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1.
Medicine (Baltimore) ; 98(45): e17170, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702607

RESUMO

Reversible cerebral vasoconstriction syndrome (RCVS) is a rare clinical syndrome accompanying with severe headache as its main symptom. Postpartum reversible cerebral vasoconstriction syndrome (PPRCVS) refers to RCVS occurring in the puerperium, in which it has a low incidence, and that is easily missed diagnosed and misdiagnosed in clinical practice.By searching in CNKI and Wanfang databases, 9 published articles reported PPRCVS were found, totally including 12 cases with PPRCVS. The clinical data of these 12 cases were accordingly analyzed and summarized. The characteristics of these cases were compared with those reported in other countries, and eventually the clinical characteristics of Chinese PPRCVS patients were summarized.The clinical characteristics of Chinese PPRCVS patients were basically as same as those found in other countries, while the onset age was earlier, PPRCVS often occurred earlier after delivery, with higher proportions of concomitant symptoms and abnormal laboratory and imaging examinations; moreover, and fewer patients were diagnosed by digital subtraction angiography (DSA).


Assuntos
Angiografia Digital/métodos , Quimioterapia Combinada/métodos , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/tratamento farmacológico , Adulto , Idade de Início , China/epidemiologia , Feminino , Humanos , Incidência , Imagem por Ressonância Magnética , Período Pós-Parto , Vasoespasmo Intracraniano/epidemiologia
2.
BMJ ; 366: l5016, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511230

RESUMO

OBJECTIVE: To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN: Blinded randomized placebo controlled trial. SETTING: Linqu County, Shandong province, China. PARTICIPANTS: 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. INTERVENTIONS: H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). MAIN OUTCOME MEASURES: Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. RESULTS: 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. CONCLUSIONS: H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339768.


Assuntos
Infecções por Helicobacter/terapia , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiulcerosos/administração & dosagem , Biópsia , China/epidemiologia , Suplementos Nutricionais , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Alho/química , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastroscopia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Inibidores da Bomba de Prótons/administração & dosagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/prevenção & controle , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vitaminas/administração & dosagem
3.
J Drugs Dermatol ; 18(9): 924-927, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524349

RESUMO

Acne is primarily an inflammatory disease. Anti-inflammatory dose doxycycline (40mg: 30mg immediate release and 10mg delayed release beads) is approved for the treatment of rosacea but with demonstrated efficacy for acne. Fixed combination adapalene 0.3% and benzoyl peroxide 2.5% gel is a once-daily formulation approved for the topical management of acne vulgaris. It has both anti-inflammatory and anti-comedogenic properties. Options for management of severe acne are somewhat limited; many patients are not candidates for or refuse treatment with isotretinoin. Systemic antibiotics may be indicated; acne treatment guidelines emphasize antibiotic stewardship in light of increasing concerns about antibiotic resistance and call for the judicious use of conventional systemic antibiotics. This single-center, open label pilot study involving 20 subjects with severe acne assessed the effects of combination treatment using anti-inflammatory dose doxycycline plus adapalene 0.3% and benzoyl peroxide 2.5% gel on IGA scores as well as inflammatory lesion, non-inflammatory lesion, and nodule counts. By week 12, 95% of subjects had at least a 2-grade improvement in IGA scores. Reductions in inflammatory and non-inflammatory lesion counts were statistically significant beginning at week 4 and continuing through week 12. By week 4, the percentage of patients with 0 nodules was 70%, compared to baseline of 20%. Further improvements were seen through week 12. Treatment was well-tolerated with no serious treatment-related adverse events. Combination treatment with anti-inflammatory dose doxycycline plus combination adapalene 0.3% and benzoyl peroxide 2.5% gel is safe and effective for management of severe acne. J Drugs Dermatol. 2019;18(9):924-927.


Assuntos
Acne Vulgar/tratamento farmacológico , Combinação Adapaleno e Peróxido de Benzoil/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Doxiciclina/administração & dosagem , Combinação Adapaleno e Peróxido de Benzoil/efeitos adversos , Administração Cutânea , Administração Oral , Adolescente , Adulto , Criança , Fármacos Dermatológicos/efeitos adversos , Relação Dose-Resposta a Droga , Doxiciclina/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Géis , Humanos , Masculino , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
4.
Magy Onkol ; 63(3): 202-207, 2019 Sep 18.
Artigo em Húngaro | MEDLINE | ID: mdl-31533140

RESUMO

In recent years widespread use of immuno-oncology drugs are in the focus of modern systemic anticancer therapies. Parallel to the evolving role of immune checkpoint inhibitors many people believe that using chemotherapy is coming to an end. Moreover laymen opinions are being communicated about the detrimental role of chemotherapy. The aim of this article is to dissolve this misbelief. The manuscript details the immunomodulatory effects of chemotherapy. Having the ability to stop division of cancer cells and kill them together with immunomodulatory effects, chemotherapy is an ideal partner for combination with immune checkpoint inhibitors. There is increasing number of evidence for synergistic effect between chemotherapy and immuno-oncology drugs. Ongoing and future clinical trials will determine the optimal combinations.


