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1.
J Postgrad Med ; 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37555423

RESUMO

In the present study patients with previously diagnosed MRI-negative temporal lobe epilepsy (TLE) on long-term video electroencephalography (VEEG) monitoring were re-evaluated with high resolution 3T MRI brain to look out for a skull base temporal lobe encephalocoele (TE). A total of 234 VEEGs were analyzed. TLE had been diagnosed in 104 patients based on semiology, ictal, interictal EEG data, and brain positron emission tomography (PET) studies. Of these, 99 patients had temporal lobe abnormality (78 had mesial temporal sclerosis, 8 had tumor, 3 had focal cortical dysplasia, and 10 had mixed pathology). Out of the five 1.5T MRI-negative TLE patients, two patients were diagnosed with TE on subsequent 3T MRI brain scans and one patient underwent electrocorticography-guided tailored resection for complete removal of epileptogenic tissue; with Engels class I seizure freedom at one year follow-up. We propose that TE should be carefully searched for, as a cause of refractory TLE, using high-resolution MRI sequences.

2.
J Psychoactive Drugs ; 55(2): 213-223, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35348049

RESUMO

Background Opioid use disorder (OUD), a relapsing-remitting chronic medical disease, accounts for a sizable proportion of all-cause adult inpatient stays. We evaluated the incidence and predictors of any and multiple readmissions to inpatient care for OUD. Methods This retrospective, register-based cohort study assessed consecutive patients with OUD admitted to a federally-funded inpatient service of an addiction treatment center in North India between January 2007 and December 2014. Binary logistic regression was used to determine independent readmission predictors based on demographic, clinical, and treatment variables that significantly differed in bivariate analysis. Results Among 908 patients, 306 (33.7%) and 106 (11.7%) had any and multiple readmissions, respectively. Injection drug use (Odds ratio [OR] 2.92, 95% confidence interval [CI] 1.90-4.49), comorbid severe mental illness (OR 2.80, 95% CI 1.42-5.55) and common mental disorder (OR 3.4 95% CI 1.65-6.95), antagonist treatment (OR 1.6 95% CI 1.14-2.27), and urban residence (OR 1.38 95% CI 1.01-1.90) increased odds of readmission. 'Improved' discharge status (OR 0.48 95% CI 0.34-0.70) in first admissions reduced odds of any readmission. Similar risk factors also influenced multiple readmissions with higher odds ratios. Conclusions Identification and adequate treatment of risk factors may reduce the chances of readmission.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Readmissão do Paciente , Adulto , Humanos , Estudos Retrospectivos , Estudos de Coortes , Pacientes Internados , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/terapia , Fatores de Risco
3.
J Addict Med ; 17(2): e101-e109, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36149004

RESUMO

INTRODUCTION: Treatment completion is associated with a better outcome in substance use disorders. We examined the rates of treatment completion and its predictors in patients admitted to specialized addiction treatment settings over a 13-year period. METHODS: Ours was a retrospective cohort study. We included consecutive 2850 patients admitted to the inpatient treatment between January 2007 and December 2019. We divided the patients into 2 groups: completed versus premature discontinuation of treatment. The predictor variables were based on previous research, clinical experience, and availability of the digital record. RESULTS: The number of patients who completed and discontinued treatments was 1873 (72.6%) and 707 (27.4%), respectively. The inpatient treatment discontinuation rate varied widely during the study period (18% in 2007 and 41% in 2012). The average rate of treatment discontinuation was 27%. The change-point analysis showed 5 statistically significant change points in the years 2008, 2010, 2012, 2014, and 2016. Patients who were prescribed medications for alcohol and opioid dependence and those who were on opioid agonist treatment had 4.7 and 6.3 higher odds of completing inpatient treatment than those who were not on medication. Patients with physical and psychiatric comorbidities had higher odds of treatment completion. Patients with a primary diagnosis of opioid dependence had lower odds of treatment completion than those with alcohol dependence. CONCLUSIONS: The rates of discontinuation may vary with concurrent changes in the treatment policies. Awareness of the risk factors and policy measures that may improve treatment completion must aid in informed decision making.


