardiomyopathy to increase diagnostic yield for individuals with HCM.


Assuntos
Cardiomiopatias/genética , Cardiomiopatias/patologia , Mutação , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas ras/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Estudos Retrospectivos , Adulto Jovem
11.
Langmuir ; 34(9): 3146-3157, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29411980

RESUMO

The process of equilibration of the tetradecane-water interface in the presence of sodium hexadecane-benzene sulfonate is studied using intensive atomistic molecular dynamics simulations. Starting as an initial point with all of the surfactants at the interface, it is obtained that the equilibration time of the interface (several microseconds) is orders of magnitude higher than previously reported simulated times. There is strong evidence that this slow equilibration process is due to the aggregation of surfactants molecules on the interface. To determine this fact, temporal evolution of interfacial tension and interfacial formation energy are studied and their temporal variations are correlated with cluster formation. To study cluster evolution, the mean cluster size and the probability that a molecule of surfactant chosen at random is free are obtained as a function of time. Cluster size distribution is estimated, and it is observed that some of the molecules remain free, whereas the rest agglomerate. Additionally, the temporal evolution of the interfacial thickness and the structure of the surfactant molecules on the interface are studied. It is observed how this structure depends on whether the molecules agglomerate or not.

13.
Pharmaceutics ; 16(5)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38794247

RESUMO

Nanomedicine is the application of nanotechnology to achieve innovations in healthcare and involves the engineering of systems at the nanoscale (particle size < 1000 nm) with the aim of improving drug delivery [...].

14.
Int J Pharm ; 661: 124468, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39013533

RESUMO

Cannabidiol (CBD) is the main non-psychotropic cannabinoid. It has attracted a great deal of interest in the treatment of several diseases such as inflammatory disorders and cancer. Despite its promising clinical interest, its administration is very challenging. In situ forming implants (ISFIs) could be a simple and cheap strategy to administer CBD while obtaining a prolonged effect with a single administration. This work aims to design, develop, and characterize for the first time ISFIs for the parenteral administration of CBD with potential application in cancer disease. Formulations made of PLGA-502, PLGA-502H, and PLA-202 in NMP or DMSO and PLA-203 in DMSO at a polymer concentration of 0.25 mg/µL and loaded with CBD at a drug: polymer ratio of 2.5:100 and 5:100 (w/w) were developed. The formulations prepared with NMP exhibited a faster drug release. CBD implants elaborated with PLGA-502 and DMSO with the highest CBD: polymer ratio showed the most suitable drug release for one month. This formulation was successfully formed in ovo onto the chorioallantoic chick membrane without exhibiting signs of toxicity and exhibited a superior antiangiogenic activity than CBD in solution administered at the same doses. Consequently, implants made of PLGA-502 and DMSO represent a promising strategy to effectively administer CBD subcutaneously as combination therapy in cancer disease.


Assuntos
Canabidiol , Liberação Controlada de Fármacos , Poliésteres , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Animais , Canabidiol/administração & dosagem , Canabidiol/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Poliésteres/química , Implantes de Medicamento , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Dimetil Sulfóxido/química , Dimetil Sulfóxido/administração & dosagem , Portadores de Fármacos/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
15.
Int J Clin Pharm ; 46(2): 382-389, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38112892

RESUMO

BACKGROUND: Clinical trials of atezolizumab for locally advanced or metastatic urothelial bladder cancer (mUBC) report controversial efficacy data. Furthermore, real-world evidence about this use is limited. AIM: We aimed to evaluate the effectiveness of atezolizumab in a real-world population with mUBC, to explore effectiveness with regard to selected poor prognostic criteria such as performance status by Eastern Oncology Cooperative Group (ECOG), hemoglobin levels and liver metastases, and to determine the safety profile of atezolizumab. METHOD: Multicenter, retrospective real-world study including previously treated mUBC patients who received atezolizumab. The primary endpoint was overall survival (OS). Additionally, progression-free survival (PFS), best response reached and safety data were analyzed. A descriptive analysis was performed, while OS and PFS were estimated by Kaplan-Meier method. RESULTS: A total of 185 patients (84.9% men, median age 69 years) were included. Median PFS was 4.8 months [95% confidence interval (CI) 3.6-6.0], and median OS was 20.0 months (95% CI 11.8-28.5), with an objective response rate of 28.1%. OS was higher for patients with ECOG 0-1 versus 2-3 [24.5 months (95% CI 14.5-34.6) vs. 5.2 (95% CI 4.4-6.0), p = 0.004]; and for patients without liver metastases [25.4 months (95% CI 16.2-34.6) vs. 6.4 months (95% CI 4.0-8.1), p = 0.006]. Regarding hemoglobin levels, no survival differences were detected. Adverse events were registered in 55.1% of patients. CONCLUSION: In a real-world population with previously treated mUBC, atezolizumab seems to provide clinically relevant benefit, which is even higher for patients with ECOG 0-1 and without liver metastases, with an acceptable safety profile.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Neoplasias Hepáticas , Neoplasias da Bexiga Urinária , Masculino , Humanos , Idoso , Feminino , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Neoplasias Hepáticas/tratamento farmacológico , Hemoglobinas , Protocolos de Quimioterapia Combinada Antineoplásica
16.
Drug Deliv Transl Res ; 14(4): 959-969, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37824041