Assuntos
Antineoplásicos/uso terapêutico , Sistema Imunitário/efeitos dos fármacos , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Antineoplásicos/efeitos adversos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/patologia , Neoplasias/imunologia
5.
Cochrane Database Syst Rev ; 9: CD002009, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483853

RESUMO

BACKGROUND: People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often. This is an update of a previously published review. OBJECTIVES: To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis. SEARCH METHODS: We searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.Date of the most recent search: 31 January 2019.We also searched online trial registries. Date of latest search: 25 February 2019. SELECTION CRITERIA: All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The two authors independently selected the studies to be included in the review and assessed the risk of bias of each study; authors also assessed the quality of the evidence using the GRADE criteria. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies. MAIN RESULTS: We identified 15 studies for possible inclusion in the review. Five studies reporting results from a total of 354 participants (aged 5 to 50 years) were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One cross-over trial had 26 participants who received the first-arm treatment but only 15 received the second arm. One study had a low risk of bias for all criteria assessed; the remaining included studies had a high risk of bias from blinding, but for other criteria were judged to have either an unclear or a low risk of bias.There was little or no difference between treatment groups in: forced expiratory volume in one second, mean difference (MD) 0.33 (95% confidence interval (CI) -2.81 to 3.48, moderate-quality evidence); forced vital capacity, MD 0.29 (95% CI -6.58 to 7.16, low-quality evidence); % weight for height, MD -0.82 (95% CI -3.77 to 2.13, low-quality evidence); body mass index, MD 0.00 (95% CI -0.42 to 0.42, low-quality evidence); or in the incidence of ototoxicity, relative risk 0.56 (95% CI 0.04 to 7.96, moderate-quality evidence). Once-daily treatment in children probably improved the percentage change in creatinine, MD -8.20 (95% CI -15.32 to -1.08, moderate-quality evidence), but showed no difference in adults, MD 3.25 (95% CI -1.82 to 8.33, moderate-quality evidence). The included trials did not report antibiotic resistance patterns or quality of life. AUTHORS' CONCLUSIONS: Once- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis. There is evidence of less nephrotoxicity in children.


Assuntos
Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Fibrose Cística/tratamento farmacológico , Pneumopatias , Aminoglicosídeos/administração & dosagem , Antibacterianos/administração & dosagem , Fibrose Cística/complicações , Esquema de Medicação , Quimioterapia Combinada/métodos , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Injeções Intravenosas , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Ensaios Clínicos Controlados Aleatórios como Assunto , Capacidade Vital/efeitos dos fármacos
6.
BMJ ; 366: l5125, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562117

RESUMO

OBJECTIVE: To investigate whether fenofibrate as add-on to statin treatment reduce persistent cardiovascular risk in adults with metabolic syndrome in a real world setting. DESIGN: Propensity matched cohort study. SETTING: Population based cohort in Korea. PARTICIPANTS: 29 771 adults with metabolic syndrome (≥40 years) receiving statin treatment. 2156 participants receiving combined treatment (statin plus fenofibrate) were weighted based on propensity score in a 1:5 ratio with 8549 participants using statin only treatment. MAIN OUTCOME MEASURE: Primary outcome was composite cardiovascular events including incident coronary heart disease, ischaemic stroke, and death from cardiovascular causes. RESULTS: The incidence rate per 1000 person years of composite cardiovascular events was 17.7 (95% confidence interval 14.4 to 21.8) in the combined treatment group and 22.0 (20.1 to 24.1) in the statin group. The risk of composite cardiovascular events was significantly reduced in the combined treatment group compared with statin group (adjusted hazard ratio 0.74, 95% confidence interval 0.58 to 0.93; P=0.01). The significance was maintained in the on-treatment analysis (hazard ratio 0.63, 95% confidence interval 0.44 to 0.92; P=0.02). The risk of incident coronary heart disease, ischaemic stroke, and cardiovascular death was lower in the combined treatment group than statin group but was not significant. Participant characteristics did not appear to be associated with the low risk of composite cardiovascular events with combined treatment. CONCLUSION: In this propensity weighted cohort study of adults with metabolic syndrome, the risk of major cardiovascular events was significantly lower with fenofibrate as add-on to statin treatment than with statin treatment alone.