Assuntos
Alcoolismo , Transtornos Relacionados ao Uso de Opioides , Humanos , Estudos Retrospectivos , Pacientes Internados , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Alcoolismo/epidemiologia , Alcoolismo/terapia , Fatores de Risco
4.
Subst Use Misuse ; 57(1): 123-133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34668819

RESUMO

BACKGROUND: Alcohol use disorder (AUD) is a relapsing-remitting disease that accounted for a sizable proportion of all-cause adult inpatient stays. OBJECTIVES: To determine the predictors of any and multiple readmissions to inpatient care for AUD within 5 years of the index admission. METHODS: This retrospective, register-based cohort study assessed consecutive patients with AUD admitted to a publicly-funded inpatient service between January 2007 and December 2014. Binary logistic regression was used to determine independent predictors for readmissions based on relevant demographic, clinical, and treatment variables that showed significant differences (p < 0.05) on univariate analysis. RESULTS: Among 938 patients (age 35.9 ± 10.3 years; duration of alcohol use 159.6 ± 104.5 months; dual diagnosis 19%; comorbidity of substance use disorder 49.3%; medical disorder 34.8%, 299 (31.9%) and 115 (12.3%) had any and multiple readmissions, respectively. Comorbid "severe mental illness" (Odds ratio [OR] 1.99, 95% confidence interval [CI] 1.11-3.57) and urban residence (OR 1.58, 95% CI 1.13-2.18) increased the odds of any readmission; "Improved" status at discharge (OR 0.51, 95% CI 0.35-0.72) during index hospitalization reduced odds of readmission. Additionally, any medical or psychiatric comorbidities increased (OR 2.23, 95% CI 1.26-3.97), and comorbid substance use disorder decreased (OR 0.41, 95% CI 0.19-0.89) risk of multiple readmissions. CONCLUSIONS: Clinicians could identify patients at-risk for any and multiple readmissions during the index hospitalization. A policy aimed at reducing the risk of rehospitalization, healthcare cost, and stigma should pay attention to the predictors of readmission. Such policy should further benefit resource-limited settings.


Assuntos
Alcoolismo , Adulto , Alcoolismo/epidemiologia , Alcoolismo/terapia , Estudos de Coortes , Humanos , Pacientes Internados , Pessoa de Meia-Idade , Readmissão do Paciente , Estudos Retrospectivos , Fatores de Risco
5.
Nanoscale ; 13(43): 18096-18102, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34730591

RESUMO

Carbon nanotubes (CNTs) have long been heralded as the material of choice for next-generation membranes. Some studies have suggested that boron nitride nanotubes (BNNTs) may offer higher transport of pure water than CNTs, while others conclude otherwise. In this work, we use a combination of simulations and experimental data to uncover the causes of this discrepancy and investigate the flow resistance through BNNT membranes in detail. By dividing the resistance of the nanotube membranes into their contributing components, we study the effects of pore end configuration, membrane length, and BNNT atom partial charges. Most molecular simulation studies of BNNT membranes use short membranes connected to high and low pressure reservoirs. Here we find that flow resistances in these short membranes are dominated by the resistance at the pore ends, which can obscure the understanding of water transport performance through the nanotubes and comparison between different nanotube materials. In contrast, it is the flow resistance inside the nanotubes that dominates microscale-thick laboratory membranes, and end resistances tend to be negligible. Judged by the nanotube flow resistance alone, we therefore find that CNTs are likely to consistently outperform BNNTs. Furthermore, we find a large role played by the choice of partial charges on the BN atoms in the flow resistance measurements in our molecular simulations. This paper highlights a way forward for comparing molecular simulations and experimental results.