RESUMO

Cannabidiol (CBD) has become a highly attractive entity in therapeutics. However, its low aqueous solubility, instability and handling problems limit the development of effective CBD formulations. Subcutaneously administered CBD-loaded polycaprolactone microparticles (MP) represent an interesting strategy to overcome these challenges. This work focuses on evaluating the pharmacokinetics of CBD formulated in polymer microparticles for subcutaneous administration and characterising its release. The mean release time (MRLT) parameter is used to compare the release of CBD from two microparticle formulations in vitro and in a mouse model. After the administration of CBD in solution, a bicompartmental distribution is observed due to the extensive diffusion to the brain, being the brain/blood AUC ratio 1.29. The blood and brain mean residence time (MRT) are 0.507 ± 0.04 and 0.257 ± 0.0004 days, respectively. MP prepared with two drug/polymer ratios (15/150-MP and 30/150-MP) are designed, showing similar in vitro dissolution profiles (similarity factor (f2) is 63.21), without statistically significant differences between MRLTin vitro values (4.68 ± 0.63 and 4.32 ± 0.05 days). However, considerable differences in blood and brain profiles between both formulations are detected. The blood and brain MRT values of 15/150-MP are 6.44 ± 0.3 days and 6.15 ± 0.25 days, respectively, whereas significantly lower values 3.91 ± 0.29 days and 2.24 ± 0.64 days are obtained with 30/150-MP. The extended release of CBD during 10 days after a single subcutaneous administration is achieved.


Assuntos
Canabidiol , Camundongos , Animais , Canabidiol/farmacocinética , Poliésteres , Composição de Medicamentos , Polímeros , Administração Oral
17.
Musculoskelet Sci Pract ; 72: 103123, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38905971

RESUMO

OBJECTIVE: To gain insight into the emotions, cognitions, and behaviours experienced by people with chronic low back pain (CLBP) undergoing invasive treatment in a pain unit. DESIGN: A cross-sectional qualitative study based on individual interviews. This study included patient involvement in its design and development. METHODS: An interpretative phenomenological approach was adopted to understand the multidimensional experience of patients. The interview script was a translated, adapted, and expanded version of the one proposed by Cognitive and Functional Therapy. A mixed coding method was applied to structure the interviews. Three themes were created, with the three most frequently reported emotions, cognitions, and behaviours as subthemes. A patient with CLBP approved the initial protocol and the aim of the study. Subsequently, the patient contributed questions to the interview script, checked the coding process, and approved the final version of the manuscript. RESULTS: Twenty-two patients undergoing epidural infiltrations in a pain unit were interviewed. (i)"Fears", (ii)"Frustration", and (iii)"Worry" were the three most commonly expressed emotions. Cognitions related to (i)"Pain predictability", (ii)"Pain description and perception", and (iii)"Pain interference/disability" were also widely reported. The theme "Behaviours" was composed of the following subthemes: (i)"Strategies for managing symptoms", (ii)"Social behaviours", and (iii)"Strategies for coping with daily tasks". Noteworthily, cognitions related to the (i)"Diagnosis", (ii)"Health system attention", and (iii)"Medical prescriptions" arose from questions provided by patient involvement. CONCLUSION: Patients with CLBP expressed a wide variety of emotions, cognitions, and behaviours that must be considered by health professionals with the goal of providing the best patient-centred care.


Assuntos
Dor Crônica , Cognição , Emoções , Dor Lombar , Pesquisa Qualitativa , Humanos , Dor Lombar/psicologia , Dor Lombar/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Adulto , Dor Crônica/psicologia , Dor Crônica/terapia , Idoso , Participação do Paciente/psicologia
18.
Nutrients ; 16(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674912