Assuntos
Doenças Cardiovasculares , Fenofibrato/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Adulto , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Causas de Morte , Estudos de Coortes , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Avaliação de Resultados (Cuidados de Saúde) , Pontuação de Propensão , República da Coreia/epidemiologia , Fatores de Risco
7.
Cochrane Database Syst Rev ; 8: CD009164, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31425618

RESUMO

BACKGROUND: Pharmacological treatments for tobacco dependence, such as nicotine replacement therapy (NRT), have been shown to be safe and effective interventions for smoking cessation. Higher levels of adherence to these medications increase the likelihood of sustained smoking cessation, but many smokers use them at a lower dose and for less time than is optimal. It is important to determine the effectiveness of interventions designed specifically to increase medication adherence. Such interventions may address motivation to use medication, such as influencing beliefs about the value of taking medications, or provide support to overcome problems with maintaining adherence. OBJECTIVES: To assess the effectiveness of interventions aiming to increase adherence to medications for smoking cessation on medication adherence and smoking abstinence compared with a control group typically receiving standard care. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register, and clinical trial registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform) to the 3 September 2018. We also conducted forward and backward citation searches. SELECTION CRITERIA: Randomised, cluster-randomised or quasi-randomised studies in which adults using active pharmacological treatment for smoking cessation were allocated to an intervention arm where there was a principal focus on increasing adherence to medications for tobacco dependence, or a control arm providing standard care. Dependent on setting, standard care may have comprised minimal support or varying degrees of behavioural support. Included studies used a measure that allowed assessment of the degree of medication adherence. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for eligibility, extracted data for included studies and assessed risk of bias. For continuous outcome measures, we calculated effect sizes as standardised mean differences (SMDs). For dichotomous outcome measures, we calculated effect sizes as risk ratios (RRs). In meta-analyses for adherence outcomes, we combined dichotomous and continuous data using the generic inverse variance method and reported pooled effect sizes as SMDs; for abstinence outcomes, we reported and pooled dichotomous outcomes. We obtained pooled effect sizes with 95% confidence intervals (CIs) using random-effects models. We conducted subgroup analyses to assess whether the primary focus of the adherence treatment ('practicalities' versus 'perceptions' versus both), the delivery approach (participant versus clinician-centred) or the medication type were associated with effectiveness. MAIN RESULTS: We identified two new studies, giving a total of 10 studies, involving 3655 participants. The medication adherence interventions studied were all provided in addition to standard behavioural support.They typically provided further information on the rationale for, and emphasised the importance of, adherence to medication or supported the development of strategies to overcome problems with maintaining adherence (or both). Seven studies targeted adherence to NRT, two to bupropion and one to varenicline. Most studies were judged to be at high or unclear risk of bias, with four of these studies judged at high risk of attrition or detection bias. Only one study was judged to be at low risk of bias.Meta-analysis of all 10 included studies (12 comparisons) provided moderate-certainty evidence that adherence interventions led to small improvements in adherence (i.e. the mean amount of medication consumed; SMD 0.10, 95% CI 0.03 to 0.18; I² = 6%; n = 3655), limited by risk of bias. Subgroup analyses for the primary outcome identified no significant subgroup effects, with effect sizes for subgroups imprecisely estimated. However, there was a very weak indication that interventions focused on the 'practicalities' of adhering to treatment (i.e. capabilities, resources, levels of support or skills) may be effective (SMD 0.21, 95% CI 0.03 to 0.38; I² = 39%; n = 1752), whereas interventions focused on treatment 'perceptions' (i.e. beliefs, cognitions, concerns and preferences; SMD 0.10, 95% CI -0.03 to 0.24; I² = 0%; n = 839) or on both (SMD 0.04, 95% CI -0.08 to 0.16; I² = 0%; n = 1064), may not be effective. Participant-centred interventions may be effective (SMD 0.12, 95% CI 0.02 to 0.23; I² = 20%; n = 2791), whereas those that are clinician-centred may not (SMD 0.09, 95% CI -0.05 to 0.23; I² = 0%; n = 864).Five studies assessed short-term smoking abstinence (five comparisons), while an overlapping set of five studies (seven comparisons) assessed long-term smoking abstinence of six months or more. Meta-analyses resulted in low-certainty evidence that adherence interventions may slightly increase short-term smoking cessation rates (RR 1.08, 95% CI 0.96 to 1.21; I² = 0%; n = 1795) and long-term smoking cessation rates (RR 1.16, 95% CI 0.96 to 1.40; I² = 48%; n = 3593). In both cases, the evidence was limited by risk of bias and imprecision, with CIs encompassing minimal harm as well as moderate benefit, and a high likelihood that further evidence will change the estimate of the effect. There was no evidence that interventions to increase adherence to medication led to any adverse events. Studies did not report on factors plausibly associated with increases in adherence, such as self-efficacy, understanding of and attitudes toward treatment, and motivation and intentions to quit. AUTHORS' CONCLUSIONS: In people who are stopping smoking and receiving behavioural support, there is moderate-certainty evidence that enhanced behavioural support focusing on adherence to smoking cessation medications can modestly improve adherence. There is only low-certainty evidence that this may slightly improve the likelihood of cessation in the shorter or longer-term. Interventions to increase adherence can aim to address the practicalities of taking medication, change perceptions about medication, such as reasons to take it or concerns about doing so, or both. However, there is currently insufficient evidence to confirm which approach is more effective. There is no evidence on whether such interventions are effective for people who are stopping smoking without standard behavioural support.


