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1.
Ann Pharmacother ; 55(1): 105-110, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618475

RESUMO

OBJECTIVE: To review the safety and efficacy of minocycline 4% topical foam for the treatment of moderate to severe acne vulgaris in adults and pediatric patients aged 9 years and older. DATA SOURCES: A literature search through PubMed and EMBASE was conducted using the following keywords: FMX101, minocycline, foam, and acne. STUDY SELECTION AND DATA EXTRACTION: Articles selected included those describing preclinical and clinical studies of pharmacokinetics, efficacy, or safety of topical minocycline foam. DATA SYNTHESIS: Minocycline 4% topical foam was shown in a preclinical study to effectively deliver minocycline to the pilosebaceous unit, with little penetration beyond the stratum corneum. This was consistent with a phase 1 pharmacokinetic study of the foam, which yielded a significantly reduced systemic exposure of minocycline compared with oral minocycline. In phase 2 and phase 3 clinical trials, the foam significantly reduced acne lesion counts and Investigator's Global Assessment scores of acne severity compared with placebo. The foam has a good safety profile, with headache, mild erythema, hyperpigmentation, and mild dryness among the most common adverse effects. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Topical antibiotics have been a mainstay of acne therapy with the benefit of less systemic exposure compared with oral antibiotics. However, the development of bacterial resistance has reduced their use, thereby reducing options for many patients with acne. Minocycline 4% topical foam is a safe and effective alternative, which may help restore this important therapeutic approach for treating acne vulgaris.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Minociclina/uso terapêutico , Administração Cutânea , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Criança , Ensaios Clínicos como Assunto , Feminino , Humanos , Hiperpigmentação/induzido quimicamente , Masculino , Minociclina/administração & dosagem , Minociclina/efeitos adversos , Resultado do Tratamento
2.
Zhonghua Nan Ke Xue ; 26(8): 726-730, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-33377735

RESUMO

Objective: To investigate the clinical value of the prostate small extracorporeal protein (PSEP) level in the urine in evaluating the therapeutic effect on chronic prostatitis (CP). METHODS: Totally 188 CP patients were treated with minocycline and Ningmitai Capsules in our hospital and regularly returned for follow-up examination from November 2017 to November 2018. Based on the results of treatment after 4 and 8 weeks of medication, we divided the patients into a cured, an effective and an ineffective group and compared the contents of PSEP in the urine samples of the three groups of patients before and after treatment. RESULTS: Compared with the baseline, the PSEP content in the urine after 4 weeks of medication was decreased in the cured group (n = 20) (ï¼»3.63 ± 3.81ï¼½ vs ï¼»1.16 ± 0.41ï¼½ ng/ml, P < 0.05), effective group (n = 85) (ï¼»4.13 ± 4.05ï¼½ vs ï¼»2.97 ± 2.89ï¼½ ng/ml, P > 0.05) and ineffective group (n = 83) (ï¼»4.72 ± 2.98ï¼½ vs ï¼»3.74 ± 1.31ï¼½ ng/ml, P > 0.05), and so was that after 8 weeks of treatment in the cured group (n = 48) (ï¼»3.72 ± 3.51ï¼½ vs ï¼»0.89 ± 0.37ï¼½ ng/ml, P < 0.05), effective group (n = 106) (ï¼»4.37 ± 3.93ï¼½ vs ï¼»1.83 ± 0.71ï¼½ ng/ml, P < 0.05) and ineffective group (n = 34) (ï¼»4.61 ± 3.59ï¼½ vs ï¼»3.58 ± 1.15ï¼½ ng/ml, P > 0.05). CONCLUSIONS: The PSEP level in the urine can be used as an index for clinical evaluation of the therapeutic effect on chronic prostatitis.