6.
Br J Dermatol ; 183(6): 1037-1048, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32286683

RESUMO

BACKGROUND: Brodalumab is efficacious for the treatment of moderate-to-severe plaque psoriasis through 52 weeks. OBJECTIVES: To evaluate the efficacy and safety of brodalumab through 120 weeks, including following withdrawal and retreatment. METHODS: At baseline, patients were randomized to brodalumab (n = 222) or placebo (n = 220). At week 12, patients achieving a static Physician's Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1) with brodalumab were rerandomized to brodalumab (n = 83) or placebo (n = 84; later re-treated with brodalumab if sPGA ≥ 3 occurred), and patients receiving placebo switched to brodalumab (n = 208). Safety was assessed by exposure-adjusted rates of treatment-emergent adverse events. RESULTS: Among those who achieved sPGA 0/1 at week 12 and were rerandomized to brodalumab, 96% and 80% using observed data, respectively, and 74% and 61% using nonresponder imputation, respectively, achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) and PASI 100 at week 120. Following withdrawal from brodalumab, return of disease occurred after a mean ± SD duration of 74·7 ± 50·5 days. Among those who switched from brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55% and 51% at week 20, respectively and 94% and 75% at week 120, respectively; PASI 100 rates at week 120 were 75% and 60%, respectively. Efficacy was maintained through week 120 in those receiving brodalumab after placebo. No new safety signals were observed. CONCLUSIONS: These findings indicate that brodalumab is efficacious and safe for continuous long-term treatment of psoriasis, and support the potential for response after discontinuation and retreatment.


Assuntos
Anticorpos Monoclonais , Psoríase , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Humanos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
7.
Br J Dermatol ; 180(2): 306-314, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30328108

RESUMO

BACKGROUND: Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has demonstrated superior efficacy and safety over ustekinumab as induction therapy for moderate-to-severe psoriasis. OBJECTIVES: To evaluate the efficacy and safety of brodalumab through week 52 in patients who had inadequate responses to ustekinumab. METHODS: A subgroup analysis of the phase III AMAGINE-2/-3 double-blind randomized controlled trials was performed. Participants were aged 18-75 years and had a Psoriasis Area and Severity Index (PASI) ≥ 12, static Physician's Global Assessment score ≥ 3 and involvement of ≥ 10% body surface area. The studies were registered at ClinicalTrials.gov: AMAGINE-2, NCT01708603; AMAGINE-3, NCT01708629. RESULTS: At baseline, patients with or without prior biologic experience who had an adequate response at week 16 on ustekinumab or brodalumab had lower rates of involved body surface area, PASI, prior biologic use, psoriatic arthritis and body mass index than patients who experienced inadequate response at or after week 16. Among patients who experienced inadequate response to ustekinumab, those rescued with brodalumab had PASI ≥ 75%, ≥ 90% and 100% improvement response rates of 72·6%, 58·1% and 36·3%, respectively, at week 52 compared with 61·7%, 25·5% and 5·4%, respectively, in patients who continued ustekinumab. Exposure-adjusted rates of treatment-emergent adverse events were similar among patients rescued with brodalumab (377·3 adverse events per 100 patient-years) and those who remained on ustekinumab (389·9 adverse events per 100 patient-years). CONCLUSIONS: Among patients who experienced inadequate responses to ustekinumab, rescue with brodalumab improved skin clearance outcomes compared with continuing ustekinumab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Ustekinumab/uso terapêutico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/farmacologia , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Psoríase/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão/métodos , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento , Ustekinumab/farmacologia , Adulto Jovem
8.
J Eur Acad Dermatol Venereol ; 32(8): 1305-1313, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29512200