Assuntos
Adesão à Medicação/estatística & dados numéricos , Agonistas Nicotínicos/uso terapêutico , Abandono do Hábito de Fumar/métodos , Dispositivos para o Abandono do Uso de Tabaco , Tabagismo/tratamento farmacológico , Benzazepinas/uso terapêutico , Bupropiona/uso terapêutico , Quimioterapia Combinada/métodos , Humanos , Nortriptilina/uso terapêutico , Quinoxalinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Prevenção do Hábito de Fumar
8.
Cell Host Microbe ; 26(1): 35-47, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295423

RESUMO

Intensified treatment and control efforts since the early 2000s have dramatically reduced the burden of Plasmodium falciparum malaria. However, drug resistance threatens to derail this progress. In this review, we present four antimalarial resistance case studies that differ in timeline, technical approaches, mechanisms of action, and categories of resistance: chloroquine, sulfadoxine-pyrimethamine, artemisinin, and piperaquine. Lessons learned from prior losses of treatment efficacy, drug combinations, and control strategies will help advance mechanistic research into how P. falciparum parasites acquire resistance to current first-line artemisinin-based combination therapies. Understanding resistance in the clinic and laboratory is essential to prolong the effectiveness of current antimalarial drugs and to optimize the pipeline of future medicines.


Assuntos
Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Resistência a Medicamentos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Quimioterapia Combinada/métodos , Humanos
9.
Expert Opin Pharmacother ; 20(15): 1831-1836, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31322413

RESUMO

Introduction: Atypical meningiomas are aggressive tumors associated with high rates of recurrence and mortality. Current therapy is surgical resection followed by radiotherapy which has reasonable success rates. However, there are cases where surgical resection is not possible, and radiotherapy is not advisable. Areas covered: In this short review, the authors have searched the current literature for explorations of adjuvant treatments such as chemotherapy and pharmaceutical agents. Most current chemotherapeutic agents have been unsuccessful in producing radiographic reduction or disease stabilization, although drugs like somatostatin analogs and plant-derived chemotherapeutics have shown some promise. The authors note that most of the studies in this field have been case series with a few randomized trials present. This makes it hard to ascertain the effectiveness of the drugs and so further research is required in the field. Expert opinion: Finding pharmacotherapies to combat atypical meningiomas needs Big data genomic analysis. This will assist in generating drug candidates and a multidrug approach to therapy that will exploit several of the pathological pathways of atypical meningiomas. Using multidrug therapy that affects several pathways also addresses the issue of meningioma heterogeneity and adaptability.


Assuntos
Quimioterapia Combinada/métodos , Meningioma/tratamento farmacológico , Feminino , Humanos , Meningioma/patologia
10.
J Drugs Dermatol ; 18(7): 642-648, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31329402

RESUMO

Background: Pigmentation disorders are therapeutically challenging to treat, requiring complicated regimens. Objectives: Alternatives to hydroquinone (HQ) are desired. We evaluated the efficacy and tolerability of a non-HQ multi-action skin tone corrector (ETCS) developed to inhibit melanin production and improve skin quality. Design and Methods: Twice-daily use of ETCS and ETCS + AHA-Ret, a retinoid-based alpha hydroxy acid cream, was evaluated in subjects with mild to severe dyschromia. Digital images were obtained at baseline, 4, 8, and 12 weeks and included assessment of dyschromia, erythema, fine lines/wrinkles, pores, texture, and global improvement. Melanin Index (MI) measurements were obtained at baseline, 4, 8, and 12 weeks. Subject self-assessments were obtained over the course of the study. Adverse Events (AEs) were collected throughout the study. An extension study evaluated use over 16-weeks. Results: Significant mean reductions from baseline occurred in dyschromia for ETCS (n=42) and ETCS + AHA-Ret (n=10) over 12 weeks (P<0.0001, each). Significant mean reductions from baseline in MI were achieved in both groups at every timepoint (ETCS: P<0.0001; ETCS + AHA-Ret: P<0.02, 4 weeks; P<0.0001, 8 and 12 weeks). Substantial improvements were demonstrated in global improvement, fine lines/wrinkles, erythema, pores, and texture at 12 weeks. Reductions from baseline occurred in dyschromia and MI (P<0.0001, each) at 16 weeks. High levels of subject satisfaction were reported with nearly all subjects reporting reduced appearance of uneven skin tone/discoloration and lightened darker patches, and improvement in overall skin tone. Mild, transient AEs were reported with no discontinuations due to an AE. Conclusions: Twice daily use of ETCS led to early, significant reductions in dyschromia and melanin index. Combination use with a retinoid-based, AHA cream in the evening demonstrated enhanced reductions. ETCS effectively reduced hyperpigmentation, improved overall skin appearance, and was highly tolerable. J Drugs Dermatol. 2019;18(7):642-648.