Assuntos
Prostatite , Proteínas/análise , Urinálise , Doença Crônica , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Masculino , Minociclina/uso terapêutico , Prostatite/tratamento farmacológico , Prostatite/urina
4.
PLoS Negl Trop Dis ; 14(9): e0008583, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32936818

RESUMO

BACKGROUND: Subclinical infection with Mycobacterium leprae is one potential source of leprosy transmission, and post-exposure prophylaxis (PEP) regimens have been proposed to control this source. Because PEP trials require considerable investment, we applied a sensitive variation of the kinetic mouse footpad (MFP) screening assay to aid in the choice of drugs and regimens for clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: Athymic nude mice were inoculated in the footpad (FP) with 6 x 103 viable M. leprae and treated by gastric gavage with a single dose of Rifampin (SDR), Rifampin + Ofloxacin + Minocycline (SD-ROM), or Rifapentine + Minocycline + Moxifloxacin (SD-PMM) or with the proposed PEP++ regimen of three once-monthly doses of Rifampin + Moxifloxacin (RM), Rifampin + Clarithromycin (RC), Rifapentine + Moxifloxacin (PM), or Rifapentine + Clarithromycin (PC). At various times post-treatment, DNA was purified from the FP, and M. leprae were enumerated by RLEP quantitative PCR. A regression analysis was calculated to determine the expected RLEP value if 99.9% of the bacilli were killed after the administration of each regimen. SDR and SD-ROM induced little growth delay in this highly susceptible murine model of subclinical infection. In contrast, SD-PMM delayed measurable M. leprae growth above the inoculum by 8 months. The four multi-dose regimens delayed bacterial growth for >9months post-treatment cessation. CONCLUSIONS/SIGNIFICANCE: The delay in discernable M. leprae growth post-treatment was an excellent indicator of drug efficacy for both early (3-4 months) and late (8-9 months) drug efficacy. Our data indicates that multi-dose PEP may be required to control infection in highly susceptible individuals with subclinical leprosy to prevent disease and decrease transmission.


Assuntos
Infecções Assintomáticas/terapia , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Mycobacterium leprae/efeitos dos fármacos , Profilaxia Pós-Exposição/métodos , Animais , Carga Bacteriana/efeitos dos fármacos , Claritromicina/uso terapêutico , Combinação de Medicamentos , Hanseníase/transmissão , Camundongos , Camundongos Nus , Minociclina/uso terapêutico , Moxifloxacina/uso terapêutico , Mycobacterium leprae/crescimento & desenvolvimento , Rifampina/análogos & derivados , Rifampina/uso terapêutico
5.
Rev. esp. cir. oral maxilofac ; 42(3): 139-142, jul.-sept. 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-196631

RESUMO

Actualmente las sustancias de relleno son la forma más popular para el rejuvenecimiento facial y el aumento de los tejidos. Existen varios problemas añadidos que han condicionado el aumento de las complicaciones con los materiales de relleno, que son el uso de sustancias adulteradas, la inyección de varios materiales en la misma zona o la administración por personal no entrenado/autorizado. Varias investigaciones sugieren que la ecografía de alta frecuencia (EAF) es una herramienta útil, de bajo coste y no invasiva para demostrar el tipo material de relleno e identificar el lugar de inyección y la cantidad de material inyectado. Presentamos en caso de una mujer de 64 años que presentaba edema hemifacial después de 15 años de haberse inyectado silicona líquida (SIL) en los labios, tratada con minociclina, mostrando mejoría clínica significativa


Currently injectable materials are popular for facial rejuvenation and soft tissue augmentation. There are some added problems, which have been conditioned by the increase in complications with fillers, that are the use of adulterated materials, injections of various types of substances in the same area or because administration by inexperienced/untrained professionals. Several studies suggest that high frequency ultrasound (HUS) is an economical, useful and non-invasive diagnostic tool to determine the nature and type of material and to identify the injection site and quantity of injected filler. We report a case of a 64-year-old woman who presented hemifacial swelling after 15 years of being injected with 1 infiltration of liquid injectable silicone (LIS) in the lips, treated with Minocycline, showing a significant clinical improvement


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Edema/diagnóstico por imagem , Silicones/efeitos adversos , Preenchedores Dérmicos/efeitos adversos , Assimetria Facial/etiologia , Próteses e Implantes/efeitos adversos , Prednisona/uso terapêutico , Minociclina/uso terapêutico
6.
Medicine (Baltimore) ; 99(34): e21751, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846799