RESUMO

BACKGROUND: Hip fractures are prevalent among older people, often leading to reduced mobility, muscle loss, and bone density decline. Malnutrition exacerbates the prognosis post surgery. This study aimed to evaluate the impact of a 12-week regimen of a high-calorie, high-protein oral supplement with ß-hydroxy-ß-methylbutyrate (HC-HP-HMB-ONS) on nutritional status, daily activities, and compliance in malnourished or at-risk older patients with hip fractures receiving standard care. SUBJECTS AND METHODS: A total of 270 subjects ≥75 years of age, residing at home or in nursing homes, malnourished or at risk of malnutrition, and post hip fracture surgery, received HC-HP-HMB-ONS for 12 weeks. Various scales and questionnaires assessed outcomes. RESULTS: During the 12 weeks of follow-up, 82.8% consumed ≥75% of HC-HP-HMB-ONS. By week 12, 62.4% gained or maintained weight (+0.3 kg), 29.2% achieved normal nutritional status (mean MNA score +2.8), and 46.8% improved nutritional status. Biochemical parameters improved significantly. Subjects reported good tolerability (mean score 8.5/10), with 87.1% of healthcare providers concurring. CONCLUSIONS: The administration of HC-HP-HMB-ONS markedly enhanced nutritional status and biochemical parameters in older hip-fracture patients, with high compliance and tolerability. Both patients and healthcare professionals expressed satisfaction with HC-HP-HMB-ONS.


Assuntos
Suplementos Nutricionais , Fraturas do Quadril , Desnutrição , Estado Nutricional , Valeratos , Humanos , Idoso , Masculino , Feminino , Estudos Prospectivos , Idoso de 80 Anos ou mais , Desnutrição/etiologia , Valeratos/administração & dosagem , Dieta Rica em Proteínas , Administração Oral , Ingestão de Energia , Proteínas Alimentares/administração & dosagem , Resultado do Tratamento
19.
Healthcare (Basel) ; 12(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338223

RESUMO

Stroke is the third leading cause of disability in the world, and effective rehabilitation is needed to improve lost functionality post-stroke. In this regard, robot-assisted therapy (RAT) and transcranial direct current stimulation (tDCS) are promising rehabilitative approaches that have been shown to be effective in motor recovery. In the past decade, they have been combined to study whether their combination produces adjuvant and greater effects on stroke recovery. The aim of this study was to estimate the effectiveness of the combined use of RATs and tDCS in the motor recovery of the upper extremities after stroke. After reviewing 227 studies, we included nine randomised clinical trials (RCTs) in this study. We analysed the methodological quality of all nine RCTs in the meta-analysis. The analysed outcomes were deficit severity, hand dexterity, spasticity, and activity. The addition of tDCS to RAT produced a negligible additional benefit on the effects of upper limb function (SMD -0.09, 95% CI -0.31 to 0.12), hand dexterity (SMD 0.12, 95% CI -0.22 to 0.46), spasticity (SMD 0.04, 95% CI -0.24 to 0.32), and activity (SMD 0.66, 95% CI -1.82 to 3.14). There is no evidence of an additional effect when adding tDCS to RAT for upper limb recovery after stroke. Combining tDCS with RAT does not improve upper limb motor function, spasticity, and/or hand dexterity. Future research should focus on the use of RAT protocols in which the patient is given an active role, focusing on the intensity and dosage, and determining how certain variables influence the success of RAT.

20.
Curr Pain Headache Rep ; 17(7): 345, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23715945

RESUMO

Fibromyalgia (FM) is a debilitating rheumatic disorder characterized mainly by the presence of continual and widespread musculoskeletal pain, in addition to other disturbing symptoms. There is inconsistent evidence about the effectiveness of the treatments developed so far, making FM a chronic disease that is difficult to treat. The aim of this literature review was to analyze the empirical studies about psychological treatment of FM that have been published over the last twenty years. We conducted a literature search of studies published between 1990 and 2012 using Medline and PsycINFO in the Ovid and ProQuest platforms and hand searching. In total, 58 original studies were identified. The present review presents a comprehensive analysis of the main characteristics of these studies and a description of the interventions developed in order to improve FM symptoms. The most used intervention modality was group treatment with a cognitive-behavioral approach. We also found intensive and remote treatments as well as multimodal therapy, hypnosis, cognitive-behavioral therapy for insomnia, behavioral therapies, mind-body-based techniques, and biofeedback components. Finally, we discuss the clinical relevance of addressing the symptoms of patients with FM and its scientific validation.


Assuntos
Terapia Comportamental/métodos , Dor Crônica/terapia , Fibromialgia/psicologia , Fibromialgia/terapia , Distúrbios do Início e da Manutenção do Sono/terapia , Biorretroalimentação Psicológica , Dor Crônica/psicologia , Terapia Cognitivo-Comportamental/métodos , Terapia Combinada , Feminino , Humanos , Hipnose , Masculino , Psicoterapia de Grupo/métodos , Distúrbios do Início e da Manutenção do Sono/psicologia , Espanha/epidemiologia , Resultado do Tratamento
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