Assuntos
Fármacos Dermatológicos/efeitos adversos , Hiperpigmentação/tratamento farmacológico , Melaninas/antagonistas & inibidores , Creme para a Pele/administração & dosagem , Preparações Clareadoras de Pele/administração & dosagem , Adulto , Idoso , Fármacos Dermatológicos/administração & dosagem , Combinação de Medicamentos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Melaninas/metabolismo , Pessoa de Meia-Idade , Retinoides/administração & dosagem , Retinoides/efeitos adversos , Envelhecimento da Pele/efeitos dos fármacos , Creme para a Pele/efeitos adversos , Creme para a Pele/química , Preparações Clareadoras de Pele/efeitos adversos , Preparações Clareadoras de Pele/química , Pigmentação da Pele/efeitos dos fármacos , Resultado do Tratamento
11.
Life Sci ; 232: 116622, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271767

RESUMO

AIMS: This study was designed to compare the effects of empagliflozin monotherapy and its combination with metformin on glucose and lipid modulations in T2DM mice. MAIN METHODS: Nine-week-old male C57BLKS/J db/db mice (n = 32) were used as T2DM model, and their age-matched C57BLKS/J db/m mice (n = 8) were used as normal control. A total of 32 db/db mice were randomly divided into four groups (n = 8/group): the DMT1 group, treated with metformin (250 mg/kg/day); the DMT2 group, treated with metformin (250 mg/kg/day) plus empagliflozin (10 mg/kg/day); the DMT3 group, treated with empagliflozin (10 mg/kg/day); the T2DM control group (DM), received 0.5% Natrosol. The db/m mice received same administration as DM group. KEY FINDINGS: After four-week treatments, compared with T2DM control (DM), the empagliflozin or its combination with metformin dramatically increased the levels of plasma HDL-C (139.6% and 154.9%, respectively), with significant decrease in plasma TC (22.9% and 13.7%, respectively) and plasma TG (26% and 19.7%, respectively) and in hepatic TG (30.3% and 28.6%, respectively). The protein expressions of SREBP1c (75.3% and 54.0%, respectively) and APOC-III (51.2% and 50.2%, respectively) were reduced, while CPT1A (304.0% and 221.4%, respectively) and ApoA1 levels (90.0% and 85.3%, respectively) were enhanced. Although both interventions improve above-mentioned lipid homeostasis, there were no statistic differences between two groups (p > 0.05). SIGNIFICANCE: Our study demonstrated that current dose of combination therapy may have no higher amelioration than empagliflozin monotherapy for glucose and lipid metabolism in male T2DM mice when it followed a treatment shorter than that expected during clinical treatment.


Assuntos
Compostos Benzidrílicos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/farmacologia , Animais , Compostos Benzidrílicos/metabolismo , Glicemia/efeitos dos fármacos , Modelos Animais de Doenças , Quimioterapia Combinada/métodos , Glucose/metabolismo , Glucosídeos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metformina/metabolismo , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Inibidores do Transportador 2 de Sódio-Glicose/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Resultado do Tratamento
12.
J Dermatol ; 46(9): 770-776, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270853

RESUMO

The efficacy of lauromacrogol injection therapy and intralesional triamcinolone for infantile hemangiomas (IH) has been well documented recently, but with an increase in serious or rare adverse reactions. The aim of this study is to investigate the safety concerns regarding intralesional injection of lauromacrogol combined with triamcinolone for IH and to study its effect on infant growth and development. A total of 1039 IH patients who were subjected to intralesional injection of lauromacrogol combined with triamcinolone in the Plastic Surgery Department of Shandong Provincial Hospital between 1 January 2015 and 31 May 2018 were enrolled in this study. When the dose of lauromacrogol and triamcinolone was less than 3.5 and 2.0 mg/kg respectively, no serious side-effects were observed. The adverse event rate reported was 7.7%. Among the 405 patients not subjected to propranolol before the last injection, the study included three modes of treatment response: regression (82.7%), stabilization (13.8%) and failure (3.5%). By comparing height and weight to the reference standards and also by comparisons between the same-sex groups, our results confirmed that there was no significant effect on children's height and weight, regardless of whether the injection therapy was combined with oral propranolol at the appropriate dose and with more than 4-week intervals. Intralesional injection of lauromacrogol combined with triamcinolone in the treatment of IH was highly safe and effective.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Hemangioma/tratamento farmacológico , Polidocanol/efeitos adversos , Soluções Esclerosantes/efeitos adversos , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Lactente , Injeções Intralesionais , Masculino , Polidocanol/administração & dosagem , Propranolol/administração & dosagem , Propranolol/efeitos adversos , Estudos Retrospectivos , Soluções Esclerosantes/administração & dosagem , Resultado do Tratamento , Triancinolona/administração & dosagem , Triancinolona/efeitos adversos
13.
Ann R Coll Surg Engl ; 101(7): 514-518, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31155899