RESUMO

BACKGROUND: Patients with psoriasis have lesional symptoms, including itch, which can reduce quality of life. The efficacy and safety of brodalumab, an interleukin-17 receptor A antagonist, in treating moderate-to-severe psoriasis have been reported in three randomized, controlled, phase 3 trials (AMAGINE-1/-2/-3). OBJECTIVE: The effect of brodalumab on lesional symptoms was assessed using the psoriasis symptom inventory (PSI), a validated patient-reported instrument. METHODS: Patients were randomized to receive brodalumab (140 or 210 mg every 2 weeks [Q2W]), placebo (AMAGINE-1/-2/-3), or ustekinumab (AMAGINE-2/-3) during a 12-week induction phase, followed by a maintenance phase through week 52. Patients electronically rated the severity of PSI items (itch, burning, stinging, pain, redness, scaling, cracking and flaking) during the previous 24 h on a scale of 0 (not at all severe) to 4 (very severe). At each visit, the PSI total score responder status was assessed, with responders defined as having an average weekly total inventory score ≤8 with no item score >1 at week 12. RESULTS: Across AMAGINE-1/-2/-3, brodalumab was associated with improvements in PSI total scores and itch scores vs. placebo from week 2 through week 12 (P < 0.001 in both domains). In AMAGINE-2/-3, brodalumab 210 mg Q2W demonstrated faster onset of PSI total score and itch responses (week 2, 22.1% and 36.4%, respectively) vs. ustekinumab (week 2, 6.9% and 17.1%, respectively) and was associated with improved itch responses vs. ustekinumab after 52 weeks of constant treatment. CONCLUSION: Brodalumab demonstrated rapid, robust improvements in symptoms assessed by the PSI, including itch, vs. placebo and ustekinumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Prurido/tratamento farmacológico , Psoríase/tratamento farmacológico , Ustekinumab/uso terapêutico , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Eritema/tratamento farmacológico , Eritema/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Dor/etiologia , Medidas de Resultados Relatados pelo Paciente , Prurido/etiologia , Psoríase/complicações , Índice de Gravidade de Doença , Avaliação de Sintomas
9.
Br J Dermatol ; 179(2): 320-328, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29488226

RESUMO

BACKGROUND: Biologics are being used increasingly to treat moderate-to-severe psoriasis. Efficacy may differ in patients with previous exposure to biologics. OBJECTIVES: To investigate the impact of previous biologic exposure on the efficacy and safety of brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS: Two placebo- and ustekinumab-controlled phase III clinical trials. There was an initial 12-week induction phase where patients were treated with brodalumab [210 mg or 140 mg every 2 weeks (Q2W)], ustekinumab or placebo. Efficacy end points included ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment (score of 0 or 1) vs. placebo, PASI 100 vs. ustekinumab, Dermatology Life Quality Index and Psoriasis Symptom Inventory. Adverse events were monitored throughout. RESULTS: In total, 493 patients [334 (27%) brodalumab 210 mg Q2W and 159 (26%) ustekinumab] had received prior biologics; 150 (12%) and 62 (10%), respectively, reported previously failed treatment with a biologic. Brodalumab efficacy in patients with or without previous exposure to biologics was statistically equivalent: 40·9% and 39·5% of biologic-naive and -experienced patients achieved PASI 100 at week 12, compared with 21·1% and 17·0% with ustekinumab (both P < 0·001). In patients where prior biologics had been successful or failed, 41·7% and 32·0% achieved PASI 100, compared with 21·1% and 11·3% with ustekinumab. Tolerability was similar, and did not appear to be influenced by previous treatment with biologics. CONCLUSIONS: The efficacy of brodalumab 210 mg Q2W was similar regardless of prior biological therapy (P = 0·31, 0·32 and 0·64 for PASI 75, 90 and 100, respectively). Almost twice as many patients achieved PASI 100 or complete clearance with brodalumab at week 12 compared with ustekinumab; the differences were most noticeable where previous biologics had failed. Both treatments were well tolerated.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Produtos Biológicos/administração & dosagem , Substituição de Medicamentos , Psoríase/tratamento farmacológico , Ustekinumab/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Produtos Biológicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/efeitos adversos
10.
Compr Psychiatry ; 72: 25-33, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27705838