RESUMO

INTRODUCTION: Chryseobacterium arthrosphaerae is a gram-negative bacteria, known for its intrinsic multidrug resistance, which can lead to treatment difficulties. PATIENT CONCERNS: A 56-year-old male had an indwelling external ventricular drainage catheter for 6 months and had been frequently treated with antibiotics for nosocomial infections. He showed cerebrospinal fluid pleocytosis and an abrupt fever during hospitalization. DIAGNOSIS: He was diagnosed as a ventriculitis caused by Chryseobacterium arthrosphaerae (C arthrosphaerae). INTERVENTION: Initially, we used ciprofloxacin as the backbone in combination with minocycline (and rifampin). However, fever and pleocytosis persisted, and improvement was slow. We then switched the minocycline and rifampin regiment to trimethoprim/sulfamethoxazole. Following this switch of antibiotics, the patient's pleocytosis rapidly improved, allowing the replacement of his external ventricular drainage catheters. C arthrospharae was no longer growing in cerebrospinal fluid and he was recovered from ventriculitis. OUTCOMES: The patient remains alive without any incidence of C arthrosphaerae recurrence. CONCLUSION: We propose trimethoprim/sulfamethoxazole alone or in combination with ciprofloxacin to be good candidates for the treatment of ventriculitis by C arthrosphaerae.


Assuntos
Antibacterianos/uso terapêutico , Ventriculite Cerebral/tratamento farmacológico , Chryseobacterium , Antibacterianos/administração & dosagem , Cateteres de Demora , Ventriculite Cerebral/complicações , Ventriculite Cerebral/diagnóstico , Drenagem , Quimioterapia Combinada , Humanos , Leucocitose/etiologia , Masculino , Pessoa de Meia-Idade , Minociclina/uso terapêutico , Rifampina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
8.
Expert Rev Anti Infect Ther ; 18(10): 997-1003, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32552044

RESUMO

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly grown into a public health emergency that has placed the national health systems as well as scientific research communities under enormous pressures. Drug repurposing or repositioning is a well-known strategy that seeks to deploy existing licensed drugs for newer indications and provides the quickest possible transition from bench to clinics for unmet therapeutic needs. Given the current, urgent, and dire need for effective therapies against novel coronavirus-19, this approach is particularly appealing. AREAS COVERED: Here, we review the significant anti-inflammatory, immunomodulatory, and antiviral properties of minocycline as potential mechanisms for efficacy against the novel coronavirus and highlight the promises and pitfalls of this approach. EXPERT OPINION: As compared to other agents being investigated for COVID-19, minocycline offers distinct advantages in terms of potential efficacy in patients with life-threatening acute respiratory distress syndrome (ARDS) and myocardial injury, well-known safety and interaction profile, relatively low costs, and widespread availability. We call upon public and private funders to facilitate urgent and rigorous research efforts before evidence-based recommendations for its widespread use can be made.


Assuntos
Antibacterianos/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Minociclina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Humanos , Pandemias
10.
Lancet Psychiatry ; 7(6): 515-527, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32445690

RESUMO

BACKGROUND: Several small studies suggest that the adjunctive use of anti-inflammatory agents might improve depressive symptoms in bipolar disorder. However, there are few well designed, appropriately powered clinical trials assessing the efficacy of these novel treatment strategies. We aimed to assess the efficacy of adjunctive minocycline or celecoxib in this setting. METHODS: This double-blind, 12-week, randomised, placebo-controlled trial was done in four outpatient psychiatric clinics in Pakistan. Eligible participants were adults (aged 18-65 years) with DSM-5 bipolar disorder (type I or II) and a major depressive episode. In a 2 × 2 factorial design, participants were randomly assigned (1:1:1:1) to receive either active minocycline plus active celecoxib, active minocycline plus placebo celecoxib, placebo minocycline plus active celecoxib, or placebo minocycline plus placebo celecoxib. The primary outcome was the mean change from baseline to week 12 in score on the 17-item Hamilton Depression Rating Scale (HAMD-17), assessed in all randomised participants (missing data were imputed and assumed to be missing at random). The trial was registered with ClinicalTrials.gov, NCT02703363. FINDINGS: 266 (17%) of 1542 patients assessed between May 1, 2016, and March 31, 2019, were randomly assigned to receive minocycline plus celecoxib (n=68), minocycline plus placebo (n=66), celecoxib plus placebo (n=66), or placebo plus placebo (n=66). From baseline to week 12, depressive symptoms as per HAMD-17 reduced in all four groups (from 24·5-25·2 to 11·3-12·8), but these reductions did not differ significantly between the groups. In terms of main effects, reductions in HAMD-17 did not differ for patients treated with minocycline (mean adjusted difference vs non-minocycline 1·48 [95% CI -0·41 to 3·36]; p=0·123) or for celecoxib (mean adjusted difference vs non-celecoxib -0·74 [-2·61 to 1·14]; p=0·443). Rates of serious adverse effects did not differ between groups (31 participants had a manic switch, two self-harmed, and one died in a motor vehicle accident). INTERPRETATION: We found no evidence that minocycline or celecoxib was superior to placebo for the treatment of bipolar depression. This large trial casts doubt on the potential therapeutic benefits of adjunctive anti-inflammatory drugs for the acute management of bipolar depression. FUNDING: Stanley Medical Research Institute.


Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Celecoxib/uso terapêutico , Minociclina/uso terapêutico , Adulto , Antibacterianos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Celecoxib/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minociclina/administração & dosagem , Paquistão/epidemiologia , Placebos/administração & dosagem , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
11.
Vet Microbiol ; 243: 108616, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32273002

RESUMO

This study examined the effect of minocycline alone and in combination with immunotherapy against pythiosis. Twenty rabbits, aged three months old and subcutaneously inoculated with Pythium insidiosum zoospores were divided into four groups (n = 5): treated with minocycline (10 mg/kg/day twice daily), treated with immunotherapy (34 mg subcutaneously every 14 days), treated with minocycline plus immunotherapy, and untreated (control group). The treatments were started 30 days after inoculation and continued for 70 days. The subcutaneous nodular injury areas in infected groups were measured every seven days after the beginning of treatment. Only the rabbits that developed lesions were selected for this study. When compared with the control group over 70 days, the minocycline and minocycline plus immunotherapy groups of rabbits with pythiosis showed significantly reduced injuries. The histopathology showed the presence of inflammation, macrophages and eosinophils. Grocott's staining revealed irregular hyphae-like structures that were ramified and occasionally septate. Our results suggest that minocycline has fungistatic activity and that the combination of minocycline and immunotherapy is more effective than the individual therapies tested.


Assuntos
Imunoterapia , Minociclina/uso terapêutico , Pitiose/tratamento farmacológico , Pitiose/terapia , Pythium/efeitos dos fármacos , Animais , Injeções Subcutâneas , Pitiose/imunologia , Coelhos
12.
Int J Infect Dis ; 96: 121-127, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32173573

RESUMO

OBJECTIVE: The aim of this study was to investigate the relationships between treatment outcomes of patients with urogenital Chlamydia trachomatis infections and minimum inhibitory concentrations (MICs) and drug resistance genes. METHODS: The clinical data of 92 patients diagnosed with Chlamydia trachomatis (C. trachomatis) infections were collected. Of these patients, 28 received regular treatment with azithromycin and 64 received minocycline. All patients underwent three monthly follow-ups after the completion of treatment. The microdilution method was used for the in vitro susceptibility tests. The acquisition of 23S rRNA mutations and presence of the tet(M) gene were detected by gene amplification and sequencing. RESULTS: The MICs of azithromycin, clarithromycin, erythromycin, tetracycline, doxycycline, and minocycline were comparable for isolates from the treatment failure and treatment success groups. Higher detection rates of 23S rRNA gene mutations and tet(M) were found in the treatment failure group (57.14% and 71.43%, respectively) than in the treatment success group (14.29% and 30.23%, respectively) (p < 0.05). The A2057G, C2452A, and T2611C gene mutations of 23S rRNA were detected in eight clinical isolates from the azithromycin treatment failure group, while the T2611C gene mutation was detected in one clinical strain from the treatment success group. CONCLUSIONS: The detection of resistance genes could better explain the high treatment failure rate than the MIC results in patients with urogenital C. trachomatis infections, highlighting the need for genetic antimicrobial resistance testing in infected patients.