RESUMO

INTRODUCTION: Mortality rates following hip arthroplasty range between 10% and 40% after 12 months. A higher rate is attributed to postoperative complications, of which surgical site infection is one of the most significant. In an effort to reduce surgical site infection following arthroplasty, antibiotics can be added to the cement used. The primary aim of this study was to determine whether dual antibiotic impregnated cement can reduce the rate of deep surgical site infection in patients following cemented arthroplasty for fractured neck of femur compared with single antibiotic impregnated cement. The secondary aim was to compare the rate of superficial surgical site infection in single compared with dual antibiotic cement. MATERIALS AND METHODS: A total of 206 patients were included. Group 1 included 108 retrospective patients who underwent arthroplasty for neck of femur fracture over a 12-month period using single antibiotic impregnated cement. Group 2 included 98 prospective patients who underwent arthroplasty for neck of femur fracture over a 12-month period using dual antibiotic impregnated cement. The rates of deep and superficial surgical site infection were investigated. RESULTS: Group 1 had a deep surgical site infection rate of 2.9% (n = 3), Group 2 had a deep surgical site infection rate of 0% (n = 0). Group 1 had a superficial surgical site infection rate of 3.7% (n = 4), Group 2 had a superficial surgical site infection rate of 5.1% (n = 5). CONCLUSION: Dual antibiotic cement reduced the rate of deep surgical site infection compared with conventional single antibiotic cement in arthroplasty for fractured neck of femur. Only a marginal difference in superficial surgical site infection was observed.


Assuntos
Antibacterianos/uso terapêutico , Artrite Infecciosa/epidemiologia , Artroplastia de Quadril/efeitos adversos , Cimentos para Ossos/uso terapêutico , Infecções Relacionadas à Prótese/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia/métodos , Artrite Infecciosa/etiologia , Artrite Infecciosa/prevenção & controle , Quimioterapia Combinada/métodos , Feminino , Fraturas do Colo Femoral/mortalidade , Fraturas do Colo Femoral/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/prevenção & controle , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Taxa de Sobrevida , Resultado do Tratamento
14.
Medicine (Baltimore) ; 98(25): e16074, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232945

RESUMO

The efficacy of sorafenib in combination with transarterial chemoembolization (TACE) or multiple-line therapies in patients with advanced hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the overall survival (OS) of patients with advanced HCC in response to different combination therapies.We analyzed the treatment and OS of 401 patients with Barcelona clinic liver cancer stage C HCC between 2012 and 2017. Mortality was analyzed using multivariate Cox regression, and OS was analyzed by the Kaplan-Meier method.The mean age was 59 years and males were predominant. During a median follow-up time of 8.6 months (range, 1-80 months), 346 (86.2%) patients died. In the multivariate Cox regression analysis, primary tumor size ≥5 cm, serum alpha-fetoprotein ≥200, and serum albumin ≥3.5 were significantly associated with mortality. In addition, compared with sorafenib alone, multiple-line treatments with sorafenib and multiple-line treatments without sorafenib yielded significantly decreased mortality. In the Kaplan-Meier analysis, sorafenib with TACE, multiple-line treatments with sorafenib, third-line treatments with sorafenib, and multiple-line treatments without sorafenib yielded a significantly better median OS than sorafenib alone.Sorafenib with concurrent multiple-line therapies significantly improved OS. These combination therapies will provide important information for immunotherapy combination with locoregional therapies in advanced HCC.


Assuntos
Quimioterapia Combinada/normas , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioembolização Terapêutica/métodos , Quimioembolização Terapêutica/normas , Quimioterapia Combinada/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Sorafenibe/uso terapêutico , Análise de Sobrevida , Taiwan , alfa-Fetoproteínas/análise
15.
PLoS Negl Trop Dis ; 13(6): e0007478, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31188821

RESUMO

BACKGROUND: Combination therapy with a third-generation cephalosporin (TGC) and a tetracycline analogue is recommended for Vibrio vulnificus infection. The combination of a TGC and ciprofloxacin has synergistic in vitro bactericidal activity against V. vulnificus. No clinical study has compared the standard regimen with TGC plus ciprofloxacin therapy for V. vulnificus infection. METHODS: Patients with a confirmed V. vulnificus infection at two medical centers in Korea from 1991 to 2016 were enrolled in this study. The patients were grouped according to the type of antibiotic administered. A retrospective propensity-score-matched case-control study of patients treated with TGC plus doxycycline or TGC plus ciprofloxacin was performed. The clinical characteristics and outcomes of the patients were analyzed. RESULTS: A total of 218 patients were confirmed to have V. vulnificus septicemia during the study, and the 30-day survival rate was 39% (85/218). The patients were classified into the following six treatment groups: TGC monotherapy (n = 82), TGC plus doxycycline therapy (n = 42), TGC plus ciprofloxacin therapy (n = 39), ciprofloxacin monotherapy (n = 14), other ß-lactam monotherapy (n = 10), and other (n = 31). The survival rates of these groups were as follows: TGC monotherapy (35%), TGC plus doxycycline (38%), TGC plus ciprofloxacin (54%), ciprofloxacin monotherapy (29%), other ß-lactam (20%), and other (39%). The 30-day survival rate showed no significant difference between the TGC plus doxycycline and TGC plus ciprofloxacin groups (log-rank test, P = 0.18). Among the 81 patients treated with TGC plus doxycycline or TGC plus ciprofloxacin, 12 per treatment group were selected by propensity-score matching. There was no significant difference in the baseline characteristics or the frequency of fasciotomy between the two groups. The 30-day survival rate showed no significant difference between the TGC plus doxycycline (50%) and TGC plus ciprofloxacin (67%) groups (log-rank test, P = 0.46). CONCLUSION: Our data suggest that the outcome of TGC plus ciprofloxacin therapy was comparable to that of TGC plus doxycycline therapy in patients with V. vulnificus septicemia.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Ciprofloxacino/uso terapêutico , Doxiciclina/uso terapêutico , Sepse/tratamento farmacológico , Vibrioses/tratamento farmacológico , Vibrio vulnificus/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Sepse/microbiologia , Resultado do Tratamento , Vibrioses/microbiologia , Vibrio vulnificus/efeitos dos fármacos , Adulto Jovem
16.
Drugs ; 79(10): 1135-1146, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31236801