RESUMO

BACKGROUND: Post-partum depression (PPD) is the common adverse outcome of child bearing which affects the wellbeing of both mother and newborn and has long-term effects. Hence, reliable potential biological tests for early detection of PPD are essential. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were associated with depressive disorders and the present study estimated the levels of serum FSH, LH in postpartum depression and explored them as predictive biomarkers in the development of PPD. METHODS: In this nested case control study done at a tertiary care hospital in South India, 450 postpartum women were screened at 6th week post-delivery for PPD. Socio-demographic and clinical data were recorded and depressive symptoms were assessed using Edinburgh Postnatal Depression Scale (EPDS). Out of 450 subjects screened, 100 women with depressive symptoms were categorized as cases and 100 controls were selected from the remaining subjects matching for age and BMI with cases. Serum levels of FSH and LH were measured using direct competitive immunoassay by chemiluminescene technology. RESULTS: Serum LH/FSH ratio was found to be significantly (p=0.02) low in PPD women when compared to normal postpartum subjects. We also found a significant negative correlation between LH/FSH ratio and EPDS scores. Based on the receiver operating characteristic curve, the optimal cut-off value for serum of LH/FSH levels in predicting postpartum depression was estimated to be 0.22mlU/mL with an AUC of 0.598 (95%CI, 0.291-0.859). CONCLUSION: Our study demonstrated that low LH/FSH ratio after delivery was associated with increased risk for the development of PPD. Low LH/FSH ratio at six-week post delivery can be used as a robust biochemical predictor of post-partum depression.


Assuntos
Depressão Pós-Parto/sangue , Depressão Pós-Parto/diagnóstico , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Depressão Pós-Parto/psicologia , Feminino , Humanos , Índia/epidemiologia , Recém-Nascido , Mães/psicologia , Período Pós-Parto/sangue , Período Pós-Parto/psicologia , Valor Preditivo dos Testes , Adulto Jovem
11.
Ann Oncol ; 27(2): 339-44, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26578722

RESUMO

BACKGROUND: Carboplatin (C) and paclitaxel (P) are standard treatments for carcinoma of unknown primary (CUP). Everolimus, an mTOR inhibitor, exhibits activity in diverse cancer types. We did a phase II trial combining everolimus with CP for CUP. We also evaluated whether a gene expression profiling (GEP) test that predicts tissue of origin (TOO) could identify responsive patients. PATIENTS AND METHODS: A tumor biopsy was required for central confirmation of CUP and GEP. Patients with metastatic, untreated CUP received everolimus (30 mg weekly) with P (200 mg/m(2)) and C (area under the curve 6) every 3 weeks. The primary end point was response rate (RR), with 22% needed for success. The GEP test categorized patients into two groups: those having a TOO where CP is versus is not considered standard therapy. RESULTS: Of 45 assessable patients, the RR was 36% (95% confidence interval 22% to 51%), which met criteria for success. Grade ≥3 toxicities were predominantly hematologic (80%). Adequate tissue for GEP was available in 38 patients and predicted 10 different TOOs. Patients with a TOO where platinum/taxane is a standard (n = 19) tended to have higher RR (53% versus 26%) and significantly longer PFS (6.4 versus 3.5 months) and OS (17.8 versus 8.3 months, P = 0.005), compared with patients (n = 19) with a TOO where platinum/taxane is not standard. CONCLUSIONS: Everolimus combined with CP demonstrated promising antitumor activity and an acceptable side-effect profile. A tumor biomarker identifying TOO may be useful to select CUP patients for specific antitumor regimens. CLINICALTRIALSGOV: NCT00936702.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Everolimo/uso terapêutico , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Neoplasias Primárias Desconhecidas/genética , Paclitaxel/uso terapêutico , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/patologia , Estudos Prospectivos , Resultado do Tratamento
12.
Eur J Neurol ; 23(3): 548-53, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26518615