Assuntos
Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/genética , Chlamydia trachomatis/isolamento & purificação , Feminino , Doenças dos Genitais Femininos/tratamento farmacológico , Doenças dos Genitais Femininos/microbiologia , Doenças dos Genitais Masculinos/tratamento farmacológico , Doenças dos Genitais Masculinos/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Minociclina/farmacologia , Minociclina/uso terapêutico , RNA Ribossômico 23S/genética , Falha de Tratamento , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Adulto Jovem
13.
Expert Opin Pharmacother ; 21(7): 741-746, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32037906

RESUMO

INTRODUCTION: Oral minocycline is a mainstay of therapy for moderate-to-severe acne; however, systemic side effects which include hepatotoxicity, lupus-like syndrome, drug hypersensitivity syndrome, autoimmune hepatitis, polyarteritis nodosa, gastrointestinal side effects and skin hyperpigmentation are of concern. Topical antibiotics commonly used in acne, such as erythromycin and clindamycin, present high P. acnes resistance rates which has opened the market for new topical antibiotics. FMX-101 is a novel topical minocycline foam that has shown promising results in phase I, II and III trials for the treatment of moderate-to-severe acne with a better safety profile than oral minocycline. AREAS COVERED: The author provides an overview FMX-101 including its clinical efficacy and safety. The author then provides their expert opinion on this treatment and its potential for the treatment option for acne. EXPERT OPINION: The topical foam formulation of FMX-101 has been shown to reduce both inflammatory and non-inflammatory lesions and to improve IGA scores in patients with moderate-to-severe acne without significant systemic absorption thus limiting associated side effects. Overall, the proven efficacy and safety profile of FMX-101, together with the low systemic absorption, high skin tolerability and cosmetically acceptable foam formulations render this novel therapy an important addition to the acne treatment armamentarium.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Minociclina/uso terapêutico , Administração Cutânea , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Minociclina/administração & dosagem , Minociclina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento
14.
Arch Biochem Biophys ; 682: 108302, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32057758

RESUMO

There is currently no effective treatment for neurological impairment caused by traumatic brain injury (TBI). It has been reported that excessive iron production in the brain may be a key factor in neurological impairment. In the present study, we investigated the effects of minocycline, a semi-synthetic tetracycline antibiotic, against TBI-induced neurological impairment and explored its underlying mechanism. Neurological impairment was assessed by foot-fault test, cylinder test, wire hang test, and Morris water maze. Nissl staining was performed to evaluate cell viability in the brain. The iron concentrations in cerebrospinal fluid (CSF), serum, and brain tissues were examined. The Fe2+- and Fe3+- chelating activity of minocycline was measured. Finally, the expression levels of important iron metabolism proteins ferritin, transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1), and hepcidin in the hippocampus and cortex were measured by Western blot analysis. The results indicate that minocycline significantly attenuated the neurological impairment caused by TBI and increased neuronal viability. Minocycline showed a Fe2+- and Fe3+- chelating activity in vitro and reduced the iron concentration in CSF and brain tissues (cortex and hippocampus). Minocycline also inhibited the overexpression of ferritin and TfR1, but did not affect the expression of DMT1. Minocycline restored the expression of FPN1 by decreasing the expression of hepcidin. In conclusion, minocycline may attenuate neurological impairment caused by TBI and regulate iron metabolism.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Ferro/metabolismo , Minociclina/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Córtex Cerebral/metabolismo , Quelantes/farmacologia , Modelos Animais de Doenças , Ferritinas/metabolismo , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto , Doenças do Sistema Nervoso/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores da Transferrina/metabolismo , Tetraciclina/farmacologia
15.
BMC Infect Dis ; 20(1): 62, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959113

RESUMO

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase Multibacilar/tratamento farmacológico , Hanseníase Paucibacilar/tratamento farmacológico , Minociclina/uso terapêutico , Ofloxacino/uso terapêutico , Rifampina/uso terapêutico , Organização Mundial da Saúde , Adolescente , Adulto , Idoso , Criança , Protocolos Clínicos , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Hansenostáticos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Minociclina/efeitos adversos , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/isolamento & purificação , Doenças Negligenciadas/tratamento farmacológico , Ofloxacino/efeitos adversos , Recidiva , Rifampina/efeitos adversos , Falha de Tratamento , Adulto Jovem
16.
JAMA Neurol ; 77(2): 164-174, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31738372