RESUMO

Dapagliflozin (Forxiga®) is a highly potent, reversible and selective sodium-glucose cotransporter-2 inhibitor indicated worldwide for the treatment of type 2 diabetes (T2D). In the EU, oral dapagliflozin once daily is approved for use as monotherapy (in patients who are intolerant of metformin) and as add-on combination therapy (with other glucose-lowering agents, including insulin) for T2D when diet and exercise alone do not provide adequate glycaemic control. In numerous well-designed clinical studies and their extensions, dapagliflozin as monotherapy and combination therapy with other antihyperglycaemic agents provided effective glycaemic control and reduced bodyweight and blood pressure (BP) across a broad spectrum of patients. Dapagliflozin reduced the rate of cardiovascular (CV) death or hospitalization for heart failure (HHF), did not adversely affect major adverse CV events (MACE) and possibly reduced progression of renal disease relative to placebo in patients with established atherosclerotic CV disease (CVD) or multiple risk factors for CVD. Dapagliflozin was generally well tolerated, with a low risk of hypoglycaemia; diabetic ketoacidosis (DKA), although rare, and genital infections were more common with dapagliflozin than placebo. Given its antihyperglycaemic, cardioprotective and possibly renoprotective properties and generally favourable tolerability profile, dapagliflozin provides an important option for the management of a broad patient population, regardless of the history of CVD.


Assuntos
Compostos Benzidrílicos/farmacocinética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/farmacocinética , Hipoglicemiantes/farmacocinética , Inibidores do Transportador 2 de Sódio-Glicose/farmacocinética , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Aprovação de Drogas , Quimioterapia Combinada/métodos , Europa (Continente) , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/farmacologia , Gravidez , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Resultado do Tratamento
17.
J Urol ; 202(6): 1240-1247, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31188728

RESUMO

PURPOSE: Medications targeting androgen receptor activity (eg finasteride) or smooth muscle contractility (eg doxazosin) do not resolve lower urinary tract symptoms indicative of lower urinary tract dysfunction in an important subgroup of men. Recently fibrosis has been implicated as another pathobiology contributing to male lower urinary tract symptoms but to our knowledge no systematic studies have been done to assess fibrosis in the context of medical treatment. We determine whether fibrotic changes in the prostate transition zone are associated with an increased risk of clinical progression in participants treated with doxazosin, finasteride or finasteride plus doxazosin in the MTOPS (Medical Therapy of Prostatic Symptoms) study. MATERIALS AND METHODS: Transition zone biopsy tissues from men who did or did not experience clinical progression on placebo, doxazosin, finasteride or combination therapy were assessed for collagen content and architectural changes using picrosirius red birefringence and CT-FIRE (Curvelet Transform-Fiber Extraction) analysis. Correlations were made with annotated demographic and clinical data. Statistical analyses were done with the Pearson correlation coefficient, ANOVA and the t-test. RESULTS: High levels of wavy, aligned prostate transition zone collagen significantly correlated with an increased risk of clinical progression among MTOPS trial participants treated with doxazosin plus finasteride, particularly those with a high body mass index. CONCLUSIONS: Fibrotic changes in the prostate transition zone are associated with an increased risk of clinical progression in men treated with doxazosin plus finasteride. Antifibrotic therapeutics might provide a new treatment approach in men with lower urinary tract dysfunction who do not respond to current medical treatment approaches.


Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Próstata/patologia , Hiperplasia Prostática/tratamento farmacológico , Biópsia , Estudos de Coortes , Progressão da Doença , Doxazossina/uso terapêutico , Quimioterapia Combinada/métodos , Fibrose , Finasterida/uso terapêutico , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/complicações , Hiperplasia Prostática/patologia , Fatores de Tempo , Resultado do Tratamento
18.
Nat Commun ; 10(1): 2620, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197165

RESUMO

Conventional drug screens and treatments often ignore the underlying complexity of brain network dysfunctions, resulting in suboptimal outcomes. Here we ask whether we can correct abnormal functional connectivity of the entire brain by identifying and combining multiple neuromodulators that perturb connectivity in complementary ways. Our approach avoids the combinatorial complexity of screening all drug combinations. We develop a high-speed platform capable of imaging more than 15000 neurons in 50ms to map the entire brain functional connectivity in large numbers of vertebrates under many conditions. Screening a panel of drugs in a zebrafish model of human Dravet syndrome, we show that even drugs with related mechanisms of action can modulate functional connectivity in significantly different ways. By clustering connectivity fingerprints, we algorithmically select small subsets of complementary drugs and rapidly identify combinations that are significantly more effective at correcting abnormal networks and reducing spontaneous seizures than monotherapies, while minimizing behavioral side effects. Even at low concentrations, our polytherapy performs superior to individual drugs even at highest tolerated concentrations.