RESUMO

BACKGROUND: Successful return to work after stroke may improve economic circumstances, quality of life and overall life satisfaction, but not all stroke survivors are able to return to work. AIM: Our aim was to determine what proportion of previously employed patients return to work after an acute stroke resulting in mild to moderate disability and to examine factors associated with a successful return to work. METHODS: Patients 18-60 years of age who were previously employed and who had a first-ever stroke 3 months to 2 years previously resulting in mild to moderate disability (modified Rankin score ≤3) were recruited. Socio-demographic and clinical information was collected and anxiety, depression and social support were assessed using previously validated instruments. Multivariate logistic regression was used to assess factors associated with a successful return to work. RESULTS: Of 141 patients (mean age ± SD 48 ± 8.8 years), 74 (52.5%) returned to work after stroke. Multivariate analysis demonstrated that a lower modified Rankin scale at 3 months [odds ratio (OR) 3.70, 95% confidence interval (CI) 1.77-7.76], younger age (OR 2.24, 95% CI 1.07-4.67) and a professional or business job (OR 3.02, 95% CI 1.44-6.34) were significantly associated with successful return to work and revealed that anxiety, depression and social support score did not affect patients' decision to return to work (P = 0.17, 0.61 and 0.27, respectively). CONCLUSIONS: Amongst patients with mild to moderate disability after stroke, almost half do not return to work, and this is determined by functional disability and type of job rather than psychosocial factors such as anxiety and depression.


Assuntos
Pessoas com Deficiência/estatística & dados numéricos , Retorno ao Trabalho/estatística & dados numéricos , Acidente Vascular Cerebral/epidemiologia , Adulto , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
13.
Artigo em Inglês | MEDLINE | ID: mdl-26274270

RESUMO

The deformation and breakup of an axisymmetric, conducting drop suspended in a nonconducting medium and subjected to an external electric field is numerically investigated here using an electrokinetic model. This model uses a combined level set-volume of fluid formulation of the deformable surfaces, along with a multiphase implementation of the Nernst-Planck equation for transport of ions, that allows for varying conductivity inside the drop. A phase diagram, based on a parametric study, is used to characterize the stability conditions. Stable drops with lower ion concentration are characterized by longer drop shapes than those achieved at higher ion concentrations. For higher drop ion concentration, greater charge accumulation is observed at drop tips. Consequently, such drops break up by pinching off rather than tip streaming. The charge contained in droplets released from unstable drops is shown to increase with drop ion concentration. These dynamic drop behaviors depend on the strength of the electric field and the concentration of ions in the drop and result from the interplay between the electric forces arising from the permittivity jump at the drop interface and the ions in the bulk.

14.
J Pharm Sci ; 104(7): 2177-82, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25940933

RESUMO

Transungual drug delivery of antifungals is considered highly desirable to treat common nail disorders such as onychomycosis, due to localized effects, and improved adherence resulting from minimal systemic adverse events. However, the development of effective topical therapies has been hampered by poor nail penetration. An effective topical antifungal must permeate through, and under the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. We present here the formulation development program to provide effective transungual and subungual delivery of efinaconazole, the first topical broad spectrum triazole specifically developed for onychomycosis treatment. We discuss the important aspects encompassing the formulation development program for efinaconazole topical solution, 10%, focusing on its solubility in a number of solvents, in vitro penetration through the nail, and in vivo efficacy. Efinaconazole topical solution, 10% is a stable, non-lacquer, antifungal with a unique combination of ingredients added to an alcohol-based formulation to provide low surface tension and good wetting properties. This low surface tension is believed to affect effective transungual delivery of efinaconazole and believed to provide a dual mode of delivery by accessing the nail bed by wicking into the space between the nail and nail plate.


Assuntos
Dermatoses do Pé/tratamento farmacológico , Unhas/efeitos dos fármacos , Onicomicose/tratamento farmacológico , Soluções Farmacêuticas/administração & dosagem , Soluções Farmacêuticas/química , Triazóis/administração & dosagem , Triazóis/química , Administração Tópica , Antifúngicos/administração & dosagem , Antifúngicos/química , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Doenças da Unha/tratamento farmacológico , Permeabilidade , Solubilidade
15.
Int J Biol Macromol ; 72: 199-209, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25109458

RESUMO

Pectin-based biocomposite hydrogels were produced by internal gelation, using different hydroxyapatite (HA) powders from commercial source or synthesized by the wet chemical method. HA possesses the double functionality of cross-linking agent and inorganic reinforcement. The mineralogical composition, grain size, specific surface area and microstructure of the hydroxyapatite powders are shown to strongly influence the properties of the biocomposites. Specifically, the grain size and specific surface area of the HA powders are strictly correlated to the gelling time and rheological properties of the hydrogels at room temperature. Pectin pH is also significant for the formation of ionic cross-links and therefore for the hydrogels stability at higher temperatures. The obtained results point out that micrometric-size hydroxyapatite can be proposed for applications which require rapid gelling kinetics and improved mechanical properties; conversely the nanometric hydroxyapatite synthesized in the present work seems the best choice to obtain homogeneous hydrogels with more easily controlled gelling kinetics.