RESUMO

Importance: There are no disease-modifying treatments for Alzheimer disease (AD), the most common cause of dementia. Minocycline is anti-inflammatory, protects against the toxic effects of ß-amyloid in vitro and in animal models of AD, and is a credible repurposed treatment candidate. Objective: To determine whether 24 months of minocycline treatment can modify cognitive and functional decline in patients with mild AD. Design, Setting, and Participants: Participants were recruited into a double-blind randomized clinical trial from May 23, 2014, to April 14, 2016, with 24 months of treatment and follow-up. This multicenter study in England and Scotland involved 32 National Health Service memory clinics within secondary specialist services for people with dementia. From 886 screened patients, 554 patients with a diagnosis of mild AD (Standardised Mini-Mental State Examination [sMMSE] score ≥24) were randomized. Interventions: Participants were randomly allocated 1:1:1 in a semifactorial design to receive minocycline (400 mg/d or 200 mg/d) or placebo for 24 months. Main Outcomes and Measures: Primary outcome measures were decrease in sMMSE score and Bristol Activities of Daily Living Scale (BADLS), analyzed by intention-to-treat repeated-measures regression. Results: Of 544 eligible participants (241 women and 303 men), the mean (SD) age was 74.3 (8.2) years, and the mean (SD) sMMSE score was 26.4 (1.9). Fewer participants completed 400-mg minocycline hydrochloride treatment (28.8% [53 of 184]) than 200-mg minocycline treatment (61.9% [112 of 181]) or placebo (63.7% [114 of 179]; P < .001), mainly because of gastrointestinal symptoms (42 in the 400-mg group, 15 in the 200-mg group, and 10 in the placebo group; P < .001), dermatologic adverse effects (10 in the 400-mg group, 5 in the 200-mg group, and 1 in the placebo group; P = .02), and dizziness (14 in the 400-mg group, 3 in the 200-mg group, and 1 in the placebo group; P = .01). Assessment rates were lower in the 400-mg group: 68.4% (119 of 174 expected) for sMMSE at 24 months compared with 81.8% (144 of 176) for the 200-mg group and 83.8% (140 of 167) for the placebo group. Decrease in sMMSE scores over 24 months in the combined minocycline group was similar to that in the placebo group (4.1 vs 4.3 points). The combined minocycline group had mean sMMSE scores 0.1 points higher than the placebo group (95% CI, -1.1 to 1.2; P = .90). The decrease in mean sMMSE scores was less in the 400-mg group than in the 200-mg group (3.3 vs 4.7 points; treatment effect = 1.2; 95% CI, -0.1 to 2.5; P = .08). Worsening of BADLS scores over 24 months was similar in all groups: 5.7 in the 400-mg group, 6.6 in the 200-mg group, and 6.2 in the placebo groups (treatment effect for minocycline vs placebo = -0.53; 95% CI, -2.4 to 1.3; P = .57; treatment effect for 400 mg vs 200 mg of minocycline = -0.31; 95% CI, -0.2 to 1.8; P = .77). Results were similar in different patient subgroups and in sensitivity analyses adjusting for missing data. Conclusions and Relevance: Minocycline did not delay the progress of cognitive or functional impairment in people with mild AD during a 2-year period. This study also found that 400 mg of minocycline is poorly tolerated in this population. Trial Registration: isrctn.org Identifier: ISRCTN16105064.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Minociclina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Minociclina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Resultado do Tratamento
17.
Int J Radiat Oncol Biol Phys ; 106(1): 100-107, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31627177

RESUMO

PURPOSE: In patients with non-small cell lung cancer (NSCLC), concurrent chemoradiation therapy (CRT) exacerbates a cluster of difficult-to-manage symptoms, especially cancer-related fatigue. Minocycline is a readily available, low-cost antibiotic with antiinflammatory properties. We conducted a phase 2 randomized, double-blinded, placebo-controlled trial to investigate the effect of minocycline in reducing CRT-symptom burden in NSCLC. METHODS AND MATERIALS: Patients with NSCLC scheduled to receive CRT provided consent and were randomized to receive either minocycline (100 mg twice daily) or a matching placebo during 6 to 7 weeks of CRT. Patient-reported fatigue and other symptoms were assessed on MD Anderson Symptom Inventory weekly from the start of CRT for 12 weeks. The primary outcome was 12-week (±2 days) area under the curve for symptom burden, which was compared between treatment groups. RESULTS: Forty of 49 enrolled patients (80%) were evaluable (19 on minocycline and 21 on placebo). There were no grade 3 + adverse events related to the study medication. Fatigue was significantly reduced in the minocycline group compared with placebo group during the 12-week trial period (area under the curve = 31.2 ± 14.2 vs 45.0 ± 20.9, P = .011), with a large effect size (Cohen's d = 0.77). Pain (Cohen's d = 0.54) and shortness of breath (Cohen's d = 0.55) were also significantly reduced in the minocycline group (all P < .05). CONCLUSIONS: Minocycline during CRT for NSCLC was feasible, had a low toxicity profile, and yielded a clinically and statistically significant positive signal in reducing symptom burden related to NSCLC and CRT. This study is a proof of concept so a larger trial in CRT patients is warranted.


Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimiorradioterapia/efeitos adversos , Fadiga/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Minociclina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma Pulmonar de Células não Pequenas/complicações , Método Duplo-Cego , Dispneia/tratamento farmacológico , Fadiga/etiologia , Feminino , Humanos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Estudos Prospectivos , Qualidade de Vida
18.
Support Care Cancer ; 28(1): 261-269, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31037378

RESUMO

PURPOSE: Local/systemic symptoms during cancer therapy may be exacerbated by dysregulated inflammation and its downstream toxic effects. Minocycline can suppress proinflammatory cytokine release; therefore, we investigated its potential to reduce patient-reported symptom severity during radiotherapy (RT) for head and neck cancer (HNC). METHODS: Eligible patients for this blinded, placebo-controlled trial were adults with T0-3, N-any, and M0 HNC receiving single-modality RT. Participants were randomized 1:1 to either minocycline (200 mg/day) or placebo during RT. The primary endpoint was the area under the curve (AUC) of 5 prespecified symptoms (pain, fatigue, disturbed sleep, poor appetite, difficulty swallowing/chewing) during RT, assessed with the MD Anderson Symptom Inventory for HNC (MDASI-HN). RESULTS: We analyzed data from 20 evaluable patients per arm. Overall, 75% had oropharyngeal cancer and 78% were male. No grade 3+ adverse events potentially related to study medication were observed. Two minocycline patients required a feeding tube during RT vs 5 placebo patients (P = 0.21). The average daily AUC during RT for the 5 MDASI-HN symptoms was 3.1 (SD = 1.0) for minocycline and 3.7 (SD = 1.7) for placebo (P = 0.16); the 0.37 effect size was less than our 0.70 target. AUC comparisons for several individual symptoms and symptom interference favored minocycline but were not statistically significant. The greatest numerical differences occurred for systemic symptoms, larger toward treatment end, and in early post-RT recovery. CONCLUSIONS: Minocycline was feasible, well tolerated, and achieved a positive signal toward reducing patient-reported symptom severity during RT for HNC, particularly for systemic symptoms. This justifies additional study and informs future trial design.


Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Minociclina/uso terapêutico , Radiodermatite/prevenção & controle , Idoso , Terapia Combinada , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Dor/epidemiologia , Dor/etiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Resultado do Tratamento
19.
J Am Acad Dermatol ; 82(4): 832-837, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31163231

RESUMO

BACKGROUND: FMX101 4% topical minocycline foam has been shown to be an effective and safe treatment for acne vulgaris (AV). OBJECTIVE: To further evaluate the efficacy and safety of FMX101 4% in treating moderate to severe acne vulgaris. METHODS: A 12-week, multicenter, randomized (1:1), double-blind, vehicle-controlled study was conducted. Coprimary end points were the absolute change in inflammatory lesion count from baseline and the rate of treatment success (Investigator's Global Assessment score of 0 or 1 with a ≥2-grade improvement). RESULTS: There were 1488 participants in the intent-to-treat population. The FMX101 4% group had significantly greater reductions in the number of inflammatory lesions from baseline (P < .0001) and a greater rate of treatment success based on Investigator's Global Assessment (P < .0001) versus the foam vehicle group at week 12. FMX101 4% was generally safe and well tolerated. LIMITATIONS: The efficacy and safety of FMX101 4% were not characterized in participants with mild AV. CONCLUSION: FMX101 4% topical minocycline foam was effective and safe for the treatment of moderate to severe AV.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Dermatoses Faciais/tratamento farmacológico , Minociclina/uso terapêutico , Administração Cutânea , Adolescente , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Minociclina/administração & dosagem , Minociclina/efeitos adversos , Resultado do Tratamento , Adulto Jovem
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