Assuntos
Epilepsias Mioclônicas/tratamento farmacológico , Modelos Biológicos , Rede Nervosa/efeitos dos fármacos , Fenômenos Fisiológicos do Sistema Nervoso/efeitos dos fármacos , Neurotransmissores/farmacologia , Algoritmos , Animais , Animais Geneticamente Modificados , Comportamento Animal/efeitos dos fármacos , Encéfalo/citologia , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/patologia , Ensaios de Triagem em Larga Escala/métodos , Humanos , Microscopia Confocal/métodos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Neurotransmissores/uso terapêutico , Peixe-Zebra
19.
Blood Coagul Fibrinolysis ; 30(4): 140-148, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31090596

RESUMO

: Uncontrolled bleeding due to trauma and coagulopathy is an area with high unmet medical need and high mortality rate. Treatment recommendations focus on transfusion of blood components while optimal therapy to improve coagulation remains to be established. The haemostatic effect of 2, 4 and 8 mg/kg recombinant prothrombin (MEDI8111) co-administered with 100 mg/kg fibrinogen (n = 7-8) was investigated in a porcine model of dilutional coagulopathy with uncontrolled bleeding. Vehicle (n = 11), fibrinogen alone (100  mg/kg , n = 15) were included as controls. Dilutional coagulopathy was induced by replacing ∼75% of the blood volume with hydroxyethyl starch and a standardized liver incision was made followed by intravenous administration of study compounds. Survival time and blood loss were determined up to 120 min after liver incision. Rotational thromboelastometry (ROTEM EXTEM), prothrombin time (PT), thrombin--antithrombin complex and thrombin generation were measured at baseline, after dilution and 10, 40, 80 and 120 min after compound administration. Administration of MEDI8111+fibrinogen improved haemostasis, decreased blood loss and dose-dependently improved survival time compared to fibrinogen. All pigs receiving a dose of 8 mg/kg MEDI8111+fibrinogen, which restored normal prothrombin concentration, survived to the end of the experiment with close to normal haemostasis as measured by PT and ROTEM EXTEM CT. Administration of fibrinogen and MEDI8111 was sufficient to improve survival time and haemostasis in severely coagulopathic pigs. The dose-dependent haemostatic improvement observed with MEDI8111 administration suggests that prothrombin concentration was rate limiting for coagulation.


Assuntos
Transtornos da Coagulação Sanguínea/tratamento farmacológico , Fibrinogênio/uso terapêutico , Hemorragia/prevenção & controle , Protrombina/uso terapêutico , Animais , Transtornos da Coagulação Sanguínea/complicações , Quimioterapia Combinada/métodos , Hemorragia/etiologia , Hemostasia/efeitos dos fármacos , Humanos , Proteínas Recombinantes , Análise de Sobrevida , Suínos , Fatores de Tempo
20.
Drugs ; 79(10): 1031-1036, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31134520

RESUMO

Glaucoma, a group of progressive optic neuropathies with similar patterns of tissue loss, is primarily treated with medical therapy, followed by laser therapy and, later, incisional surgery. Aside from the introduction of prostaglandin analogs, topical carbonic anhydrase inhibitors, and topical alpha-agonists in the 1990s, no new pharmaceutical agents to lower intraocular pressure (IOP) have been introduced for approximately 20 years. The Rho kinase inhibitors represent a new class of glaucoma medications that inhibit the downstream pathway of the Rho family of small G-proteins to increase outflow from the conventional (trabecular) outflow pathway in the eye. Several of these Rho kinase inhibitors, ripasudil and netarsudil, have recently reached the market and are used in clinical practice in several countries. A fixed-dose combination of latanoprost and netarsudil was also very recently approved (2019) by the US FDA. Several other novel agents are undergoing clinical trials. These drugs are poised to act as adjuncts to already established medical therapy for further lowering of IOP in the treatment of glaucoma.


Assuntos
Glaucoma/tratamento farmacológico , Inibidores de Proteínas Quinases/química , Quinases Associadas a rho/antagonistas & inibidores , Animais , Benzoatos/farmacologia , Quimioterapia Combinada/métodos , Olho , Humanos , Pressão Intraocular/efeitos dos fármacos , Isoquinolinas/farmacologia , Latanoprosta/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais , Sulfonamidas/farmacologia , beta-Alanina/análogos & derivados , beta-Alanina/farmacologia
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