Assuntos
Durapatita/química , Hidrogéis/química , Nanocompostos/química , Pectinas/química , Temperatura Alta , Cinética , Pós/química , Reologia , Propriedades de Superfície , Temperatura , Difração de Raios X
16.
Reprod Toxicol ; 52: 18-25, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25527861

RESUMO

Efinaconazole is a new triazole antifungal for topical treatment of onychomycosis. The reproductive and developmental toxicity of efinaconazole was characterized in fertility and early embryonic development (rat), embryo-fetal development (rat and rabbit), and peri/post-natal development (rat) studies in accordance with current ICH guidances. In the fertility study, maternal reproductive toxicity was noted as estrous cycle prolongation (NOAEL=5mg/kg/day) but there were no male reproductive effects even in the presence of paternal toxicity (NOAEL=25mg/kg/day). Rat embryo-fetal and perinatal pup lethality was the most sensitive (NOAEL=5mg/kg/day) efinaconazole developmental toxicity and was noted at maternally toxic doses. Efinaconazole did not affect rabbit embryo-fetal development at maternally toxic doses (NOAEL=10mg/kg/day). No malformations were induced by efinaconazole in rats or rabbits. When compared with systemic exposures observed in onychomycosis patients, embryo-fetal toxicity in rats was noted at high (>100-fold) multiples of systemic exposure.


Assuntos
Antifúngicos/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Triazóis/toxicidade , Animais , Animais Recém-Nascidos , Relação Dose-Resposta a Droga , Ciclo Estral/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Morte Fetal , Masculino , Coelhos , Ratos , Triazóis/administração & dosagem
17.
Ann R Coll Surg Engl ; 96(6): 475-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25198982

RESUMO

INTRODUCTION: Discussing and planning the appropriate management for suspicious renal masses can be challenging. With the development of nephrometry scoring methods, we aimed to evaluate the ability of the RENAL nephrometry score to predict both the incidence of postoperative complications and the change in renal function after a partial nephrectomy. METHODS: This was a retrospective study including 128 consecutive patients who underwent a partial nephrectomy (open and laparoscopic) for renal lesions in a tertiary UK referral centre. Univariate and multivariate ordinal regression models were used to identify associations between Clavien-Dindo classification and explanatory variables. The Kendall rank correlation coefficient was used to examine an association between RENAL nephrometry score and a drop in estimated glomerular filtration rate (eGFR) following surgery. RESULTS: An increase in the RENAL nephrometry score of one point resulted in greater odds of being in a higher Clavien-Dindo classification after controlling for RENAL suffix and type of surgical procedure (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.04-1.64, p=0.043). Furthermore, a patient with the RENAL suffix 'p' (ie posterior location of tumour) had increased odds of developing more serious complications (OR: 2.60, 95% CI: 1.07-6.30, p=0.042). A correlation was shown between RENAL nephrometry score and postoperative drop in eGFR (Kendall's tau coefficient -0.24, p=0.004). CONCLUSIONS: To our knowledge, this is the first study that has shown the predictive ability of the RENAL nephrometry scoring system in a UK cohort both in terms of postoperative complications and change in renal function.


Assuntos
Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Renais/patologia , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Tratamentos com Preservação do Órgão/efeitos adversos , Tratamentos com Preservação do Órgão/métodos , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco/métodos , Índice de Gravidade de Doença , Adulto Jovem
18.
Virus Genes ; 48(1): 89-95, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24174279

RESUMO

A total of 85 samples (58.0 %) were found to be positive for Canine parvovirus (CPV) by PCR assay (Hfor/Hrev primers) out of 158 suspected faecal samples of dogs collected from various states/union territories of India. Nine CPV isolates could be obtained in A-72 cell line. The sequencing of the partial VP2 gene of CPV identified the predominant CPV strain as CPV-2a (Ser297Ala) with one CPV-2b (Ser297Ala) and another CPV-2a variant strain (Ser297Gly). Several non-synonymous and synonymous mutations were also recorded in this study. The phylogenetic tree revealed that most of the CPV sequences from Tamil Nadu (Southern India) and Maharashtra (Western India) obtained during 2011 and few sequences from Northern India obtained during 2012 were grouped together along with CPV-2a (Ser297Ala) strains from China and India and followed the same evolution; although there was definitive indication of separate lineages too by few other sequences.


Assuntos
Fezes/virologia , Variação Genética , Parvovirus Canino/genética , Parvovirus Canino/isolamento & purificação , Filogenia , Proteínas Estruturais Virais/genética , Animais , Análise por Conglomerados , DNA Viral/genética , Cães , Índia , Dados de Sequência Molecular , Mutação Puntual , Análise de Sequência de DNA , Homologia de Sequência
19.
20.
BJOG ; 120(8): 932-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23530609

RESUMO

OBJECTIVE: To assess the prevalence of overweight and obesity, and the impact of body mass index (BMI) on maternal and neonatal outcomes, in a UK obstetric population. DESIGN: Retrospective study. SETTING: A tertiary referral unit in Northern Ireland. POPULATION: A total of 30 298 singleton pregnancies over an 8-year period, 2004-2011. METHODS: Women were categorised according to World Health Organization classification: underweight (BMI < 18.50 kg/m(2)); normal weight (BMI 18.50-24.99 kg/m(2); reference group); overweight (BMI 25.00-29.99 kg/m(2)); obese class I (BMI 30.00-34.99 kg/m(2)); obese class II (BMI 35-39.99 kg/m(2)); and obese class III (BMI ≥ 40 kg/m(2)). Maternal and neonatal outcomes were examined using logistic regression, adjusted for confounding variables. MAIN OUTCOME MEASURES: Maternal and neonatal outcomes. RESULTS: Compared with women of normal weight, women who were overweight or obese class I were at significantly increased risk of hypertensive disorders of pregnancy (OR 1.9, 99% CI 1.7-2.3; OR 3.5, 99% CI 2.9-4.2); gestational diabetes mellitus (OR 1.7, 99% CI 1.3-2.3; OR 3.7, 99% CI 2.8-5.0); induction of labour (OR 1.2, 99% CI 1.1-1.3; OR 1.3, 99% CI 1.2-1.5); caesarean section (OR 1.4, 99% CI 1.3-1.5; OR 1.8, 99% CI 1.6-2.0); postpartum haemorrhage (OR 1.4, 99% CI 1.3-1.5; OR 1.8, 1.6-2.0); and macrosomia (OR 1.5, 99% CI 1.3-1.6; OR 1.9, 99% CI 1.6-2.2), with the risks increasing for obese classes II and III. Women in obese class III were at increased risk of preterm delivery (OR 1.6, 99% CI 1.1-2.5), stillbirth (OR 3.0, 99% CI 1.0-9.3), postnatal stay > 5 days (OR 2.1, 99% CI 1.5-3.1), and infant requiring admission to a neonatal unit (OR 1.6, 99% CI 1.0-2.6). CONCLUSIONS: By categorising women into overweight and obesity subclassifications (classes I -III), this study clearly demonstrates an increasing risk of adverse outcomes across BMI categories, with women who are overweight also at significant risk.


Assuntos
Obesidade/complicações , Sobrepeso/complicações , Adulto , Índice de Massa Corporal , Peso Corporal , Feminino , Humanos , Recém-Nascido , Irlanda do Norte , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Gravidez , Resultado da Gravidez , Prevalência , Estudos Retrospectivos , Fatores de Risco
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